Micro 3

Most common cause of wound infections in Iraqui war veterans

"Iraquibacter" = Acinetobacter baumannii

Febrile episode of Relapsing Fever ends with

"crisis" = very high fever, delirium, rapid heartbeat & respiration, when drenching sweat & chills - epidermic, borrelia recurrentis via body lice - endemic, b. hermsii, b. parkerii, & b. turicatae via soft ticks

(TEST): A sexually active premenopausal female seeks evaluation for a vaginal discharge. Pelvic exam reveals a scant grey discharge, normal vulva and vagina, with no discharge noted from the cervical os. Saline preparation of the discharge reveals an elevated pH (greater than pH 4.5), with "clue cells" seen on microscopic visualization. Addition of KOH to the saline preparation releases an amine odor. The most likely diagnosis is

*Bacterial vaginosis*

(TEST): Which of the following correctly describes sulfa-trimethoprim?

*Bactericidal in urine, but bacteriostatic in tissue infections* - only bacteriosttic if used for tissue infections because bacteria acquire some metabolites that they cannot synthesize

Treatment of Helicobacter

Antibiotics (1-2 weeks) - *tetracycline, metronidazole*, ampicillin Omeprazole *Bismuth salts (Pepto-Bismol)* *Multiple studies have showed that treatment with combos of bismuth salts, Metronidazole, ampicillin, &/or tetracycline clears H. pylori & results in dramatic decrease in both duodenal & gastric ulcer recurrence*

(TEST): The state Department of Health was recently called in to investigate an outbreak of bacterial infections in a regional hospital. The initial infection appeared to occur in an intensive care unit and quickly spread throughout the hospital. Which one of the following was likely identified as the cause?

Acinetobacter baumannii

Virulence factors of V. vulnificus

Antiphagocytic polysaccharide capsule Cytolysins Collagenase Protease Siderophores - raw oysters, contaminated shellfish, wound infections - swimming in ocean

Roundworm likely to be transmitted by ingestion of food or water contaminated with feces

Ascaris lumbricoides - transmitted via fecal-oral route

(TEST): Which antibiotic is often used to treat respiratory infections and is part of the CDC-recommended combined antibiotic regimen for treating gonorrhea?

Azithromycin

Treatment of Mycoplasma

Azithromycin, Doxycycline, Levofloxacin - resistance to macrolides reported - Eythromycin used in children Clindamycin for M. hominis, M. genitalium - resistance to erythromycin, doxycycline

Most common Burkholderia species

B. cepacia - actually a complex of at least 18 species - hard to differentiate so collectively called the *B. cepacia Complex (BCC)* - found in soil & water BCC - major cause of pneumonia in CF patients or patients with chronic granulomatous disease - can co-infect CF lung with P. aeruginosa = *very poor prognosis* for CF patients (more deadly then P. aeruginosa) - presence is contraindicated for lung patient (waste of transplant)

Presence of what bacteria is contraindicated in CF patients for lung transplant?

B. cepacia Complex (BCC) - can invade macrophages in lung - produces proteases

E. coli diseases

Bacteremia/Septicemia UTI Gastroenteritis Hemorrhagic colitis Hemolytic uremic syndrome (HUS) *Neonatal meningitis* Intraabdominal infections - associated with intestinal perforation

Most common vaginal infection in women of childbearing age

Bacterial Vaginosis - common in pregnant women - risk increased by douching, new sex partners, multiple sexual partners - *not sexually transmitted*

Change in normal flora form lactobacillus dominated community to increased number of anaerobes

Bacterial Vaginosis - increases vaginal pH

Encodes genes for 2 subunits of *cholera toxin in V. cholerae*

Bacteriophage CTXφ - ctxA & ctxB - binds to *toxin co-regulated pilus* (tcp) & moves into bacterium - after internalization, it becomes integrated into bacterial genome - encodes other virulence genes = *accessory cholera enterotoxin gene* ace; *zonnula occludens toxin* gene zot; coordinated by regulatory genes (ToxR regulator)

To maintain growth in the lab, microorganisms require optimal growth conditions mimicking their natural environments; such as temperature, maintained in incubators & atmosphere, accomplished sometimes by the use of candle jar which elevate the levels of which gas?

CO2

(TEST): A food-borne gram-negative bacillus,commonly transmitted via contaminated or improperly cooked poultry, that causes the production of a green and extremely foul-smelling diarrhea is

Campylobacter

(TEST): A food-borne, Gram-negative bacillus that is commonly transmitted via contaminated or improperly cooked poultry and causes the production of a green and extremely foul-smelling diarrhea is

Campylobacter

(TEST): Which food-borne, gram-negative bacillus is commonly found in contaminated or improperly cooked poultry and produces a watery, green-colored, foul-smelling diarrhea?

Campylobacter - wild & domestic aniamls, poultry - fecal-oral route - can also be acquired via unpasteurized milk

(TEST): Guillain-Barré Syndrome (GBS) has been linked to which of the following causes of gastrointestinal disease

Campylobacter species

Treatment for UTIs caused by E. coli

Cephalosporins Sulfa-trimethoprim/Sulfamethoxazole sometimes nalidixic acid Tetracycline - resistance to amoxicillin increasing - treatment for diarrhea or hemorrhagic colitis = controversy for the use of antibiotics - may recover without - treatment for HUS = IV fluids & nutritional supplementation, blood transfusions maybe, dialysis (short-term) - more than 85% of patients with most common form of HUS recover complete kidney function

Proteus treatment: parenteral therapy for catheter-related UTIs

Cephalosporins Ticarcillin-Clavulanate (Timentin) Piperacillin-Tazobactam (Zosyn)

Fastidious, Gram-negative, facultative anaerobic coccobacillus. Global incidence 6 million cases in Africa, Southeast Asia, and Caribbean region, only sporadic in USA. Tender, *erythematous papule* in 2-14 days. Ruptures in 2-3 days to form *painful ulcer with soft edges*. Swelling *inguinal lymph nodes (bubos)*.

Chancroid - Haemophilus ducreyi - treatment = *azithromycin* or ceftriaxone or alternative ciprofloxacin or erythromycin

(TEST): You have a patient who has a urinary catheter placed 48 hours ago, but who is otherwise healthy. He develops a urinary tract infection, and laboratory tests indicate that the infecting organism produces urease and exhibits swarming motility. What would be the best course of treatment for this patient?

Change his catheter & administer sulfa-trimethoprim or ciprofloxacin

The pathogen was isolated on MacConkey Agar from a patient's blood sample & seen to utilize lactose; further testing revealed that the organism did not produce indole as a byproduct.

*Klebsiella* - NDM-1: metallo-beta-lactamase-1 = resistance to braod range of beta lactamse - endemic in Vietnam - Donovan bodies = small rods in PMNs - granulomatous lesions - copious, mucoid capsule - TSI: acid over acid & gas - causes typical pneumonia

(TEST) NDM-1 beta-lactamase was first discovered in this pathogen

*Klebsiella* - endemic in Vietnam - Donovan bodies - granulomatous lesions - copious, mucoid capsule

(TEST): Infection with which ONE of these organisms is associated with hematuria, the presence of blood in the urine?

*Schistosoma hematobium* / blood fluke - second to malaria as cause of sickness in tropics - found in freshwater - penetrate skin --> invade venous system --> mate & lay eggs - eggs may enter lumen of intestine or bladder --> may be excreted via feces or urine into nearby stream or lake so they can continue life cycle

(TEST): This large intestinal ciliate is associated with hog and guinea pig farmers and causes dysentery and colitis.

*Balantidium coli* = giant ciliate - trophozoite (loose stools) - cyst (thick-resistant wall; cilia inside; kidney bean macronucleus; formed stools) - pigs = common reservoir host - most cases are asymptomatic - *Balantidial Dysentery or Colitis* - diagnosis = stool exam for cysts & trophs - treatment = *tetracycline* - largest parasitic protozoans found in intestine

(TEST): These blood-sucking arthropods are not known to transmit any disease

*Bed bugs*

(TEST): Treatment for acute Chagas disease

*Benznidazole* Chagas Disease - via Trypnasoma cruzi - the Americas - animal reservoirs: amerdillos, rodents, opossums - vector = reduviid bug/kissing bug = feeds on humans while they sleep & defecates while it eats - chronic = megacolon, electrical arrhythmias, dilatation of heart

(TEST): Which one of the following Gram-negative bacteria is often the cause of brain abscesses in neonates and is transmitted nosocomially or vertically (from mother to fetus)?

*Citrobacter koseri* - sepsis, meningitis, brain abscesses in neonates - nosocomial or vertical (mother to fetus) transmission

(TEST) bacterial common cause of neonatal sepsis, meningitis, brain abscesses acquired via vertical transmission (mother to fetus in utero)

*Citrobacter* = nosocomial or vertical transmission - treatment = penicillin or 3rd generation cephalosporin + aminoglycoside

E. coli associated with bloody diarrhea

*Enterohemorrhagic (EHEC)* - secrete Shig-like toxin / verotoxin - inhibit protein synthesis by inhibiting 60S ribosome = intestinal epithelial cell death - *bloody* (hemorrhagic) diarrhea, accompanied by abdominal cramps = hemorrhagic colitis - HUS

E. coli associated with Bacillary dysentery (extreme cramping, blood, pus, high fevers)

*Enteroinvasive (EIEC)* - microbe invades intestinal mucosa & causes necrosis & inflammation - *i*nvasive - dystenery - clinical manifestations similar to Shigella

Ureaplasma species: non-gonococcal urethritis. endometriosis. pre-term birth.

*U. urealyticum* - part of normal flora in 60% of healthy sexually active women - commonly infects lower urinary tract = urethritis = burning on urination (dysuria) & sometimes yellow mucoid discharge from urethra - can be identified by ability to metabolize urea into ammonia & CO2 - treatment = erythromycin, tetracycline

Mycoplasma pneumonia/Atypical pneumonia causes both

*Upper respiratory infections* - *tracheobronchitis* = most common (especially children)= bronchial passages infiltrated with lymphocytes & plasma cells can occur - pharyngitis = sore throat - otitis media = non-purulent *Lower respiratory infections* (5-10%) - primary atypical pneumonia - *walking pneumonia* - mild but lasting both present as *persistent, dry cough*

Complication related to aklaline pH created by urease of Proteus

*Urinary stones --> Urinary Crystalization* - transmitted via catheters - produces powerful ureas --> hydrolyzes urea to ammonia & CO2 = struvite kidney stones = urinary tract obstruction

Most common cause of GI disease in Japan & Southeast Asia. Most common vibrio species causing GI disease in U.S.

*V. parahaemolyticus* - shellfish, seawater - gastroenteritis, wound infection, bacteremia - self-limited diarrhea to *mild* cholera-like disease - symptoms = 5-72 hours after ingestion: explosive, watery diarrhea - then: headache, abdominal cramps, nausea, vomiting, low-grade fever for 3 or more days - uneventful recovery - wound infections can occur if people exposed to contaminated seawater

Diseases caused by Chlamydia trachomatis Serogroups D-K (G- pleomorphic bacteria).

Chlamydia Trachoma (conjunctivitis)

Vibrio capsule produced by

*V. vulnificus & non-O1 V. cholerae* - helps disseminate infection - not produced by V. cholerae O1 (bacteria don't spread beyond intestine)

Vibrio species responsible for severe wound infections and high fatality

*V. vulnificus* - shellfish, seawater - bacteremia, wound infection, cellulitis - wound infections after contaminated seawater - swelling, erythema, pain - development of vesicles or bullae - tissue necrosis - fever & chills - mortality in 50% untreated - septicemia after consumption of contaminated raw oysters, especially in middle of summer

Treatment of Rickettsia rickettsii: RMSF

*doxycycline* for 7-14 days alternative = chloramphenicol - do not wait for confirmation before beginning treatment!!! - treat base don clinical suspicion via mortality of RMSF pic = Giminez stain of tick hemolymph cells infected with R. rickettsii

Rickettsia, Orientia, Coxiella, Ehrlichia, & Anaplsma are all small aerobic bacteria that can be inhibited by

*doxycycline*, tetracycline, chloramphenicol

Treatment for Scrub Typhus: Orientia tsutsugamushi

*doxycyline* alternatives = chloramphenicol, rifampin azithromycin for children & pregnant women Scrub Typhus / Tsutsugamushi Fever - Asia, Southwest Pacific - affected soldiers in South Pacific during WWII & in Vietnam - spread by *bite of larvae (chiggers) of mties - mites live on rodents --> larval chiggers live in soil - after 2 week incubation period = high fever, headache, scab at original bite site - later: flat & sometimes bumpy (maculopapular) rash develops

(TEST): Community-acquired Legionella pneumophila infections tend to have a peak seasonal occurrence. This is most likely due to

*elevated surface-water temperature* Legionella pneumophila - ubiquitous in natural & manmade water environments - disruption of biofilm can = massive release of Legionella in water

(TEST): A secondary complication of Mycoplasma or atypical pneumonia is

*erythema multiforme or mucocutaneous eruptions* - associated with infections (Mycoplasma pneumonia, HSV), drugs, cancers, autoimmune disease - presents with multiple types of lesions - macules, papules, vesicles, target lesions (looks like targets with multiple rings & dusky center showing epithelial disruptions)

B. melitensis associated with what animals?*

*goats & sheep* Brucella - coccobacilli - non-motile - aerobes - facultative intracellular - zoonotic - direct contact with animals - contaminated milk or animal tissue - inhalation - smooth colonies are virulent - virB operon activated in phagolysosome - treatment = doxycycline & rifampin

Leading cause of infertility in women

Chlamydia trachomatis

(TEST): Penicillins are used to treat most anaerobic bacterial infections, but are less effective for anaerobic

*gram-negative rods such as Bacteroides fragilis* Bacteroides fragilis - doesn't contain lipid A in its outer cell membrane (no endotoxin) - following abdominal surgery, antibiotics that cover anaerobes are given as prophylaxis against B. fragilis = clindamycin, metronidazole/Flagyl, chloramphenicol

Principal symptoms of tertiary syphilis

*gummas (skin, bone, heart), neurosyphilis* Tertiary syphilis - develops over 6-40 years - gummatous syphilis occurs 3-10 years after primary infection in 15% of untreated patients - cardiovascular syphilis occurs at least 1 years after primary infection in 10% untreated - neurosyphilis: subacute meningitis, meningovasculas syphilis, tabes dorsalid, Argyll-Robertson pupil

(TEST): Cytotoxic strains of Pseudomonas aeruginosa use an injectisome to inject ExoU into target cells. This molecule

*has lipase activity, which quickly kills the cell* ExoS - ADP-ribosylates early host proteins: ezrin, radixin, moesin proteins (ERMs) ExoT - ADP-ribosylates Crk protein --> inactivation of Rac --> no wound healing ExoY - adenylate cyclase --> increased cAMP --> disrupts cell shaped --> homoserine lactone production

(TEST): Pseudomonas aeruginosa has a large genome and its gene expression is regulated by several mechanisms. The lasR and lasI genes participate in a regulatory system that involves the synthesis and secretion of a small molecule whose accumulation causes a change in Pseudomonas gene expression. This secreted regulatory molecule is

*homoserine lactone*

(TEST): A patient with a large abdominal surgical wound develops a fever, and pus appears on sutures of his wound. A Gram stain of the pus shows organisms typical of Bacteroides and Fusobacterium. The patient is treated with ampicillin and gentamicin. This therapy is

*inappropriate; change to a different drug or drugs* Bacteroides = need drugs that cover anaerobes - clindamycin - metronidazole / Flagyl - chloramphenicol

(TEST): A 3-year-old girl developed pneumonia and the lab data indicate that it may be due to Chlamydia. The physician prescribed doxycycline for this infection. This therapy is

*inappropriate; change to another therapy* - treatment = doxycycline, macrolide, or a fluroquinolone BUT doxycycline is contraindicated in children

(TEST): Ventilator-associated pneumonia caused by Acinetobacter baumannii is a major concern due to

*increased antibiotic resistance*

Infection of humans with Coxiella burnetii, Q fever agent usually via

*inhalation of organisms* - airborne barnyard dust containing aerosolized bcteria Q fever - no arthropod vector - spores inhaled as aerosols from cattle/sheep amniotic fluid - presents as pneumonia - most common cause of culture negative endocarditis - causative agent can survive outside in its endospore form

Invasion of Neisseria meningitidis into host via

*nasopharyngeal mucosal epithelium* - first *must be colonized before show clinical symptoms* - nasopharyngeal colonization = prerequisite for systemic infection - use virulence factors to adhere, invade, & evade host defenses

(TEST): Long term prophylaxis for urinary tract infections frequently involves

*nitrofurantoin* - causes bacterial DNA damage - bacteriostatic - concentrated in urine = used solely as urinary tract antiseptic against E. coli

(TEST): A patient presents with intractable sinusitis which has failed to respond to multiple rounds of antibiotics. The patient has a history of allergic rhinitis, asthma, and nasal polyps. The patient is otherwise healthy with a normal immune system. The most likely diagnosis in this patient is

*non-invasive sinusitis*

(TEST): Phaeohyphomycoses are infections caused by the dematiaceous, or black, molds containing melanin in their cell wall. These have typically been associated with allergic fungal sinusitis, brain abscess, and, in rare outbreaks associated with contaminated steroid solutions prepared by a compounding pharmacy, meningitis. Such infections would be considered

*opportunistic* Dematiaceous septate hyphae = blackwall fungi Phaeohyphomycosis - infections caused by dematiaceous/black mold containing melaning in its cell wall dark - associated with allergic fungal sinusitis, brain abscess - treatment = surgical drainage or excision - *amphotericin B* for epidural or brain abscesses - *itraconazole* long-term for sinusitis - *voriconazole* for meningitis

(TEST): Phaeohyphomycoses are infections caused by the dematiaceous (black) molds containing melanin in their cell wall. These are typically associated with allergic fungal sinusitis, brain abscess, and rare outbreaks of meningitis. A recent outbreak linked contaminated steroid solutions prepared by a compounding pharmacy would be considered

*opportunistic* Phaeohyphomycoses - infections causes by dematiaceous/black mold containing melanin in its cell wall - associted with allergic fungal sinusitis, brain abscess - Bipolaris, Curvularia, Exophiala, Cladosporium, Phialophora, Laternaria, Exserohilum rostratum - Amphotericin B for epidural or brain abscesses, itraconazole long term for sinusitis, voriconazole for meningitis

(TEST): The lesion from a Haemophilus ducreyi infection called chancroid is best described as a

*painful genital ulcer* Haemophilus ducreyi = Factor X = STD: chancroid - painful genital ulcer - unilateral painful swollen inguinal lymph nodes rapidly develop in half of infected ppl - lymph nodes become matter & will rupture treatment = azithromycin or ceftriaxone or alternative ciprofloxacine or erythromycin

Treatment for Syphilis

*penicillin*, tet, eryth

Eikenella corrodens usually susceptible to

*penicillin, ampicillin, cephalosporins, tetracyclines, fluroquinolones* FAT PC Eikenella corrodens - non-spore forming rod - facultative anaerobe - colonizes human oropharynex - human bite wounds or fist fite injuries - opportunistic - *subacute endocarditis* (HAC*E*K) - sinusitis, meningitis, brain & lung abscesses, pneumo

Kingella kingae usually susceptible to

*penicillin, tetracyclines, erythromycin, fluoroquinolones, & aminoglycosides* (FATE P) Kingella kingae - colonizes throats of young children - causes septic arthrtis & osteomyelitis in children - in children & adults: causes endocarditis of native & prosthetic valves

B. suis associated what animals?

*pigs* Brucella suis... - gram-negative, facultative, intracellular coccobacillus - capable of growing in phagocytic cells

Optochin test differentiates...

*pneumococcus from species of viridans group Streptococcus* S. pneumoniae = Optochin sensitive & bile soluble Viridans streptococci = Optochin resistant

(TEST): Gram-negative zoonotic infections are rarely transmitted from human to human. Which one of the following is transmitted human to human?

*pneumonia plague* / pulmonary plague - after inhalation of bacteria following intentional aerosol release or via person-to-person transmission - treatment = gentamicin or doxycyline

(TEST): The exoY gene of Pseudomonas aeruginosa can cause an increase in the production of virulence factors because it

*produces cyclic-AMP that starts a cascade leading to homoserine lactone production* ExoS - ADP-ribosylates early host proteins: ezrin, radixin, moesin proteins (ERMs) ExoT: ADP-ribosylates Crk protein --> inactivates Rac --> no wound healing ExoU: lipase activity --> quickly kills cell ExoY: Adenylate cyclase --> increased cAMP --> disrupts cells shape --> homoserine lactone production

Diseases caused by Aeromonas hydrophila

- gastroenteritis - resembles shigellosis (bloody diarrhea) - wound infections sometimes with bacteremia - systemic disease in immunocompromised patients Treatment = aminoglycosides, ciprofloxacin, trimethoprim-sulfamethoxazole

General characteristics of P. aeruginosa

- gram-negative, aerobic bacillus - gram stain = singles & pairs - can grow anerobically using enitrate or arginine - single polar flagellum mostly, but some have lopotrichous (tuft) flagella (hyperswarmers) - natural habitats = soil, vegetation, water - positive for cytochrome oxidase (unlike Enterobacteriaceae) - mucoid via abundant polysaccharide - produces pigments

Nutritional requirements of Campylobacter

- grows at *reduced O2 levels, <5% = microaerobic* - grows best at *42 C* - *unable to oxidize or ferment carbs* - *oxidase positive* = uses cytochrome c oxidase - capnophilic (require elevated CO2) - *fastidious (require special media) partilly because do not metabolize carbs either oxidatively or by fermentation* - causes inflammatory diarrhea (campylobacter jejuni) - small comma- or S-shaped, gram-negative rods - single polar flagellum (motile) - mainly causes GI diseases but also other diseases

Satellite Phenomenon

- happens on plate containing more than one organism - blood agar contains RBCs but not lysed - break open --> release heme & NAD = satellite phenomenon

Acute Q fever begins with sudden onset of

- high fevers - pneumonitis - hepatitis & hepatosplenomegaly

Defining characteristics of H. pylori

- highly motile - in gastric mucous layer/epithelial lining of stomach - oxidase positive - *urease* positive: NH3 raises pH --> protects bacteria = needed to colonize the stomach = can bind to MHC class II bearing cells & cause apoptosis - numerous virulence factors = mucinase, urease, adhesins, hemolysin, superoxide, dismutase

Diagnosis of Chlamydophila psittaci

- history of exposure to birds & clinical signs - serology (IgG/IgM), 4-fold increase in paired samples - direct immunofluorescence staining (DFA) - CF cross-reacts with C. pneumoniae, C. trachomatis - PCR (experimental) - tissue culture (research labs only) Chlamydia psittaci / Psittacosis - via inhalation of Chlamydia-laden dust from feathers or dried-out feces - atypical pneumonia / psittacosis 1-3 weeks after exposure

Epidemiology of Neisseria meningitidis

- humans = only natural hosts - spread by aerosolized secretions from respiratory tract - high incidence = 16-21 year olds - 30% of cases < 2 y/o - occurs worldwide - most common = dry, cold months of year - tends to be endemic in US - male = female - risk factors = colonization & complement deficiency

Ecology of Legionella

- in surface & drinking water - usually transmitted by aerosols - grow to high numbers between 25 & 42 C - intracellular parasite of free-living protozoa (associated with >15 species) - within amoeba

Clinical Leptospirosis

- incubation period = 5-14 days - *acute infection, septicemic stage, flu-like symptoms* - recovery when opsonizing Ig induces immune clearance - can remain in immunologically privileged sites (brain, renal tubules, eye), & re-emerge after recovery *Weil Syndrome& = severe disseminated disease, multi-organ involvement with high fever (>104 F) - vascular collapse, thrombocytopenia, hemorrhage, internal bleeding - *SPHS - Severe Pulmonary Hemorrhagic Syndrome* = common cause of death - *acute renal failure* - liver damage, jaundice - CNS involvement - myocarditis - recovery confers immunity to only infecting serovar (100's) - risks for fatal infection

Virulence of Brucella

- resists serum killing - smooth colonies are virulent - virB operon activated in phagolysosome = encodes type IV secretion system / protein secretion system --> delivers proteins into host cell --> manipulates trafficking of lysosome = able to survive where other bacteria would be destroyed

Describe rash seen in Meningitis/Neisseria meningitidis

- similar to rubella; can be seen early = transient: no longer than 48 hours, can be gone in hours - classic petechial rash = 1-2 mm; trunk, lower body; 50% at presentation; coalesce into ecchymotic lesions

Characteristics of Francisella tularensis

- small (0.2 - 0.7 uM) - poorly staining - gram-negative coccobacillus - encapsulated - obligate aerobe - no growth on ordinary culture media - cysteine-glucose blood agar (hold plates for up to 3 weeks)

Characteristics of Brucella species

- small coccobacilli - non-motile in standard conditions (mostly) - aerobes (non-fermenters) that grow slowly - virulence related to intracellular nature - penetrates skin, conjunctiva, lungs, or GI tract - penetration is followed by lymphatic spread, facultative intracellular growth in macrophages, & blood & organ invasion - *undulant fever* = peaks in evening --> slowly returns to normal by morning - elevated anti-Brucella Abs = active disease - not very common in US because cattle are immunized & milk is pasteurized

Structure of Chlamydiaceae

- small, obligate intracellular bacteria (cannot make their own ATP) - primary infect mucosal epithelial cells in eye & urogenital & respiratory tract - pass through 0.45 um filter - don't have typical cell wall (similar to gram-negatives) - cell wall active antiobiotics don't work (penicillin, cephalosporins, vancomycin) - susceptible to erythromycin & tetracycline 2 forms: - Elementary body (small, dense) = infectious; transforms into reticulate body - Reticulate body replicates in cell by fission --> reorganizes into elementary body

Phase variation of B. pertussis

- smooth virulent (phase I): hemolytic - rough colony (avirulent, phase IV): reversible mutation in virulence regulator; not hemolytic, no virulence factors - killed phase I cells used in vaccine - don't use smooth form to make vaccine = lacks virulence factors

Habitat of Acinetobacter

- soil & water - pasteurized milk - frozen foods - sink traps - ubiquitous - important in soil demineralization - can persist for long periods of time on dry or wet surfaces

Treatment for Tularemia

- streptomycin or gentamycin for 10 days - doxycycline for less ill patients

Treatment of CSD

- supportive (CSD) - erythromycin and/or doxycycline (BA or endocarditis)

Serum resistance of Meningococci

- survive in serum - can inactivate complement - block formation of C5b-9 complex (membrane attack complex) - complex deficiencies lead to increased risk of meningococcemia

Infecting Doses of Francisella tularensis

- susceptible animals infecting dose = 1 - humans infecting dose = 10 - aerosol infective dose = 50 = facultative intracellular bacterium

P. aeruginoa Lab Diagnosis

- thin gram-negative rods in singles & pairs - growth on blood (beta-hemolytic), MacConkey agar (does not use lactose), or eosin-methylene blue (EMB) agar - pigment - grape odor - combined with *rapid tests such as for oxidase activity* = sufficient - fluoresces under UV light

"Atypical" clinical course of CSD

- transient blindness - systemic: malaise, faitgue, weight loss, abdominal pain - liver & spleen lesions

Defining characteristics of Aeromonas hydrophila

- ubiquitous in aquatic environments (fresh & brackish) - oxidase-positive - facultatively anaerobic disease... - gastroenteritis - resembles shigellosis (bloody diarrhea) - wound infections sometimes with bacteremia - systemic disease in immunocompromised patients

Clinical forms of Tularemia

- ulceroglandular (75%) = entry site ulcerates & regional lymph node swollen less common or overlapping - oculoglandular - oropharyngeal - gastrointestinal - pulmonary

Diagnosis of Chlamydia trachomatis

- urinalysis > 10 WBC/high power field - gram stain of urethral secretions: >4 leukocytes/hpf - negative for intracellular diplococci (Ng) - Ct is invisible on Gram stain *PCR* (Aptima test) = 3-4 days - *Point of care* Ag detection available - Cytoplasmic inclusions seen on Giemsa or fluorescent Ab-stained smear

Mechanism of how ETEC causes infant diarrhea

1. Colonization factor antigens (CFAs) allow attachment of bacteria 2. Bacteria secrete toxins: *Heat-labile toxin LT-I & Heat-stable STa* LT toxin... - A-B toxin that acts similarly to cholera toxin - catalyzes ADP-ribosylation = increases adenylate cyclase activity = heat-labile ST toxin... - activates guanylate cyclase = hypersecretion of fluids & electrolytes = heat-stable

Mechanism of EHEC causing bloody diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome

1. Expresses Type III secretion, Tir, & intimin for binding (thus, A/E phenotype on epithelium) 2. Secreted Stx crosses epithelium by unknown mechanism & is carried by blood 3. B subunits of Stx bind to host globotriaosylceramide, GB3 4. After endocytosis of Stx, A subunit leaves compartment 5. A subunit binds to & cleaves 28S rRNA of 60S subunit --> disrupts protein synthesis 6. Endothelial cell death --> coagulation of microvasculature, platelet consumption, red cell fragmentation, decreased glomerular filtration, & renal failure - bacteria *not* internalized (shigella, salmonella are internalized) --> secrete translocated intimin receptor = initiates tighter binding --> shiga toxin secreted --> transported through host cell --> bacterolateral side --> enters endothelial layer = enters bloodstream

Mechanism of how EPEC causes infant diarrhea

1. Loose attachment: bundle-forming pili (Bfp) 2. Type III secretion of translocated intimin receptor (Tir) 3. Localization of Tir to host membrane 4. Binding of intimin to Tir 5. Effacement of microvilli 6. Loss of effective absorption by microvilli

Mechanism of *Heat-stable toxin STa* of ETEC

1. Small monomeric toxin is secreted & binds to host guanylyl cyclase 2. Activated guanylyl cyclase catalyzes GTP to cGMP --> stimulates secretion of chloride = watery diarrhea - CFTR = cystic fibrosis transmembrane conductance regulator, a gated channel for chloride secretion

Mechanism of *Heat-labile toxin LT-I* of ETEC

1. Toxin is endocytosed 2. Subunit leaves compartment & transfers ADP-ribose from NAD to GDP subunit of Gs 3. Phosphorylated Gs regulates adenylyl cyclase, which causes increase in intracellular cAMP 4. Chloride secretion increases & sodium absorption decreases, resulting in water diarrhea LT-I is similar to cholera toxin = one A subunit & 5 B subunits = classic AB toxin

(TEST): One of the indicators of a urinary tract infection in an individual is the presence of the following minimum number of bacterial colony-forming units (CFU) per milliliter of urine.

100,000

Urinary tract infections are identified not only by isolation of the pathogenic bacteria but quantification present in a mid-stream clean-catch urine sample; proof of infection is attained by bacterial numbers above

100,000 bacteria/ml

Colonization of CF patients

1st colonized by S. aureus --> then Pseudomonas

In P. aeruginosa, this is an autoinducer molecule produced during quorum sensing.

3-oxo-C12-HSL (PAI-1) = homoserine lactone (HSL) - available to bind LasR via production from nearby bacteria

Empiric treatment for Neisseria meningitidis

3rd generation cephalosporin - need one that can penetrate blood-brain barrier = *ceftriaxone* - prophylaxis for close contacts = *rifampin*

Only stage of Trichomonas vaginalis (pathogen)

4 anterior flagella undulating membrane single nucleus axostyle - attach to cervica/vaginal or prostatic/urethral epithelium - acquired by sexual intercourse (STD)

HPV increases cancer risk...

90% anal 65% vaginal 60% oropharyngeal 50% vulvar 35% penile cancers

"Typical" clinical course of Cat Scratch Disease (CSD)

= 7-12 days after scratch = red-brown skin papule - gradual regional lymph node enlargement - runs predictable self-limited course - nodes remains enlarged 2-3 months = painful & tender = may suppurate

Mucocutaneous eruptions caused by M. pneumonia

= maculopapular, vesicular, or erythematous eruptions - *skin rashes* - often extremities - *ulcerations* of both oral & vaginal mucosa - *Stevens-Johnson syndrome* = oral ulceration with sin rash & conjunctivities (*erythema multiforme*)

Causes diarrhea in children and adults in both developing and developed countries. Chronic diarrhea in children in developing countries associated with growth retardation. Auto-agglutinate into "stacked-brick" arrangement mediated by bundle-forming fimbriae (aggregative adherence fimbriae I & II).

EAEC - stimulates mucus secretion --> traps bacteria in biofilm on epithelium of small intestine - microvilli become shortened - mononuclear cells infiltrate - hemorrhage can occur

(TEST): This common sexually transmitted disease agent can ascend the peripheral sensory nerves to reach the dorsal root ganglia where it can remain latent and later re-emerge to cause recurrent outbreaks of disease.

Herpes simplex virus

Associated Disease: Chlamydia trachomatis serotypes L-1, L-2, L-3

LGV - *Lymphogranuloma venereum* - painless initial lesion, inguinal bubos, draining fistulas, proctitis, genital elephantiasis

Family of HIV

Lentivirus (Retroviridae)

Coiled, Gram-, aerobic, motile, hooked ends, paired axial flagella, able to burrow in to tissue. 50% in Hawaii. Transmission via contact with water (swimming), food, or soil containing rodent *urine*.

Leptospira interrogans or biflexa - occupation (animal contact) = risk factor - urine of cattle, pigs, horses, dogs, & wild animals - transmission via contact with animals - transmission via contact with animal blood - person to person transmission rare

Vector of HGE - E. ewingii

Lone Star tick - reservoirs = chipmunk, vole, canines

Epidemic Typhus caused by

Louse born - R. prowazekii - human to human transmission via lice in crowded unsanitary conditions - high fever, intense headache, macular skin rash, diffuse vasculitis

Bullseye rash present in 70% of patients who have

Lyme Disease - arthritis prominent - Bells palsy - reticuloneuropathy - predominately in Northeast & upper Midwestern states

Disease caused by Borrelia burgdorferi

Lyme Disease - vector = tick - reservoir = deer, ticks = febrile illness, erythema migrans (bulls-eye rash), arthritis, facial palsy, carditis - diagnosis via serology, culture - treatment = *doxycycline*, amox, cefu, *ceft/cefo*

Mycoplasma species: Non-gonococcal urethritis.

M. genitalium

Mycoplasma species: Pyelonephritis, salpingitis, cervicitis, vaginitis, prostatitis. Post-partum fever, peripartum sepsis. Neonatal conjunctivitis. Surgical wound infections.

M. hominis

Allows Klebsiella to become resistant to broad range of beta-lactams (such as carbapenem). First detected in Klebsiella pneumoniae isolated from patient in 2008. Has spread to other bacteria, e.g., E. coli, Acinetobacter, Enterobacter

NDM-1: metallo-beta-lactamase-1 ("New Delhi Metallo-beta-lactamase")

Leading cause of burn infections

P. aeruginosa

B. pertussis Virulence Factors

Pertussis toxin (part of some vaccines) - leukocytosis - disable phagocytic cells Adenylate cyclase toxin - disable phagocytic cells Dermonecrotic toxin - cytopathic, tissue damage Filamentous hemagglutinin Fimbriae Pertactin - outer membrane protein LOS + Tracheal cytotoxin (TCT) - loss of ciliate cells - killing of phagocytic cells Trachael cytotoxin + endotoxin (LOS) --> IL1 + nitric oxide --> Inflammation; extrusion of ciliated cells

Pseudomonas Adhesins

Pili = type IV = long & filamentous = twitching motility = adhere to epithelial cell of upper respiratory tract (& other epithelial cells) = binds to galactose, mannose, sialic acid receptors such as asialo-GM1 - bacterial proteases can cleave host fibronectin --> exposes more binding sites for pili - opportunistic ahderencce in people with influenze or other underlying conditions that compromise epithelial cells Surface lectin LecA Alginate Flagellum

Swimmers & Swarmers.

Proteus - swimmers = 8-10 flagella - swarmers = peritrichous flagella

44% of MDRAB from

Pseudomonas - 34% from Salmonella - 18% from E. coli - 4% from other bacteria

Enteric Non-fastidious Organisms that are non-fermenting & oxidase-positive

Pseudomonas aeruginosa - absolutely requires oxygen - requires oxygen for utilization of glucose (oxidation) - *have* cytochrome C oxidase

(TEST): Leading cause of nosocomial pneumonia

Pseudomonas aeruginosa - leading cause of burn infections - leading cause of contact lens-associated corneal infections

Pigments produced by Pseudomonas aeruginoa

Pyoverdin = yellow-green Pyocyanin = blue-green Pyorubin = red-brown

Disease cause by Coxiella burnetii

Q fever - vector = ticks (humans via inhalation) - reservoir = cattle, sheep, goats, cats - acute: high fever, pneumonitis - chronic = endocarditis - diagnosis = serology, PCR - treatment = *doxy*, (TMP/SMX), *doxy + hydrochlor*

Proteus treatment: uncomplicated patients

Sulfa-trimethoprim or Ciprofloxacin if patients.. - has been on short-term catheterization - has not been critically ill - believed not to have polymicrobial infection

Plague cycles

Sylvatic cycle - transmission among wild rodents by fleas - prairie dogs = important US reservoir; ground squirrels Urban cycle - transmission among urban rats with rat flea as vector

Causative agent of Venereal Syphilis (STD)

T. pallidus pallidum

Result of Lac- on TSI

TBS = alkaline medium used to grow Vibrio cholerae - *when bacteria are growing on a sugar, they produce acid pH = yellow* - when bacteria are growing on peptones, their pH is closer to neutral = red - reduces thiosulfate to H2S that reacts with Fe to produce FeS

Genital ulcers present in Chancroid

Tender, erythematous papules ulcers. *Painful*, purulent, irregular shape, soft undermined edges, *often multiple*. Exudate. - lymphadenopathy: tender, regional, painful, erythematous, supperative nodes, *usually unilateral* - Haemophilus dycreyi

Result of plating E. coli on *TSI / Triple Sugar Iron Agar Slant*

can use other sugars = happily grows --> stays yellow after 48 hours-ish - Enterobacteriaceae prefer glucose first - produce acid = yellow agar (first 12 hours) oxygen bubble production (shigella, salmonella don't) - shigella & salmonella cannot use lactose & sucrose = go for peptides --> indicator change in agar (after 12 hours) --> slant turns red from alkaline conditions

Most common form of Bartonella in USA

cat scratch disease

(TEST): Selective and differential media for identifying gram-negative bacilli contain different carbon sources for growth, and bacterial carbon metabolism is controlled by operons which turn on or turn off depending upon the levels of cyclic AMP produced. This mechanism of metabolic control is best defined as

catabolite repression

B. abortus associated with what animals?

cattle

Treatment for Aeromonas hydrophila

chronic diarrheal disease or systemic infection - *ciprofloxacin* - *aminoglycosides & trimethoprim-sulfamethoxazole* = also active - resistant to beta-lactam antibiotics & erythromycin

Most gram-negative rods that cause UTIs originate in the

colon - contaminate the urethra - ascend into the bladder - may migrate to the kidney or prostate

(TEST): To cause infection, Neisseria meningitidis must

colonize the human nasopharynx

Strains of P. aeruginosa adapted to CF lung have mutations that cause hyperinflammatory response...

lasR = transcriptional activators triggered by environmental cues = codes for transcription factor LasR - triggers LasI --> begins autoinduction loop within bacterial cell by producing more PAI-1 -->more PAI-1 can bind & activate LasR (autoinduction loop) = can also singal neighboring bacteria

What characteristic makes it easy to catch Treponema pallidum - Syphilis

low infectious dosease: ID50 = 57 spirochetes

Know how cellular membrane protrusions induced by N. meningitidis leads to bacteria engulfment within host cells

membrane ruffling: pili + epithelial cell membrane --> actin activation within epithelial cells --> invagination --> membrane surrounds Neisseria cell = enters epithelial cell

Coxiella burnetii of Q fever infects...

monocytes/macrophages = rod-shaped spore-like forms & larger cell variants

Mycoplasma & Ureaplasma usually associated with what environments?

mucosal surfaces - diseases of respiratory & urogenital mucosa

(TEST): The binding to mammalian cells by Pseudomonas aeruginosa via pili or flagella is augmented by

neuraminidase

Genital ulcers of Donovanosis

small, *painless pustules*, ulcers shallow, erythematous, sharply demarcated, may expand, deepen, become necrotic, can be dry or nodular Granuloma inguinale via Klebsiella granulomatis - ulcerative genital lesions - endemic in less developed lesions

Genital ulcers present in LGV

small, painless vesicle/papule, *usually single*, heals rapidly, often not noticed - lymphadenopathy = painful, matted, firm, large nodes supperate with fistula tracts, *usually unilateral* Lymphogranuloma venereum - caused by Chlaymydia trachomatis serotypes L1, L2, & L3 - small, painless, ulcers on genitals --> swollen, painful inguinal lymph nodes that ulcerate (buboes) - treat with doxycycline

Progression of rash in RMSF

starts at extremities --> inward toward trunk = centripetal spread = center seeking

Proteus treatment: individuals undergoing long-term catheterization or suffering from polymicrobial infections & who are noncritical

sulfa-trimethoprim or second-generation cephalosporin

(TEST): Proteus species are typically resistant to

tetracyclines - nitrofurantoin (commonly given for UTIs) is not effective for Proteus - Tigecycline alone is not effective for Proteus (must be combined with amikacin)

(TEST): Infections caused by Pseudomonas aeruginosa are particularly worrisome because

the organism is frequently resistant to multiple classes of antibiotics

Serology of H. influenza

types a-f with type b being the most important (Hib) nontypeable (NTHi) - no capsule - nontypable goes in between cells --> basement membrane --> lamina propria --> grows --> can go to bloodstream

*SAFE Strategy* for Chlamydia trachomatis

Developed by WHO Community-based, integrated plan of action that includes both prevention & treatment strategies. - *S*urgery = simple, 15 minute procedure done in village setting - *A*ntibiotics - treat active infection = tetracycline ointment, oral azithromycin, doxycycline, erythromycin - *F*ace washing - removes discharge = can increase transmission of disease - *E*nvironmental change - increases access to clean water & better sanitation

In RMSF, damage to blood vessels in RMSF can lead to impaired circulation & necrosis, especially in extremities, requiring amputation.

Digital necrosis

(TEST): Treatment for HGE/HGA (human granulocytic ehrlichiosis/anaplasmosis)

Doxycycline

Treatment for Chlamydophila psittaci

Doxycycline (Tetracycline) Erythromycin

Most common gram-negative rod isolated from sepsis

E. coli - more than 80% of community-acquired UTIs (usually from fecal area) - large cause of gastroenteritis in developing countries

Enteric Non-Fastidious Organisms that ferment glucose & are oxidase-negative

E. coli Klebsiella pneumonia Proteus mirabilis - lack cytochrome c oxidase but still utilize O2

(TEST) Primary virulence mechanism of Salmonella species that cause gastroenteritis

Invasion of M cells of Peyer's patches

Pseudomonas - TSI - Urea - Indole

*- Alkaline over no change* *- Negative* *- Negative* Requires oxygen but not metabolizing glucose - takes available amino acids & turns them into carbon source & energy source

Treatment of Klebsiella

*3rd generation cephalosporin plus gentamicin, ciprofloxacin, tetracyclin, erythromycin, sulfa-trimethoprim* - relapses with antibiotics can occur

(TEST): A 47-year-old male who works on a timber farm had two courses of antibiotic treatment for right lower lobe pneumonia. He felt better but developed an ulcerative lesion on his left forearm. A center punch biopsy revealed numerous granulomatous cells but no microorganisms were seen microscopically. A second biopsy from the periphery of the lesion was performed. Which of the following would likely describe the microorganisms seen?

*A broad budding yeast* Blastomycoes dermatitidis - isolated from soil & rotten wood - rarest systemic fungal infection - hardest to get; hardest to have!

(TEST): A 47-year-old male who works on a timber farm had two courses of antibiotic treatment for right lower lobe pneumonia. His pneumonia resolved, but he subsequently developed an ulcerative lesion on his left forearm. A center punch biopsy revealed numerous granulomatous cells, but no microorganisms were seen microscopically. A second biopsy from the periphery of the lesion was performed. Which of the following would likely describe the microorganisms seen in the second biopsy?

*A broad-based budding yeast* Blastomyces dermatitidis - fungi isolated from soil & rotten wood - rarest systemic fungal infection - hardest to get & hardest to have!

(TEST): A 45-year-old male has a history of smoking two packs of cigarettes a day. He works for an open-water pond servicing company. He presents with complaints of shortness of breath and flu-like symptoms that have been present for about a week. Cultures of lung sputum fail to grow anything on blood agar. Based on this history, which one of the following laboratory tests would likely be the most informative?

*A urine antigen test (Lp1 specific)* Legionella pneumophila - gram negative rod - gram stains poorly = use *silver* stain - grow on *charcoal* yeast extract - hyponatremia - aerosol transmission via env'tal water source habitat *Legionnaire's disease* - severe pneumonia (often unilateral & lobar), fever, GI, & CNS symptoms - common in *smokers* & in chronic lung disease

(TEST): Contact lens users are at risk for corneal infection characterized by keratitis with a ring infiltrate, by

*Acanthamoeba species* - chronic, granulomatous, brain infection in immunocompromised patients (AIDS) - treatment = multiple antifungal drugs with pentamide - may infect cornea (in immunocompetent ppl), often when contact lenses are not properly cleaned

(TEST): Contact lens users are at risk for corneal infection characterized by keratitis with a ring infiltrate by which of the following organisms?

*Acanthamoeba species* = free living amoeba - GAE, granulomatous amebic encephalitis, keratitis - enters eye --> can cause severe keratitis in otherwise healthy individuals, particularly contact lens users - trophozoites & cysts with wrinkled-walls - amoeba have "bull's-eye" nuclei

Protozoan that is free living & is such that acquisition does not generally indicated fecal contamination

*Acanthamoeba* - free-living organism with sturdy cyst stage that is found in dust - acquired via homemade saline solutions for soft contact lenses - chronic, granulomatous brain infection in immunocompromised patients - treatment = multiple antifungal drugs with pentamidine

(TEST): The state Department of Health was recently called in to investigate an outbreak of bacterial infections in a regional hospital. The initial infection appeared to occur in an intensive care unit and quickly spread throughout the hospital. Which one of the following was likely identified as the cause?

*Acinetobacter baumannii* - lungs protected form this by *neutrophils* - resistance islands acquired via *horizontally* from other organisms - key source of infection in debilitated patients in hospital - problematic for neutrophilic febrile patients

Gram-negative rods of the Moraxellaceae family. Non-motile & non-fermentative. Encapsulated & nutritionally versatile. Often confused with Neisseria & Morexella. Most frequent clinical isolate.

*Acinetobacter baumannii* - lungs protected from this by *neutrophils* - resistance islands acquired *horizontally* from other organisms - ventilator-associated neumonia via *increased antibiotic resistance* - grows on *MacConkey Agar* & is *oxidase-negative* - ability to perisist in hospitals via *ability to from biofilms* - type IV pili - differentiated from other Moraxellaceae by oxidase test = only members of Moraxellaceae to lack cytochrome c oxidases - high rate of antibiotic resistance - referred to as Iraqibacter - AbaR resistance islands

(TEST): The state Department of Health was recently called in to investigate an outbreak of bacterial infections in a regional hospital. The initial infection appeared to occur in an intensive care unit and quickly spread throughout the hospital. Which one of the following was identified as the likely cause?

*Acinetobacter baumannii* - most infections typically occur in ICUS - increased occurrence with increased stay - opportunistic infection

A recent immigrant from rural Brazil presents with a swollen face & extremely poor dental hygiene, including moss of an adult tooth, which appears to be the focus of the current infection. There are two open ulcers on the outside of the swollen cheek. Small yellow "grains" are seen in one of the ulcers. Gram stain shows purple-staining fine filaments. What is the most likely disease?

*Actinomycotic mycetoma* = lumpy jaw = form of mycetoma - caused by Actinomyces part of gingival crevices flora Mycetoma - localized, chronic, noncontagious infection involving cutaneous & subcutaneous tissues - sometimes used to describe infections due to *Actinomycetes*, Nocardia species - Disease due to filamentous fungi = eumycetoma

Exopolysaccharide produced by P. aeruginosa in certain conditions. Responsible for mucoid phenotype. Enhances bacterial adhesion. Protects bacteria from attack.

*Alginate* - transcription = binding of bacteria to surface = important in biofilm formation - bacterial alginate lyase cleaves alginate --> releases bacteria from biofilm - nonmotile when touch surface

(TEST): Antiobiotic that is bactericidal for Escherichia coli under the right conditions

*Amikacin* = *most bactericidal of protein synthesis inhibitors* - used in treatment of serious gram-negative infections, especially those resistant to gentamicin or tobramycin - bactericidal - irreversible inhibition of initiation complex via binding of 30S subunit - can cause misreading of mRNA - also block translocation - required oxygen for uptake - ineffective against anaerobes synergistic with beta-lactam antibiotics

Tigecycline alone is not effective for Proteus but can be when combined with

*Amikacin* Proteus... - water organisms - display swarming motility - do not ferment lactose - produce urease & H2S - cause UTIs & infections in immunocompromised patients

(TEST): This inhibitor of bacterial protein synthesis is the most bactericidal of the protein synthesis inhibitors, is not effective for strict anaerobes.

*Amikacin* - for severe gram-negative infections, especially those resistant to gentamicin or tobramycin

Polyene antigunfal agent used for many life-threatening fungal infections

*Amphotericin B* - binds to ergosterol, a major component of fungal cell membranes - form amphotericin pores --> alters membrane stability - broadest spectrum of activity - initial treatment for severe systemic fungal infections: Candida albicans, Histoplasma capsulatum, Cryptococcus neoformans, Coccidiodes immitus, Blastomyces dermatitidis, Aspergillus species, Sporothrix schenckii

(TEST): A 27-year-old female presents to the emergency room with complaints of left flank pain, fevers and chills. She noted increased urinary frequency and foul-smelling urine on the day prior to admission. She presented with a temperature of 39.8º C and physical examination showed left costovertebral angle tenderness. Urinalysis of a clean-catch urine sample was notable for >40 white blood cells, 4 to 10 red blood cells and 4+ bacteria per highpower field. Urine culture was positive for >100,000 CFU of a lactose-positive gram-negative rod. Urine culture suggests etiological agent could be Escherichia coli, Klebsiella, or Enterobacter. The antibiotic therapy of choice for this patient would include

*Ampicillin* - useful for infections caused by Haemophilus influenza, Streptococcus pneumonia, Streptococcus pyrogenes, Neisseria meningitidis, Proteus mirabilis, Enterococcus faecalis E. coli treatment - treatment for UTIs = cephalosporins, sulfa-trimethoprim/sulfamethoxazole, sometimes nalidixic acid, tetracycline

(TEST): Human infection with what parasite results from penetration of skin with infectious filfariform larvae?

*Ancylostoma duodenale, Strongyloides stercoralis, Necator americanus* Ancylostoma duodenale, Necator americanus (hookworms) - intestinal infection causing anemia by sucking blood from intestinal wall - larvae penetrate skin - treatment = bendazoles or pyrantel pamoate Strongyloides stercoralis (threadworm) - intestinal infection causing vomiting, diarrhea, epigastric pain - larvae in soil penetrate skin - treatment = ivermectin or bendazoles

(TEST): Which of the following statements about Bordetella pertussis infection is CORRECT?

*Antibiotics must be given before the end of the catarrhal stage in order to be useful* - treatment primarily supportive - erythromycin in prodromal or catarrhal stage may prevent disease - later therapy during paroxysmal stage does not alter the cours of illness but may decrease bacterial shedding

(TEST): This organism, usually acquired in Northeastern and Upper Midwestern states, infects red blood cells and causes a hemolytic-like disease that may be fulminant in splenectomized individuals, and is characterized by fever, hemolytic anemia, muscle aches and pain, and sometimes hepatomegaly.

*Babesia microti* = Babesiosis - infection like malaria - transmitted by bite of tick - causes fever & hemolysis (anemia) - treatment = quinine & clindamycin - giemsa or wright-stained thin & thick blood smear = ring-shaped trophozoites - distinctive cross or x-shaped tetrade of merozoites (Maltese cross)

A 33-year-old woman develops painful, swollen right knee with limited range of motion due to pain. Physical exam shows that he right knee is erythematous and warm to touch. Culture of the joint fluid aspirate grows organisms on chocolate agar but not on blood agar. The most likely causal organism has what property?

*Antigenetically variable pili* - septic arthritis caused by direct invasion of joint space by microorganism - infected joints = triad of symptoms = low-grade fever, pain, impaired range of motion that develops over few days - weeks Causal organism = *Neisseria gonorrhoeae* = sexually transmitted gram-negative, oxidase positive diplococcus - cultured on chocolate agar but not on blood agar - variant of chocolate agar = Thayer-Martin agar - *may express over 1 million variants of pili = virtual absence of immunity to reinfection with this agent* = *most common cause of septic arthritis in otherwise healthy, sexually active adults* - treatment = ceftriaxone

(TEST): Is this ok? A cancer patient developed a spiking fever and difficulty breathing four days after surgery to remove a lung tumor. The incision showed fresh signs of inflammation, with a distinctive sweet odor emanating from the wound. Blood cultures were started, and a swab of the wound was also cultured. The patient was in critical condition and a decision was made to treat the infection with ertapenem plus tobramycin.

*Appropriate & sufficient antibiotic therapy*

(TEST): Loeffler's Syndrome, a pneumonitis plus peripheral eosinophilia due to larval forms migrating thru the lung, is observed during human infection for each member of this group.

*Ascaris lumbricoides, Necator americanus, Strongyoides stercoralis* Intestinal Nematodes / Roundworms - larval form that migrates through tissue & into lung at some stage of their life cycle --> larvae grow in lung = coughed up & swallowed into intestine --> grow into adult worms

Grows as a mold in the human host

*Aspergillus fumigatus* - grows as a *mold* - not dimorphic - septate hyphae; V-branching - radiating conidia (infectious particle) diseases - allergic bronchopulmonary aspergillosis (HS), fungus balls, cornea, etc

(TEST): A patient previously treated for tuberculosis presents with a necrotic lung infection. Biopsy specimens reveal an organism with V-branching, non-septate hyphae. Microscopic exam of a culture of the organism revealed conidiophores with an array of conidia. The most likely infecting organism is

*Aspergillus fumigatus* - grows only as *mold*; not dimorphic - septate hyphase - V-branching - radiating conidia (infectious particle)

(TEST): Grows as mold in human host

*Aspergillus fumigatus* - septate hyphae branch at 45 degrees Acute Angle - produces conidia in radiating chains at end of conidiophore - can cause aspergillomas in pre-existing lung cavities, especially after TB infection - Allergic bronchopulmonary aspergillosis (ABPA): HS response associated with asthma & cystic fibrosis

A severely neutropenic patient presents with pneumonia. Bronchial alveolar fluid shows dichotomously branching (generally with acute angles), septate hyphae. What is the most likely causative agent?

*Aspergillus* - spores are commonly airborne - controlled by phagocytic cells - in severe neutropenia, risk of infection is high Aspergillus fumigatus - septate hyphae branch at 45 Acute Angle - produces conidia in radiating chains at end of conidiophore - some species produce aflatoxins = HCC association

Treatment for Chlamydia trachomatis - Perinatal (Inclusion) Conjunctivitis (Serotypes D- K)

*Azithromycin or Doxycycline* - topical treatment is ineffective - oral azithromycin = first line therapy *acute, purulent, red eyes, swollen eyelids* Chlamydia trachomatis --> infects eyes & genitals - trachoma = chronic conjunctivitis = leading cause of *preventable blindness* - disease of poverty - US: Native Americans = group most frequently infected - children = main reservoir - transmission via hand-to-hand transfer of infected eye secretions & by sharing contaminated clothing or towels - blindness develops slowly over 10-15 years

(TEST): Treatment for community-acquired pneumonia due to Mycoplasma

*Azithromycin* - campylobacter jejuni - gonorrhea - chancroid - binds bacterial 50S - bacteriostatic

Treatment for Chlamydia trachomatis

*Azithromycin* or doxycycline (alternative, erythromycin) Azithromycin or Amoxicillin in pregnancy

Treatment of Granuloma inguinale - Donovanosis

*Azithromycin*, Doxycyline, Erythromycin, Tetracycine, TMP/SMX

Bordetella related to contact with infected *animals*

*B. bronchiseptica* - small, gram-negative, rod-shaped - causes infectious bronchitis in dogs & other animals but rarely infects humans

Burkholderia that causes pulmonary infections, like for BCC

*B. gladioli* - aerobic gram-negative rod-shaped bacteria - causes disease in both humans & plants - can live in symbiosis with plants & fungi

Burkholderia in alcoholic, diabetics, people with chronic renal or lung disease. Melioidosis infections. Infection by cutaneous route. Pulmonary infection. Without appropriate antimicrobial therapy, progresses to overwhelming sepsis & death.

*B. pseudomallei* - gram-negative, bipolar, aerobic, motile rod-shaped - soil-dwelling - endemic in tropical areas - flagella - produce exo- & endotoxins

(TEST): This organism, usually acquired in Northeastern and Upper Midwestern states, infects red blood cells and causes a hemolytic-like disease that may be fulminant in splenectomized individuals, and is characterized by fever, hemolytic anemia, muscle aches and pain, and sometimes hepatomegaly.

*Babesia microti* = Babesiosis - fever & hemolytic anemia - predominately in *northeastern United States, upper mid-west* - asplenia increases risk of severe disease - transmission = Ixodes tick (same as Borrelia burgdoreferi of Lyme disease; may coinfect humans) = *nymph stage* - Blood smear: ring form, "Maltese cross"; PCR - treatment = *Atovaquone + azithromycin* or *Clindamycin + quinine* - mostly older people

2 biotypes of V. cholerae O1

*classical* - caused each of the first 6 documented pandemics *el tor* - caused the 7th (1960s - 1970s)

A logger undergoing chemotherapy for cancer has developed pneumonia & skin lesions. Biopsy of the skin lesions demonstrates the presence of large yeasts with thick cell walls & broad based buds. What is the most likely causative agent?

*Blastomyces dermatitidis* - fungi isolated from soil & rotten wood - rarest systemic fungal infection - infection? = rarely asymptomatic or mild - chronic disseminated disease with weight loss, night sweats, lung involvement, skin ulcers - hardest to get & hardest to have! - has double refractory wall & buds with broad base of attachment to mother cell - Eastern United States & Central America - causes inflammatory lung disease & can disseminate to skin & bone - form granulomatous nodules

(TEST): A 37-year-old African-American male with no significant past medical history, and social history significant for smoking and intermittent incarceration, had two courses of antibiotic treatment for left lower lobe pneumonia. Approximately one month later, the patient presented back to the emergency department with persistent fever, malaise and a painful right arm mass, which had been present for two weeks. He denied any trauma to the arm. A biopsy revealed a broad-based large budding yeast. About four months previously he had gone on several hunting trips in north Mississippi. The likely diagnosis is

*Blastomycosis* - histoplasma & blastomyces are endemic to vast areas that drain into MS River - Eastern United States & Central America - causes inflammatory lung disease & can disseminate to skin & bone - forms granulomatous nodules - broad-base budding (same size as RBC)

(TEST): Agent of facultative myiasis

*Blow fly larvae* Myiasis - parasitic infection of body of live mammal by fly larvae/maggots that grow inside host while feeding on its tissue - can create infestation even on unbroken skin

(TEST): Epidemic relapsing fever (Borrelia recurrentis) and epidemic typhus (Rickettsia prowazekii) are transmitted by this arthropod vector.

*Body lice* Borrelia recurrentis / Relapsing fever - only Borrelia transmitted to humans via body louse (Pediculus humanus) Rickettsia prowazekii / Epidemic typhus - lice or fleas from infected squirrels bite humans - spares palms, soles, & face - invade endothelial cells of blood vessels

(TEST): Many bacterial pathogens are readily transmitted from human to human. What is likely to be transmitted by this route?

*Bordetella pertussis* / Whooping Cough - highly contagious diease with transmission occurring via respiratory secretions on hands or in aerosolized form - week-long incubation period is followed by 3 stages of disease: catarrhal stage, paroysmal stage, convalescent stage

(TEST): The most likely cause of a tick-borne febrile illness characterized by an expanding erythema migrans (bull's-eye rash), arthritis and facial palsies is

*Borrelia burgdorferi (Lyme disease)*

Chronic infection with this organism is characterized by recurring arthritis, neurological disorders, and poor response to antibiotics.

*Borrelia burgdorferi* Early disseminated stage (stage 2) - neurologic - brief attacks of arthhritis of large joints (knee) Late stage (stage 3) - chronic arthritis - encephalopathy

A 47-year-old male who works on a timber farm had two courses of antibiotic treatment for right lower lobe pneumonia. He felt better but developed an ulcerative lesion on his left forearm. A center punch biopsy revealed numerous granulomatous cells but no microorganisms were seen microscopically. A second biopsy from the periphery of the lesion was performed. Which of the following would likely describe the microorganisms seen?

*Broad budding yeast* Blastomycoses - tiber. punch biopsy = granulomatous cells. - eastern united states & central america - causes inflammatory lung diseases & can disseminate to skin & bone. - environmental assocaiation

(TEST): Bite of this arthropod causes a localized necrosis at the bite site

*Brown Recluse spider*

(TEST): A group of migrant farm workers present with symptoms of aches, chills, fever, and drenching sweating episodes. The workers often prepare and share meals together, using food from the farms on which they work, including raw and natural products. Which one of the following is a likely cause of their infection?

*Brucella melitensis* (goats) - human acquire Brucella via direct contact with infected animal meat or aborted placentas, or *ingestion of infected milk products* - symptoms = systemic with *fever, chills, sweats,* loss of appetite, *backache, headache,* sometimes lymphadenopathy - patients = workers in meat-packing industry (beef), veterinarian, *farmer*, or a traveler who consumes dairy (cow or goat) products in Mexico or elsewhere

(TEST): A 28-year-old female presents with spiking fever, sweating, weakness, headaches, muscular pain, and body aches. Approximately two weeks earlier she drank some unpasteurized goat milk. Which of the following is the likely cause of her illness?

*Brucella melitensis* (goats) - humans acquire Brucella via direct contact with infected animal meat or aborted placentas, or ingestion of infected milk products - neither buboes nor a primary skin ulcer appear - undulant fever - rarely fatal - culture of organism from blood, bone marrow, liver, or lymph nodes

Black Death...

*Bubonic Plague* - endotoxin-related symptoms - disseminated intravascular coagulation (DIC) - cutaneous hemorrhage

Campylobacter with propensity to spread to bloodstream

*C. fetus* - septicemia, GI disease, meningitis, spontaneous abortion - gram-negative, motile bacteria - characteristic "S"-shaped rod morphology similar to members of genus Vibrio - oxidase-positive

Citrobacter: splenic abscess, neonatal meningitis

*C. freundii* - facultative anaerobic gram-negative bacteria - Enterobacteriaceae family - long bacterial rods - soil organism but also found in water, sewage, food, & intestinal tracts of animals & humans - plays important role in nitrogen cycle in environment - reduces nitrate to nitrite in environment

Citrobacter: causes sepsis, meningitis, and brain abscesses in neonates.

*C. koseri* - gram-negative, nonspore-forming bacillus - slow lactose fermentation (alone with serratia) - facultative anaerobe - motile via peritrichous flagella - member of fam of Enterobacteriaceae - part of normal flora of human & animal digestive tracts - may acts as opportunistic pathogen

Recognize Proteus on Blood Agar & MacConkey Agar

- follows nutrient gradient - hunter/gatherer - no lactose fermentation - oxidase negative - H2S production on TSI agar (as well as salmonella)

A 29-year-old man comes to the physician because of a 3-week history of swollen & painful knees & toes. He also has some low back stiffness that is worse in the morning & he has been treated recently for conjunctivitis. Five weeks ago, he had episodes of myalgia, crampy abdominal pain & frequent loose bowel movements with occasional blood, which lasted a few days & resolved on its own. He subsequently developed urgency, clear urethral discharge, & dysuria. He is sexually active & has a mnoogamous relationship with the same person for the past 2 years. His temperature is 37.2 C (99 F), pulse is 76/min, respirations are 12/min, & BP is 128/74 mmHg. Gram stain reveals absence of any bacteria in penile discharge. What infection is likely to be found in this patient's history?

*Campylobacter jejuni infection* = *reactive arthritis* (Reiter syndrome) - acute onset of arthritis (usually asymmetric & additive) - involvement of new joints over priod of few days to 2 weeks - may also have history of diarrhea 1-2 weeks prior - joints of lower extremities most commonly involved, but wrists & fingers can be affected - dactylitis (sausage digit) = diffuse swelling of solitary finger or toe = distinctive feature of reactive arthritis & psoriatic arthritis - tendinitis & fasciitis are common - spinal pain & low back pain - conjunctivitis, urethritis (dysuria, urgency, urethral discharge), diarrhea, skin lesions Reiter = *can't see, can't pee, can't climb a tree* - 75% of patients = HLE-B27-positive - most patients = younger males - Guillain-Barre syndrome & Hemolytic-uremic syndrome = other complications

Is resistant to complement- and antibody-mediated lysis (S protein of capsule prevents killing).

*Campylobacter* - gram-negative, comma or S shaped (with polar flagella), oxidase positive - grows at 42 C - major cause of bloody diarrhea, especially in children - fecal-oral transmission via person-to-person contact or via ingestion of undercooked contaminated poultry or meat, unpasteurized milk - contact with infected animals - common antecedent to Guillain-Barre syndrome & reactive arthritis

(TEST): Which one of the following causes the widest range and greatest variety of clinical presentations of fungal infections in humans?

*Candida albicans* - diagnosed with KOH prep of skin scrapings or with stains & cultures of biopsies tissue or blood - blood test for beta-D-glucan, component of fungal cell wals - systemic infection via IV therapy with amphotericin B, fluconazoke, or echinocandin (caspofungin or micafungin)

(TEST): A female seeks evaluation for a vaginal discharge. Pelvic exam reveal an odorless, thick, white discharge adherent to the vaginal walls, vaginal erythema but no cervical discharge. KOH prep of the discharge reveals pseudohyphae. The most likely diagnosis is

*Candida vaginitis* / vulvovaginitis - inflammation - thick, white, "cottage cheese" discharge - pseudohyphae - pH normal (4 - 4.5) - treatment = -azoles

A premature baby, now 4 days old, has developed a white coating on her buccal mucosa extending onto her lips. It appears to be painful. What is the most likely causative agent?

*Candida* = thrush - dimorphic - forms pseudohyphae & budding yeasts at 20 C - germ tubes at 37 C - treatment = nystatin, fluconazole, or caspofungin for oral/esophageal

A patient has a dry, scaly, erythematous penis. Skin scales stained with calcofluor white show fluorescent blue-white yeasts & few pseudohyphae. What is the causative agent of this dermatophytic look-alike?

*Candida* balanitis - may cause skin infections that resemble some dermatophytic infections

(TEST): The antigen assay for the diagnosis of a specific opportunistic fungal disease is designed to detect which of the following in a patient sample of urine, blood, or cerebral spinal fluid?

*Capsular polysaccharide*

(TEST): The antigen assay for the diagnosis of cryptococcosis is designed to detect which of the following in a patient sample of urine, blood, or cerebral spinal fluid?

*Capsular polysaccharide* Cryptococcus neoformans = polysaccharide encapsulated yeast (not dimorphic) - meningoencephalitis - key to diagnosis = lumbar puncture --> analyze CSF --> India ink stain = yeast cells with surrounding halo, polysaccharide capsule - more sensitive test = cryptococcal antigen test = detects cryptococcal polysaccharide antigens

Caused by B. henselae

*Cat Scratch Disease* = relativel common, benign = localized lymphadenitis = 10% "atypical" disease = subacute endocarditis - other: CNS or bone - associated with cats (wild or often kittens) - causes transient bacteremia in cats - infected flea --> can transmit bacteria to other cats - possible fleas transmit to humans - seen as result of cat bite or scratch

(TEST) Antibiotic that is effective for gram-negative bacteria but ineffective for MRSA

*Ceftazidime, a third generation cephalosporin* - Ceftazidime (beta-lactam) + tobramycin (aminoglycoside) = P. aeruginosa treatment Third generation cephalosporins - cefdinir, cefixime, cefotaxime, ceftizoxime, ceftazidime, cefotaxime - *enhanced activity against gram-negative* organisms - high potency against H. influenza, N. gonorrhoeae, N. meningitides, Enterobacter, Salmonella, indole-positive Proteus, Serratia, E. coli - moderate activity against anaerobes - Ceftriaxone used for sexually transmitted infections caused by gonorrhea, as well as in empiric therapy for community-acquired meningitis - penetrate the CSF - used to treat gonorrhea, Lyme disease, meninigitis, serious hospital-acquired *gram-negative infections, alone or in combo with aminoglycoside*

(TEST): A cancer patient had septicemia with Pseudomonas aeruginosa & the organism was found to be resistant to ciprofloxacin & other fluoroquinolones. What would be a good therapy for this infection?

*Ceftazidime, a third generation cephalosporin, plus tobramycin*

Treatment of Gonorrhea

*Ceftriaxone + Azithromycin or Doxycycline* - uncomplicated cases Alternative: Cefixime + Azithromycin or Doxycline resistant to many antibiotics Ceftriaxone or erythromycine ointment for ophthalmia neonatorum Silver nitrate, tetracyline, or erythromycin ointment administered to eyes of neonates

Treatment of H. influenza

*Cephalosporins = systemic disease* - 3rd generation cephalosporins (cefotaxime or ceftriaxone) *Ampicillin = less severe disease* - ampicillin or amoxicillin can be used for less serious infections (otitis media) - ampicillin resistance is transmitted by plasmid from strain to strain - used to be drug of choice prior to dev't of resistance *Fluoroquinolones = alternative*

(TEST): Groups that may be seen in immigrants & returned overseas travelers but rarely or never acquired in the USA

*Chagas, Cysticercosis, Malaria* Malaria = fever, headache, anemia, splenomegaly - P vivax/ovale = 48-hour cycle (tertian; fever on first day & third day --> fever = 48 hours apart); formant form (hypnozoite) in liver - P falciparum = severe; irregular fever patterns; parasitized RBCs occlude capillaries in brain (cerebral malaria), kidneys, lungs - P malariae = 72-hour cycle (quartan)

Diseases caused by Haemophilus ducreyi (G- coccobacillus)

*Chancroid* Haemophilus ducreyi - *painful* genital ulcer - unilateral *painful* swollen inguinal lymph nodes rapidly develop in half of infected ppl - lymph nodes become matted & will rupture, releasing pus - gram-negative coccobacilli - isolation of culture of ulcer or infected lymph node = diagnostic - PCR mutiplex amplifies & detects bacterial DNA of Haemophilus ducreyi, Treponema pallidum, & herpes simplex 1 & 2 all at the same time Treatment - single dose treatment of 1-gram of oral azithromycin or 250 mg of intramuscular ceftriaxone

Vector of Scrub Typhus:; Orientia tsutsugamushi

*Chiggers* (larval stage of mites) - papule at bite site ulcerates --> becomes necrotic - evolves into *eschar* with *regional lymphadenopathy* - *macular-papular rash common* = spreads from trunk *centrifugally* to extremities (perivasculitis of small blood vessels) - headache, fever, myalgia, generalized lymphadenopathy in 8-10 days

Most common cause of Non-gonoccocal Urethritis (NGU) after E. coli & Staph. saprophyticus

*Chlamydia trachomatis* - Chlamydia trachomatis serotypes D-K - Urethritis *not* caused by Neisseria gonorrhoeae = gonococcal urethritis (NGU) = most common sexually transmitted disease - NGU predominately caused by Chlamydia trachomatis & Ureaplasma urealyticum - Empirically treated with antibiotics to cover Neisseria gonorrhoeae, Chlamydia trachomatis, Ureaplasma urealyticum - Treatment regimen = intramuscular ceftriaxone (Neisseria) followed by a 7-day course of oral doxycycline or 1 oral dose of azithromycin (Chlamydia & Ureaplasma)

(TEST): Vaginitis or cervicitis with vaginal discharge is often observed during infection with what group of organisms?

*Chlamydia trachomatis, Trichomonas vaginalis, Neisseria gonorrheoae*

(TEST): Vaginitis or cervicitis with a vaginal discharge is often observed during infection with which group of organisms?

*Chlamydia trachomatis, Trichomonas vaginalis, Neisseria gonorrhoeae*

Caused by L-1, L-2, L-3. Tender inguinal/femoral lymphadenopathy. Usually unilateral. Perinodal inflammation & bubo formation. Sometimes *proctocolitis (MSM)*. Bubos can be very painful!

*Chlamydia trachomatis: Lymphogranuloma venereum (LGV)* - small, painless ulcers on genitals --> swollen, painful inguinal lymph nodes that ulcerate (buboes) - treat with doxycycline - infected people become sero-positive

A patient who is a recent immigrant from a tropical, remote, rural area with no medical care is now working with a group of migrant crop harvesters. He has a large, raised, colored, cauliflower-like ankle lesion. Darkly pigmented, yeastlike sclerotic bodies are seen in the tissue biopsy. What is the most likely diagnosis?

*Chromoblastomycosis* / Chromomycosis = Phialophora , Fonsecea pedrosoi, P. compacta, P. verrucosa, Cladosporium carrionii = chronic fungal infection that *remains localized* = wart nodules, usually on *lower legs* = lesions enlarge & group with *small ulcerations (black dots)* - produce *characteristic sclerotic bodies (copper pennies)* = subcutaneous infection caused by variety of copper-colored soil saprophytes found on rotting wood - infection occurs following *puncture wound* - initially, small, violet wartlike lesion develops - over months to years: additional violet-colored wartlike lesions arise nearby - clusters of lesions resemble *cauliflower* - skin scrapings with KOH reveal copper-colored sclerotic bodies - occurs worldwide by more common in *tropical & subtropical regions* - varying success = amphotericin B, ketoconazole, itraconazole, saperconazole

Although hard to find in Lymphocutaneous sporotrichosis (Sporothrix schenckii) nodule, what would be present in the tissue?

*Cigar-shaped to oval yeasts* - dimorphic - treatment = itraconazole (cutaneous); amphotericin B IV (pulmonary, meningitis, disseminated); prophylaxis with NSAID

What form would Sporothrix schenckii present in tissue?

*Cigar-shaped to oval yeasts* Sporothrix schenckii - dimorphic, cigar-shaped budding yeast that grows in branching hyphae with rosettes of conidia - commonly found in soil & on plants (rose thorns & splinters) - occupational hazard for gardeners - subcutaneous nodule gradually appears --> becomes necrotic & ulcerates - culture at 37 C = yeast - culture at 25 C = branching hyphae (dimorphism) - treat with itraconazole, fluconazole, oral potassium iodide

(TEST): Which of the following drugs is often effective for treating Pseudomonas aeruginosa infections?

*Ciprofloxacin* *CAMPFIRE* *C*arbapenems *A*minoglycosides *M*onobactams *P*olymyxins *F*luoroquinolones Th*IR*d- & fourth-generation cephalosporins *E*xtended-spectrum penicillins (piperacillin, ticarcillin)

A 27-year-old woman comes to ED because of a 2-day history of abdominal cramps, vomiting, a low-grade fever, & 10 to 12 episodes of non-bloody diarrhea per day. She recently returned from a 1-week vacation in Mexico, & says that she primarily ate salads during her stay. Her temperature is 38.4 C (101.1 F), pulse is 112/min, BP is 119/78 mmHg, & respirations are 16/min. She has diffuse abdominal tenderness with no evidence of guarding or rebound tenderness. A stool sample shows presence of fecal leukocytes. Stool culture results are pending. The physician decides to prescribe an antimicrobial. What drugs should the patient receive as empiric treatment?

*Ciprofloxacin* - traveler's diarrhea likely to develop within 2-10 days after ingesting local water &/or eating fresh fruits & veggies (such as fresh salad) that could be been "washed off" with local water = 10 or more epiosdes of diarrhea per day - absence of blood in stool helps rule out organisms such as EHEC & amebiasis - most cases of traveler's diarrhea caused by ETEC, Shigella species, & Campylobacter jejuni - most commonly used agents to treat traveler's diarrhea = fluoroquinolones, such as ciprofloxacin, ofloxacin, & norfloxacin - trimethoprim/sulfamethoxazole most commonly used in treating children

(TEST): Fluoroquinolone often effective for Pseudomonas or E. coli but not useful for Streptococcus

*Ciprofloxacin* - does poorly against Streptococcus penumoniae - has activity against Staph. aureus & anthrax - don't cover anaeobes - used to treat patients with cystic fibrosis - used for diarrhea caused by E. coli, Salmonella, Shigella, Campylobacter

A patient has splotchy hypopigmentation on the chest & back with only slight itchiness. What is most likely to be seen on a KOH mount on skin scraping?

*Clusters of round fungal cells with short, curved, septate hyphae* Malassezia furfur - seen as clusters of round fungal cells with short, curved septate hyphae (spaghetti & meatballs appearance) - yeast-like fungus (not a dermatophyte despite being called a tinea) - degradation of lipids produces acids that damage melanocytes & causes hypopigmentated &/or pink patches - stratum cornum - back & chest - *cultures on blood agar + sterile olive oil*

(TEST): Which of the following produces spherules when growing in a human host at 37 °C?

*Coccidioides immitis* - Southwestern United States, California - causes pneumonia & meningitis - can disseminate to skin & bone - case rate increases after earthquakes (spores in dust thrown into air --> inhaled --> spherules in lung) - spherule filled with endospores Systemic fungal infections: histoplasma capsulatum, blastomyces dermatitidis, coccidioides immitis - dimorphic fungi - grow as mycelial forms, with spores, at 25 C on Sabouraud's agar - at 37 C on blood agar, they grow in yeast form --> inhaled by humans

A 15-year-old dirt-bike rider visiting California the first time has developed pneumonia. The causative organism has environment form that consists of hyphae that break up into arthroconidia, which becomes airborne. What is the agent?

*Coccidioides immitis* - causes mild pneumonia in normal people in southwestern US - common opportunistic infection in AIDS patients from that area - found in desert sand, primarily in arthroconidia & hyphae

A 15-year-old dirt-bike rider visiting southern California the first time has developed pneumonia. The causative organism has environmental form that consists of hyphae that break up into arthroconidia, which become airborne. What is the agent?

*Coccidioides immitis* - found in desert sand, primarily as arthroconidia & hyphae - causes mild pneumonia in normal people in southwestern US - common opportunistic infection in AIDS patients from area

(TEST): A lung biopsy from a patient who developed flu-like symptoms after participating in a cross-desert race in southern Arizona reveals the presence of spherules. The likely diagnosis is

*Coccidioidomycosis* - Southwestern United States, California - causes pneumonia & meningitis - can disseminate to skin & bone - case rate increases after earthquaes (spores in dust thrown into air --> inhaled --> spherules in lung - spherule (much larger than RBC) filled with endospores

(TEST): A 56-year-old patient with chronic obstructive pulmonary disease presented to the emergency department complaining of shortness of breath. His chest X-ray showed a right lower lobe infiltrate, and his O2 saturation was 80% on 2L. He was admitted to the intensive care unit as intubation could be required. He remained in the intensive care unit for 4 days. He did not require intubation but did need supplemental O2 . How is this type of pneumonia classified?

*Community acquired pneumonia*

(TEST): Detection of rising Ab titers in blood samples taken several weeks apart = important component of what organisms?

*Coxiella burnetii, Rickettsia prowazekii, Borrelia burgdorferi* Coxiella burnetii - infect monocytes/macrophages - infection of humans via inhalation - serology: IFA for IgG & IgM Ab to phase I (spore-liek) & phase II (large cell forms( Ag on *paired sera* = *Category B Bioterrorism Agent* Rickettsie prowazekii - Epidemic typhus - via body lice = *Typhus group* - centrifugal rash - trunk to extremities - *human to human* transmission - high fever, macular skin rash

(TEST): This obligate intracellular organism which causes an acute fever, severe headaches, malaise, myalgias, atypical pneumonia, and gastrointestinal distress is considered a Category B Bioterrorism Agent because it is highly infectious, transmitted by aerosols, and has spore-like forms resistant to heat and drying.

*Coxiella burnetti* (Q Fever) - has endospore form - resistance to heat & drying - spores may contaminate milk (pasteurization temps must be raised to greater than 60 C to kill endospores) - extracellular existence: can survive outside of host cell - grows in ticks & cattle - spores are aerosolized --> inhaled = human disease - mild pneumonia similar to Mycoplasma pneumonia often develops - only rickettsial disease that causes pneumonia & in which there is NO rash - mostly asymptomatic - can cause granulomatous hepatitis & "culture negative" endocarditis - treatment = doxycycline

A noncompliant, HIV-positive patient has been complaining of a stiff neck & severe headache. The headache was initially lessened by analgesics, but the analgesics are no longer effective. His current CD4+ count is 180/mm^3. He is not on any prophylacic drugs. What is the most likely causative agent?

*Cryptococcus* neoformans - encapsulated yeast - major causative agent of *meningitis in patients with AIDS* - 5-10 um with narrow budding - not dimorphic - found in soil, pigeon droppings - acquired via inhalation with hematogenous dissemination to *meninges* - culture on Sabouraud agar - highlighted in India ink & mucicarmine - latex agglutination test detects *polysaccharide capsular antigen* causes - cryptococcosis, *cryptococcal meningitis*, cryptococcal encaphalitis (soap bubble lesions in brain), primarily in *immunocompromised*

(TEST): Infection with this organism = profuse, large volume, watery diarrhea = life-threatening in HIV patients

*Cryptosporidium parvum* - outbreaks of diarrhea from contaminated municipal water sources & in infants in daycare centers - ingested as round oocyst that contains 4 motile sporozoites - life cycle in intestinal epithelial cells - immunocompromised = severe, protracted diarrhea that is life-threatening - treatment = nitazoxanide, paromomycin with or without azithromycin

(TEST): Which of the following protozoan parasites is a member of the Subclass Coccidia and is responsible for large-scale waterborne outbreaks, is clinically characterized by acute watery diarrhea, abdominal cramps, weight loss, fever, and vomiting of relatively short duration (5-10 days) that is effectively treated with nitazoxanide, and is transmitted by oocysts containing eight fully developed sporocysts that are passed in the stool?

*Cryptosporidium parvum* - severe diarrhea in AIDS - mild disease (watery diarrhea) in immunocompetent hosts - oocysts in water = transmission - oocysts in acid-fast stain - prevention (by filtering city water supplies) - treatment = nitazoxanide in immunocompetent hosts

Enterobacter: hospital-acquired neonatal sepsis; better to use single-dose antibiotics rather than multiple dose.

*E. cloaceae* - gram-negative, facultatively-anaerobic, rod-shaped - frequently grown at 30 C on nutrient agar or broth or at 35 in tryptic soy broth - peritrichous flagella - oxidase-negative & catalase-positive - member of normal gut flora - sometimes associated with urinary tract & respiratory tract infections - treatment with cefepime & gentamicin has been reported

(TEST): A 57-year-old male with a medical history of a gastric ulcer had recently noted symptoms of dyspepsia. Gastroendoscopy was performed and biopsy of the antral portion of the stomach was consistent with moderate gastritis. No tumor was seen. The biopsy also demonstrated 3+ to 4+ of a bacterial organism. If the suspect bacterial organism is Helicobacter pylori, then the bacterial organism seen on microscopic examination of the biopsied tissue should have which one of the following cellular morphologies?

*Curved or spiral rods* H. pylori - curved, terminally flagellated, gram negative rod - triple positive = catalase +, oxidase +, urease +

Characterized by uniform but diffuse attachment of bacteria to epithelium. Mediated by Dr-like fimbrial adhesin (like that in uropathogenic E. coli). Associated with diarrhea in children. Cases in literature show prevalence in Brazil.

*DAEC* (Diffusely Adhering E. Coli)

(TEST): Which of the following is a drug useful for treating a variety of antibiotic resistant gram-positive bacteria provided that the lungs are clear of infection?

*Daptomycin* - bactericidal - binds to & depolarizes cell membrane = loss of membrane potential & rapid cell death - active against vancomycin-resistant strains - may cause myopathy

(TEST): What symptoms and sequelae are indicative of hemolytic uremic syndrome (HUS)?

*Diarrhea & abdominal cramps, later followed by low platelet counts & reduced renal function* HUS - anemia, thrombocytopenia, renal failure (uremia) - associated with EHEC (E. coli 0157:H7) - secondary to infected hamburger meat often = reservoir for EHEC

(TEST): What symptoms and sequelae are indicative of hemolytic uremic syndrome (HUS)?

*Diarrhea and abdominal cramps, later followed by low platelet counts and reduced renal function* - Shiga-like toxin causes HUS = triad of anemia, thrombocytopenia, & acute renal failure via microthrombi forming on damaged endothelium --> mechanical hemolysis (with schistocytes on peripheral blood smear), platelet consumption, & decreased renal blood flow

(TEST): Exoenzyme A produced by Pseudomonas aeruginosa is a ribosylating toxin that inhibits protein synthesis. Which of the following is a toxin produced by a gram-positive bacterium with an analogous mechanism of action?

*Diphtheria toxin* - exotoxin A has same mechanism as diptheria toxin (stops protein synthesis) but is not antigenically identical

A patient whose major source of protein is smoked & cooked fish develops what appears to be pernicious anemia. What parasite is noted for causing a look-alike vitamin B12 anemia in certain genetically predisoposed infected individuals?

*Diphyllobothrium latum* - tapeworm associated with anemia - transmitted in fish found in cool lake regions - vitamin B12 deficiency (tapeworm competes for B12 in intestine) --> megaloblastic anemia - ingestion of larvae from raw freshwater fish - treatment = praziquantel

(TEST): Blastomycosis is a common infection in which one of the following animals in the endemic region?

*Dogs* Blastomyces dermatitidis - nature - males 40 to 60 y/o - via respiratory tract - frequents *wooded areas* - common infection in *dogs in endemic areas* - typically severe & often fatal - pulmonary, skin - dimorphic: mycelial phase at room temp --> can get to alveolar spaces - yeast at 37 degrees - begins as papulopustular lesion with microabscesses at edge

Diseases caused by Calymmatobacterium granulomatis (G- coccobacillus)

*Donovanosis* *Granuloma inguinale* - caused by Klebsiella granulomatosis/Calymmatobacterium granulomatis - ulcerative genital lesions

A 67-year-old woman with a history of renal disease comes to the physician because of fever, muscle pain, headache, & a circular rash with central clearing on her left thigh. Her temperature is 38.7 C (101.7 F), pulse is 101/min, respirations are 14/min, & blood pressure is 135/86 mmHg. She says that she was on a camping trip with her son & his fam in the northeast United States 7 days earlier. A review of her records shows previous severe allergic rxns to penicillin & to macrolides. What drugs is most appropriate for this patient?

*Doxycycline* - Lyme disease = most common vector-borne illness in US - multisystem bacterial illness caused by spirochete Borrelia burgdorferi - transmissted to humans via tick bites, from infected ticks of genus Ixodes - erythema migrans (target/bulls eye rash - carditis/heart block - can cause encephalomyelitis - *oral doxycycline, amoxicillin, & cefuroxime axetil* all have equivalent efficacy - doxycycline generally used since it is effective in treating anaplasma phagocytophilum = common coinfection agent - doxycycline has best penetration into CNS & is excreted largely by non-renal routes

Treatment of Coxiella burnetii, Q fever agent

*Doxycycline* Trimethoprim/Sulfamethoxazole - for allergic patients, pregnancy women *Doxycyline + Hydroxychloroquine* for chronic infection - prolonged treatment course (months/years) Q fever - no arthropod vector - spores inhaled as aerosols from cattle/sheep amniotic fluid - presents as pneumonia - most common cause of culture negative endocarditis

Chlamydia trachomatis: LGV Treatment

*Doxycycline* or erythromycin, 21 days Drainage of infected buboes in inguinal lymph nodes

(TEST): Treatment for HME - Human Monocytic Ehrlichiosis

*Doxycyline*

Cause majority of CNS infections in *infants < 1 month*

*E. coli & Group B streptococci* - 75% possess K1 capsular antigen = commonly present in GI tract of pregnant women & newborns - meningitis commonly treated with penicillin - Neonatal meningitis/E. coli caused by birth exposure to *encapsulate (primarily K1) strains of E. coli* *3 bacteria responsible for most meningitis acquired by baby coming out of birth canal (within first 3 months of age) = Listeria monocytogenes, E. coli, Group B streptococcus.* - 2 later bacteria cause meningitis later in life after maternal Abs passively given to fetus wane & before new Abs develop = Neisseiria meningitidis & Haemophilus influenza

Enterobacter: food-borne in powdered baby formula. Causes necrotizing enterocolitis, meningitis, and sepsis in neonates.

*E. sakazakii (now under genus Cronobacter)* - in infants, it can cause bacteraemia, meningitis, & necrotizing enterocolitis - gram-negative, rod-shaped, pathogenic bacterium

Most common virotype that produces disease in developed countries

*EHEC* - estimated 73,000 infections & 60 deaths per year in US - mild diarrhea, *hemorrhagic colitis* with severe abdominal pain, *bloody diarrhea*, little or no fever - more than 50 serogroups - most common in US = O157:H7 - secrete Shiga-like toxin / verotoxin - inhibit protein synthesis by inhibiting 60S ribosome = intestinal epithelial cell death

Occurs days to weeks after initial infection of Lyme disease.

*Early Disseminated Lyme Disease* = Stage 2 - *disseminated multiple erythema migrans* - *arthritis* in large joints - *neurological complications* = Bell's palsy; radiculoneuritis; meningitis/encephalitis - *cardiac complications* = AV block, myocarditis - inflammatory response to spirochetes - antibiotic treatment resolves disease = dissemination of Borrelia burgdoreferi spirochetes to 4 organs systems: skin, nervous system, heart, joints

Can occur in critically ill patients & usually seen in patients with bacteremia. Skin infection commonly attributed to P. aeruginosa. Roundish lesions with necrotic centers & erythematous edges. Bacterial invasion of vasculature = cause.

*Ecthyma Gangrenosum* - rapidly, progressive, necrotic cutaneous lesion - caused by *Pseudomonas* bacteremia - typically seen in immunocompromised patients

Gram-negative, non-spore forming rod. Facultatively anaerobic. Colonizes human oropharynx. Opportunistic pathogen. Most commonly isolated from human bite wounds or fistfight injuries. Subacute endocarditis. HAC*E*K. Sinusitis, meningitis, brain abscesses, pneumonia, lung abscesses.

*Eikenella corrodens* - usually susceptible to penicillin, ampicillin, cephalosporins, tetracyclines, fluoroquinolones. - corrodes agar - pits down into agar - grows into agar - hydrolyzes some of agar media HACEK = slow growing bacteria known to cause endocarditis - Haemophilus - Actinobacillus - Cardiobacterium - Eikenella - Kingella

2 distinct morphologic forms of Chlamydiaceae

*Elementary Body (EB)* - small, *infectious*, intracytoplasmic inclusion body - resistant to environmental stress - *transmits infection* *Reticulate Body (RB)* - larger, non-infectious - metabolically active - *replicating form*

Transmitted by soft ticks (Ornithodoros sp.), Tick-borne Relapsing Fever (TBRF). Short feeding (15-20 minutes) at night, rodent infested cabins. Less severe disease, untreated = 5-10% mortality. 30 cases/year in USA.

*Endemic*, B. hermsii, B. parkerii, & B. turicatae in USA - borrelia bacteria that cause TBRF = transmitted to human via soft ticks of genus Ornithodoros

(TEST): What organism is second only to malaria as a protozoan cause of mortality, may cause colitis as well as extra-intestinal infections of the liver and other organs, may cause colonic perforations with resulting peritonitis, and responds to treatment with metronidazole?

*Entamoeba histolytica* - amebiasis = bloody diarrhea (dysentery), liver abscess (anchovy paste exudate), RUQ pain - histology = flask shaped ulcer - cysts in water = transmission - serology &/or trophozoites (with engulfed RBCs in cytoplasm) - cysts with up to 4 nuclei in stool - treatment = metronidazole; iodoquinol for asymptomatic cyst passers

(TEST): Which of the following organisms is second only to malaria as a protozoan cause of mortality, is a cause of dysentery and colitis as well as extra-intestinal infections of the liver and other organs, may cause colonic perforations with resulting peritonitis, and responds to treatment with metronidazole and paramomycin?

*Entamoeba histolytica* = Amebiasis - *ingesting cysts* in fecally contaminated food or drink - fecal-oral transmission - infective cysts & trophs (loose stools) pass in feves - cysts survive in env't - dysentery / bloody diarrhea - "classic" flask-shaped ulcer - Amebic Liver Abscess (ALA) Treatment: - asymptomatic = *paramomycin* or iodoquinol - amebic colitis & amebic liver abscess = *metronidazole* or tinidazole (follow with luminal agent (*paramomycin* or iodoquinol) to eradicate colonization

(TEST): Ate hamburger at local venue. Two days layer = diarrhea. Symptoms worsening. Bloody diarrhea & abdominal cramping. Battery of tests = low platelet counts & reducing glomerular filtration. Diagnosed with HUS. What E. coli?

*Enterhemorrhagic* (EHEC) - hemorrhagic colitis - HUS = anemia, thrombocytopenia, renal failure triad - via shiga-like toxin - *hamburger meat*! - O157:H7 = most common serotype in US - via undercooked meat, raw leafy veggies

(TEST): A 27-year-old female presents to the emergency room with complaints of left flank pain, fevers and chills. She noted increased urinary frequency and foul-smelling urine on the day prior to admission. She presented with a temperature of 39.8º C and physical examination showed left costovertebral angle tenderness. Urinalysis of a clean-catch urine sample was notable for >40 white blood cells, 4 to 10 red blood cells and 4+ bacteria per highpower field. Urine culture was positive for >100,000 CFU of a lactose-positive gram-negative rod. Urine culture suggests that the etiological agent could be Escherichia coli or Klebsiella. What other bacterial agent could also be responsible?

*Enterobacter species* Lactose-fermenting enteric bacteria - fermentation of lactose --> pink colonies ojn MacConkey agar - *Klebsiella, E. coli, Enterobacter, & Serratia (weak fermenter)* - E. coli produces beta-galactosidase = breaks down lactose into glucose & galactose - EMB agar: lactose fermenters grow as purple/black colonies; E. coli grows with green sheen

NaCl broth test differentiates...

*Enterococcus from Group D streptococci* Enterococci - gram + - hardier than nonenterococcal group D - can grow in 6.5% NaCl & bile

Mass of fungal filaments is called

*Mycelium* = mass of intertwining hyphae - vegetative = grow into, penetrate medium - aerial = project above surface of medium: wind/draft --> can be infected

E. coli associated with infant diarrhea in developing countries

*Enteropathogenic (EPEC)* - produces bundle-forming pili & adhesin called intimin - attaches to enterocytes in SI = damages microvilli Enterotoxigenic (ETEC) - gram-negative, oxidase-negarive rods - reduce nitrates to nitrites - ferments both glucose & lactose - adheres to small intestine via pili & secretes 2 toxins - LT toxin = A-B toxin --> catalyzes ADP-ribosylation --> increases adenylate cyclase - ST toxin --> activates guanylate cyclase --> hypersecretion of fluids & electrolytes = heat-stable Enteroaggressive (EAEC) Diffuse-adhering E. coli (DAEC) - not in developing countries

E. coli associated with traveler's diarrhea

*Enterotoxigenic (ETEC)* - produces heat-labile & heat-stabile enterotoxins - no inflammation or invasion *Enteroaggressive (EAEC)*

Disease caused by R. prowazekii

*Epidemic typhus* = louse-borne typhus - vector = body lice (ticks) - reservoir = humans, *flying squirrels* - high fever, intense headache, rash (centrifugal) - diagnosis = serology - treatment = *doxy*, chlor, rif - flying squirrels = reservoir in Southern United States - abrupt onset of fever & headache following 2-week incubation period - small pink papules appear around 5th day on upper trunk --> quickly cover entire body - spares palms, soles, face - Rickettsia invade endothelial cells of blood vessels --> increased risk of gangrene of feet or hands - often resolves by 3 weeks

Lyme Disease: diagnostic symptom (70-80% patients). Characteristic expanding bulls-eye rash at site of tick bite that can be up to 30 cm across. Rash may be warm but non-pruritic, not painful. Inflammatory response to disseminating spirochetes.

*Erythema migrans* - may be misdiagnosed if no erythema migrans present

(TEST): Microorganism that is lactose-positive & produces indole

*Escherichia coli*

Pseudomonas lipase that disrupts host cell membranes. Found in cytotoxic (not intracellular) strains. Strains with this are associated with mortality in P. aeruginosa blood stream infections

*ExoU* - quickly kills host cell *(TEST): lipase activity --> quickly kills cell*

Responsible for *invasion* of P. aeruginosa into host cells. Injected into host by Type III secretion system (injectosomes). Trigger engulfment of bacteria. Bacteria grow intracellularly, spread to other cells, cause apoptosis.

*Exoenzymes S, T, & Y* = can be intracellular or cytotoxic ExoS & ExoT - induce host actin rearrangement for bacterial engulfment - can cause neutrophil apoptosis - inactivate Rho GTPases directly by Rho GAP (GTPase-activating protein) activity --> affects cytoskeletal rearrangement ExoS - also ADP-ribosylates early host proteins ezrin, radixin & moesin proteins (ERMs) --> affects cell shape,microvilli, motility, cell adhesion, phagocytosis, & actin regulation - ADP-ribosylase activity = blocks phagocytosis during pneumonia Exo T - ADP-ribosylates Crk protein --> inactivation of Rac = interferes with wound healing or phagocytosis ExoY - adenylate cyclase --> increases cAMP -->disrupts cell shape

Secreted from Pseudomonas. Same enzymatic function as diphtheria toxin (*ADP-ribosylates elongation factor 2 / EF-2*). Halts host protein synthesis & killing host cell.

*Exotoxin A* - secreted --> binds alpha-2-macroglobulin on host cell --> endocytosed in acidic vacuole --> nicked by host furin protease - active subunit released from vacuole --> traffics through ER/Golgi --> binds to host EF-2

A 50-year-old man is admitted to a psychiatric hospital after being detained by police for making inappropriate sexual advances. Psychiatric evaluation shows deficits in memory, insight, judgement, & social behavior. Over the next several years, he develops relaxed but expressionless facies, tremor, dysarthria, & pupillary abnormalities. Performing what studies on the patient's CSF will most likely confirm the diagnosis?

*FTA-ABS* = specific antitreponemal test - positive on both serum & CSF Neurosyphilis/General paresis - general paralysis of insane - late sequela of syphilitic infection = 5-20 yrs after infection = mental deterioration

(TEST): Groups of trematodes that produce adults inhabiting the intestinal tract of humans

*Fasciolopsis buski, Metagonimus yokogawai, Heterophyes heterophyes*

Classic triad of RMSF

*Fever, headache, rash* (ankles/wrists --> palms, soles, trunk, face) - 90% develop rash eventually - *Febrile illness* - Long-term effects via *vasculitis* - triad often not present when patient initially presents

Spread of Pelvic Inflammatory Disease (PID), like N. gonorrhea, into peritoneum causes

*Fitz Hugh Curtis Syndrome* - infection of liver capsule & "violin string" adhesions of peritoneum to liver - liver capsule inflammation --> adhesions

Drug that inhibits ergosterol synthesis, is important in treating Candida fungemias, & is used orally to suppress relapses of cryptococcal meningitis in AIDS patients?

*Fluconazole* - IV or oral - useful for oropharyngeal, isopharyngeal, & systemic candidiasis - also penetrates CSF - drug of choice for short-term & maintenance therapy of cryptococcal meningitis & for treatment of disseminated histoplasmosis & coccidioidomycosis - inhibits CYP34A & CYP2C9

Drug that inhibits ergosterol synthesis, is important in treating Candida fungemias, & is used orally to suppress relapses of cryptococcal meningitis in AIDS patients.

*Fluconazole* = imidazole: inhibits ergosterol synthesis - mainstay treatment of serious Candida infections - used to prevent relapse of fungal CNS infections in compromised patients

An 18-year-old man develops a headache 5 days after returning to military base from survival training in nearby countryside. Physical exam shows no abnormalities except for low-grade fever. Three days later, he develops a maculopapular rash that begins on hands and feet and spreads centripetally to involve the trunk. The vector for the most likely causal organism in this patient can also transmit what organism?

*Francisella tularensis* - patient has Rocky Mountain spotted fever (RMSF) via Rickettsia rickettsiae = gram-negative obligate intracellular bacterium with tropism for vascular endothelial cells - 3-12 days after tick bite - disease transmitted by wood tick, Dermacentor, which also transmits Francisella tularensis

Atypical pneumonia caused by...

*Mycoplasma pneumoniae* *Chlamydophila pneumoniae* Legionella species Viruses

Diseases caused by H. pylori

*Gastritis* *Peptic ulcers* *Risk factor for gastric carcinoma* Helicobacter pylori... = triple positive: catalase +, oxidase +, urease + - can use urea breath test or fecal antigen test for diagnosis - urease produces ammonia --> alkaline environment = help H pylori survive in acidic mucosa - colonizes mainly antrum of stomach = risk for peptic ulcer disease, gastric adenocarcinoma, MALT lymphoma - most common initial treatment = triple therapy = amoxicillin + clarithromycin + proton pump inhibitor

Most common form of salmonellosis (> 1 million per year in U.S.)

*Gastroenteritis* - symptoms in 6-48 hours = nausea, vomiting, non-bloody diarrhea, fever, cramps, headache - *S. typhimurium, S. enteritidis* = common culprits - poultry, eggs, pets, turtles = common sources - antibiotics not indicated

What species of Campylobacter is linked with development of Guillain-Barre syndrome (GBS)?

*Gastrointestinal infection with C. jejuni* - 1 case of GBS / 1,058 cases of C. jejuni Guillan-Barre Syndrome - autoimmune disorder of peripheral nervous system - symmetrical weakness - associated with *O:19* - may be due to antigenic cross-reactivity between LPS & peripheral nerve gangliosides - antibodies directed against Campylobacter LPS can damage neural tissue

(TEST): Antibiotic that most directly damages bacterial DNA & is bactericidal

*Gatifloxacin* - treats P. aeruginosa (fluroquinolone therapy) = 3rd & 4th fluoroquinolone - broader spectrum & enhanced activitity against G+

Small whitish bumps or groups of bumps that are usually flat, papular or pedunculated (on a stalk). Seen in HPV.

*Genital warts (condylomata acuminata)* - can be *painful & pruritis* depending on location - benign warty growth on genital skin - due to HPV type 6 or 11 - characterized by koilocyte change

An immunosuppressed patient has a white coating on his tongue (Candida). You do a Gram stain on the white exudate and find that it contains large Gram-positive budding yeast that are much larger than bacteria. What lab test will conclusively identify the etiologic agent to species?

*Germ tube formation after 2 hours incubation in media at 37 degrees C* Candida - dimorphic - forms pseudohyphae & *budding yeasts at 20 C, germ tubes at 37 C*

(TEST): Which of the following organisms is the most common intestinal protozoan parasite in the U.S., may cause diarrhea with flatulence, anorexia, cramps, epigastric pain, and fatty, yellow stool containing food chunks, and is associated with drinking unfiltered, mountain stream water?

*Giardia lambia* = giardiasis - bloating, flatulence, foul-smelling, fatty diarrhea - often seen in campers/hikers - fatty stools of Giardia - cysts in water = transmission - multinucleated trophozoites or cysts in stool - treatment = metronidazole

(TEST): Children at a Mississippi day care facility, their siblings, parents, and teachers come down with a short term attack of malabsorptive diarrhea with yellow-colored stools containing bits of undigested food. The most likely parasitic cause for these symptoms in this outbreak is

*Giardia lamblia* - *day care diarrhea* - sexually transmitted - bloating, flatulence, foul-smelling, fatty diarrhea - campers/hikers - cysts in water = transmission - *suction disk* attachment - Canada - multinucleated trophozoites or cysts in *stool* - treatment = metronidazole

(TEST): Which of the following groups contains only organisms that are primarily diagnosed by the identification of a characteristic stage of that parasite in the stool of an infected person?

*Giardia lamblia, Cyclopsora cayetanensis, Entamoeba histolytica*

A 55-year-old man develops water diarrhea with cramping and abdominal pain after returning from a vacation at the beach. He says that he consumed several meals consisting primarily of seafood, including lobster & raw oysters. What is most likely to be isolated from the stool of this patient?

*Gram-negative, curved rods isolated on alkaline medium* - patients with gastroenteritis following ingestion of raw oysters = V. vulnificus or V. parahaemolyticus

A 23-year-old man develops explosive, watery diarrhea with blood & mucus 3 days after eating undercooked chicken. Qualitative analysis of stool shows curved rods in the fecal smear, along with red blood cells & leukocytes. What lab tests is most appropriate to differentiate the pathogen responsible for these findings from other organisms?

*Growth at 42 C (107.6 F)* Campylobacter jejuni - pathogen that causes *enteric infection* associated with ingestion of raw or undercooked food products or through direct contact with infected animals - in the US, ingestion of contaminated poultry that has not been sufficiently cooked = most common means of acquiring infection - mean incubation period for C. jejuni = 3 days - initial symptoms = abrupt onset of abdominal pain & diarrhea - presence of fecal leukocytes = invasive infection - gram-negative rod with curved "comma shape" - can be selectively grown at 42 C (107.6 F) = inhibits growth of most other enteric bacteria - oxidase test distinguishes between Campylobacter, Neisseria, Helicobacter, & Vibrio (oxidase-positive) & Enterobacteriaceae (oxidase-negative) --> flood colonies with phenylenediamine --> black deposits = colonies produce cytochrome c - associated with Guillain-Barre syndrome - first-line treatment = fluoroquinolones or azithromycin -Campylobacter jejuni, ETEC, & Rotavirus = most common causes of diarrhea in the world

Leading cause of pediatric antibiotic usage

*H. influenza* - type b capsule commonly associated with invasive Haemophilus influenza disease in children, such as meningitis, epiglottitis, & septic arthritis - nontypeable/nonencapsulated strains frequently cause otitis media in children - antibodies to capsule are lacking in infants & children between 6 months & 3 years of age - mother possesses Abs against b capsule, which she has acquired in her lifetime --> she passes these Abs to fetus transplacentally & in her breast milk --> these "passively" acquire Abs last 6 months - *takes 3-5 years of H. influenza colonization & infection for children to develop their own Abs --> there is a window during which children are sitting ducks for invasive H. influenzae* - H. influenza type b = most common cause of septic arthritis in infants - 3rd generation cephalosporin = drug of choice for serious infections - ampicillin & amoxicillin can be used for less serious infections, such as otitis media

Used to subdivide Vibrio species into serogroups

*O-polysaccharides of Vibrio's LPS* - more than 140 serogroups of V. cholerae (O1 - O140) - 7 serogroups of V. vulnificus - 13 serogroups of V. parahaemolyticus

(TEST): Effective human vaccine is available for what microorganism?

*Haemophilus influenza* Hib capsule vaccine - key = stimulating early generation of protective Abs in young children - H. influenza capsule polyribitol ribose phosphate (PRP) conjugated with mutant diphtheria toxin protein, a Neisseria meningitides outer membrane protein, or tetanus toxoid to active T-lymphocytes & Abs against b capsule Ags - vaccination with Hib capsule of children in US at ages 2, 4, 6, & 15 months (along with DPT & polio vaccines)

(TEST): A 57-year-old male who quit smoking a year ago has chronic obstructive pulmonary disease (COPD). He presents to the emergency department with a productive cough with phlegm that has persisted for 48 hours. Which one of the following microorganisms is the likely cause of his current exacerbation?

*Haemophilus influenza* - patients with COPD get frequent infections with nontypeable H. influenzae --> worsens wheezing, shortness of breath & cough (COPD exacerbation) - small rods - X factor (hemin) & V factor (NAD) required for growth - obligate human parasite - LOS toxin - growth on choclate agar - cephalosporin for systemic disease - ampicillin for less severe - Hib conjugate vaccine stimulates T-dep immunity, enhanced Ab production (conjugate to diphtheria toxoid) - Rifampin prophylaxis for close contacts - *Satellite phenomenon* = will grow on blood agar as satellite of other bacterial colonies

(TEST): Human monocytic ehrlichiosis (HME) is transmitted by which type of arthropod vector?

*Hard ticks*

(TEST): Vector of RMSF in MS

*Hard ticks* - presents within week after person is bitten by either the wood tick Dermacentor andersoni or the dog tick Dermacentor variabilis - organisms proliferate in endothelial lining of small blood vessels & capillaries = small hemorrhages & thrombi

Vaccine of H. influenza

*Hib conjugate vaccine (capsule sugar = polyriobsylribitol phosphate: PRP)* - polysaccharides not immunogenic in young children - conjugate to protein carrier to elicit protective immune response polysaccharide conjugate vaccine... - stimulates T-dependent immunity - enhanced Ab production, especially in young children - repeat doses elicit booster response - 3 doses for children to 6 months of age - booster at 12-15 months

(TEST): If the production of a protein toxin (e.g. an enterotoxin) by Escherichia coli required a high cyclic-AMP level, which of the following carbon sources would be best for abundant toxin production?

*Histidine*

Laboratory diagnosis of human fungal infections depends on which three basic approaches?

*Histopathologic* *Immunologic* *Microbiologic* Lab diagnosis depends on *HIM* Media used for isolation = Sabouraud agar

A normally healthy 8-year-old boy from Florida is visiting friends on a farm in Iowa during the month of July. He presents on July 28 with a fever, cough, & lower respiratory symptoms (no upper respiratory tract symptoms). He has been ill for 4 days. His chest sounds are consistent with pneumonia, so a chest radiograph is obtained. The radiograph shows small, patchy infiltrated with hilar adenopathy. His blood smear shows small, nondescript yeast forms inside monocytic cells. What is the most likely causative agent?

*Histoplasma capsulatum* - histoplasma & blastomyces are both endemic in Iowa (central US bordering the MS River), but only Histoplasma = facultative intracellular parasite circulating in the reticuloendothelial system

How are resistance islands acquired in Acinetobacter?

*Horizontally - from other organisms* - not acquired as single element Acinetobacter - gram-negative - oxidase-negative & nonmotile - soil organisms - key source of infection in debilitated patients in hospital - bacteremia, UTIs, secondary meninigitis, infective endocarditis, wound & burn infections Capacity to develop resistance against many available antibiotics - possess resistance against broad-spectrum cephalosporins, beta-lactams, aminoglycosides, quinolones - resistance to variety of disinfectants - antibiotic resistance genes often plasmid-borne --> plasmids present in Acinetobacter strains can be transferred to other pathogenic bacteria via *horizontal gene transfer*

Scientific name for fungal cross wall

*Hypha* - cross wall of hypha = septum / septation - threadlike, branching, cylindrical, tubules composed of fungal cells attached end to end - grow by extending in length from tips of tubules

A patient presents with a circular, itchy, inflamed skin lesion that is slightly raised; it is on hist left side where his dog sleeps next to him. His dog has had some localized areas of hair loss. The patient has no systemic symptoms. What would you expect to find in a KOH of skin scrapings?

*Hyphae with little branching but possibly with some hyphae breaking up into arthroconidia* Ringworm from dog - dermatophytes = hyphae & arthroconidia Tinea corporis - occurs on torso - erythematous scaling rings (ringworm) & central clearing - can be acquired from contact with infected cat or dog

(TEST): Is this ok? A 7-year old girl developed signs of a urinary tract infection and a clean catch urine sample was sent to the lab. A Gram stain showed gram-negative rods in singles, several bacilli per oil immersion field. There were no signs of a urinary complication and there was no drug allergy. The girl was prescribed ciprofloxacin and the mother was instructed to call if her daughter was not better within 48 hours.

*Inappropriate antibiotic therapy, administer no antibiotic* - contraindicated in children! = bone, teeth (brown) Ciprofloxacin - highly active against gram-negative bacteria & moderately active against gram-positive bacteria Urethritis - ceftriaxone + azithromycin or doxycycline Cystitis - nitrofurantoin, trimethoprim/sulfamethoxazole, or fosfomycin

(TEST): Is this ok? A patient developed a soft tissue and bone infection of his foot, with drainage of foul-smelling pus. A gram stain of the pus showed gram-negative pleiomorphic bacteria in a variety of arrangements. When the infection was first detected, the patient was started on IV nafcillin and now a decision was made to continue this therapy plus treat also with IV gentamicin.

*Inappropriate antibiotic therapy, change therapy immediately* Nafcillin / penicillinase-resistant penicillin - MSSA Gentamicin - active against Enterobacter, indole-positive Proteus, Pseudomonas, Klebsiella, Serratia, among other gram-negative organisms - used synergistically in combo with beta-lactam antiobiotics or vancomycin for serious infections that require broad coverage

(TEST): What are the effects of Trichomonas vaginalis infection of the mother on pregnancy?

*Increased risk of premature birth* Trichomonas vaginalis - foul-smelling, greenish discharge - *trophozoites (motile)* - *strawberry cevix* - transmitted sexually - itching (pruritus), burning on urination, copious vaginal secretions - thin, watery, frothy, malodorous discharge in vaginal vault - *wet mount* - *metronidazole*

(TEST): What test would be used to distinguish Escherichia coli from Klebsiella & Enterobacter?

*Indole*

(TEST): Proteus can cause urinary tract infections that are complicated by which of the following?

*Induction of stone formation due to pH changes*

How is Ascaris acquired?

*Ingestion of food contaminated with eggs* - fertilized Ascaris eggs released in feces may contaminate food or water --> consumed - doesn't attach to intestine but maintains its position by mobility - worm may become hypermotile --> migrates into appendix or bile duct

(TEST): Acinetobacter baumannii is well adapted to the hospital environment. Which one of the following is thought to play a role in the ability of A. baumannii to persist in the hospital?

*It's ability to form biofilm* - complex surface associated communities - structural heterogeneity - composed of single or multiple species

Flue-like symptoms due to mass killing of T.p. by antibiotic (releases lipoproteins)

*Jarisch-Herxheimer reaction* - flu-like syndrome (fever, chills, headache, myalgia) after antibiotics are started - due to killed bacteria (usually spirochetes) releasing toxins

Klebsiella that does not grow outside of cells in vitro

*K. granulomatis* - take tissues or scrapings, stain with Giemsa or Wright's stain - appearance of small rods in cytoplasms of histiocytes, PMNs, & plasma cells = *Donovan bodies*

Patient presents with paranasal swelling & bloody exudate form both his eyes & nares, & he is nearly comatose. Necrotic tissue in the nasal turbinates show nonseptate hyphae consistent with Rhizopus, Mucor, or Absidia (phylum Zygomycota, class Phycomycetes). What is the most likely compromising condition underlying this infection?

*Ketoacidosis diabetes* - spores can germinate in sinuses - tissue invasion by hyphae - tissue necrosis & invasion of blood vessels - fungus can penetrate cerebral tissue Zygomycota - *susceptibility via diabetic ketoacidosis, burn victims, leukemia* = aseptate fungi - primarily in ketoacidotic diabetic patients & cancer patients = Rhizopus (bread mold), Mucor (shower curtain), Absidia - saprophytic molds - invade immunocompromised host - rapid growing - rhinocerebral, pulmonary, cutaneous, GI - inhaled spores colonize nasal passage or respiratory tract - cutaneous via direct inoculation of abraded skin - nonseptate hyphae - broad irregular walls; right angle branching - spores contained within sporangium - can have involvement of orbit with protrusion of eye!

A patient presents with paranasal swelling & bloody exudate from both his eyes & nares, & he is nearly comatose. Necrotic tissue in the nasal turbinates show nonseptate hyphae consistent with Rhizopus, Mucor, or Absidia (phylum Zygomycota, class Phycomycetes). What is the most likely comproising condition underlying this infection?

*Ketoacidotic diabetes* Zygomycota = aseptate fungi that cause serious infection, primarily in *ketoacidotic diabetic patients & cancer patients* - mucor = shower mold; rhizopus = bread mold - *irregular, broad, nonseptate hyphase branching at wide angles* - fungi proliferate in blood vessel walls, penetrate cribriform plate, & enter brain - rhinocerebral, frontal lobe abscess - cavernous sinus thrombosis - treatment = *amphotericin B*, surgical debridement

Invasive infection seen in children six months to four years. Infection of joints and bones. Infrequent bacteremia. Most infections have mild to moderate clinical signs. Often confused with other clinical conditions.

*Kingella kingae* - gram-negative coccobacillus - colonizes human oropharynx - opportunistic pathogen - subacute endocarditis, HACE*K* - usuaully susceptible to: penicillins, tetracyclines, erythromycin, fluoroquinolones, & aminoglycosides: FATE P

(TEST): A 72-year-old male recently died from pneumonia. Prior to death, he was coughing up blood, and sputum cultures contained gram-negative bacilli that produced pink colonies when grown on MacConkey agar. Post-mortem histopathology of lung tissue showed necrosis in the alveolar spaces and cavity formation. The likely cause of this man's pneumonia was

*Klebsiella pneumoniae* - NDM-1: metallo-beta-lactamase-1 = resistance to broad range of beta lactamse - endemic in Vietnam - copious, mucoid capsule - causes typical pneumonia - common cause of liver abscesses in alcoholics

(TEST): A 25-year-old male who is visiting the U.S. from Vietnam presents with granulomatous lesions on his genitals and in the groin area. He said that the lesions began as nodules under the skin. You send scraped portions of the affected tissue to the hospital laboratory and order a Giemsa stain. The stain shows small bacteria in the shape of rods inside the polymorphonuclear leukocytes (PMNs) of the tissue. Which of the following genera is the etiologic agent of your patient's infection?

*Klebsiella* - pneumonia, wound infections, soft tissue infections, UTIs, liver abscesses in alcoholics & diabetics, granulomatous disease of nose, granulomatous disease of genitals or inguinal (groin) area (granuloma inguinale / donovanosis) K. granulomatis = endemic in Papua New Guinea, Caribbean, South America, India, southern Africa, *Vietnam*, Australia - via repeated exposure via sexual intercourse or nonsexual trauma to genitalia - prolonged incubation (weeks or months) - subcutaneous nodules that break down & reveal granulomatous lesions - appearance of small rods in cytoplasms of histiocytes, PMNs, & plasma cells = *Donovan bodies*

Most cases of Legionella in the US are caused by

*L. pneumophilia* - serogroup 1 (*Lp-1*) - culture on *charcoal yeast extract agar* - *facultative intracellular* parasite - environment-related - severe respiratory infection

Inguinal bubos (swelling of lymph node) frequently associated with

*LGV* & *chancroid* - flunctuant lymph nodes can be aspirated through healthy skin Lymphogranuloma venereum - small, painless ulcers on genitals --> swollen, painful inguinal lymph nodes that ulcerate (buboes) - treat with doxycycline Chancroid - painful genital ulcer with exudate, inguinal adneopathy - haemophilus ducreyi - treat with azithromycin

(TEST): A 57-year-old male with a medical history of a gastric ulcer had recently noted symptoms of dyspepsia. Gastroendoscopy was performed and biopsy of the antral portion of the stomach was consistent with moderate gastritis. No tumor was seen. The biopsy also demonstrated 3+ to 4+ of a bacterial organism. What noninvasive test could have been performed to demonstrate the presence of Helicobacter pylori?

*Labeled urea/CO2 breath test* H. pylori - curved, terminally flagellated, gram negative rod - triple positive = catalase positive, oxidase positive, urease positive - *can use breath test or fecal antigen test for diagnosis* - urease produces ammonia = creates alkaline environment --> helps H. pylori survive in acidic mucosa - colonizes mainly antrum of stomach - causes gastritis & peptic ulcers (especially duodenal) - risk factor for peptic ulcer disease = peptic ulcer disease, gastric adenocarcinoma, MALT lymphoma - most common initial treatment = triple therapy = Amoxicillin (metronidazole if penicillin allergy) + Clarithromycin + Proton pump inhibitor (Antibiotics Cure Pylori); *tetracycline*

23-year-old man develops dehydration, & profuse, watery diarrhea 3 weeks after arriving in Mexico. He continues to have diarrhea despite not eating. Qualitative analysis of stool shows few leukocytes, trace mucus, & no blood. The causal agent produces a toxin with a mechanism of action that is closes to the mechanism of action of what organism?

*Labile toxin of Escherichia coli* - this is *cholera* --> *acute secretory diarrheal condition* caused by *toxin producing strains of Vibrio cholerae* = highly motile, halophilic, curved, gram-negative rod - pathogenic strains of Vibrio cholerae O1 & O139 = 2 primary virulence factors = cholera enterotoxin & toxin co-regulated pilus - cholera enterotoxin activates adenylate cyclase via ADP ribosylation of GTP-binding protein in small intestinalcrypt cells --> massive secretion of isotonic fluid - Enterotoxigenic E. coli produces toxin similar to cholera toxin, heat-stabile toxin - Heat labile toxin (LT) produces ETEC --> stimulates adenylate cyclase by ADP ribosylation of GTP binding protein = promotes secretion of fluid & electrolytes from intestinal epithelium

Quorum sensing regulation in P. aeruginosa via

*Las & RhI*

60% of untreated Lyme Disease infections.

*Late Disseminated (Untreated) Lyme Disease* - months to years after infection - *intermittent arthritis* with pain, swelling - usually single joint affected - *chronic arthritis* - *chronic neurological disorders* (5%) - *cognitive defects* - sleep disturbance, fatigue

Lectin on surface of P. aeruginosa. Preferentially binds host globotriaosylceramide (Gb3 or CD77). Binding induces host giant unilamellar vesicles (GUVs) to engulf bacteria. Independent of host actin

*LecA*

10% of pneumonia in adults. <1% of pneumonia in children. No milder cases. Mostly immunocompromised.

*Legionnaires' Disease* - pneumonia potentially fatal - severe pneumonia (often unilateral & lobar), fever, GI, & CNS symptoms - common in *smokers* & in chronic lung disease Legionella pneumophila - gram negative rod - gram stains poorly - use *silver* stain - grow on *charcoal* yeast extract medium with *iron* & *cysteine* - detected by presence of antigen in urine - labs = hyponatremia - aerosol transmission via env't water source habitat - treatment = macrolide or quinolone

(TEST): A 40-year-old serviceman who recently returned from a tour of duty in the Middle East presented to his physician with a lesion on his arm. About 6 weeks prior, he had noticed a small, red area on his arm. There was some pain and itching and over the next few weeks the area increased in size and eventually ulcerated. The lesion measured about an inch in diameter and although serous there was little drainage. The ulcer has a moist base and raised borders. His medical history was otherwise unremarkable; he indicated he was feeling well and had not had any fever, chills, anorexia, or weight loss. Which parasite is the most likely to account for these symptoms?

*Leishmania tropica* - carried by rodents, dogs, foxes - transmitted to humans by bite of *sandfly* - leishmaniasis found in South & Central America, Africa, & Middle East - spectrum of disease severity: single ulcer that will heal without treatment; to widely disseminated ulcerations of skin & mucous membranes; to very severe infection striking deep into reticuloendothelial organs, spleen & liver Cutaneous Leishmaniasis - sandfly --> skin --> migrate to reticuloendothelial cells --> skin ulcer develops = oriental sore

What V. cholerae serogroups produce cholera toxin?

*O1 & O139* - associated with cholera epidemics - cholera toxin = hypersecretion of electrolytes & water - toxin co-regulated pilus = adherence to intestinal mucosal cells; binding site for CTX - accessory cholera enterotoxin = increases intestinal fluid secretion - zonnula occludens toxin = increases intestinal permeability - neuraminidase = modifies cell surface to increase GM1 binding site for cholera toxin

(TEST): Group of organisms in which infection can produce splenomegaly, anemia and fever.

*Leishmonia donovani, Plasmodium falciparum, Babesia microti* Leishmania donovani - young malnourished children - invasion of reticuloendothelial cells of spleen & liver = hepatomegaly & massive splenomegaly - severe anemia - high titer antileishmanial IgG levels Babesia microti - via Ixodes scapularis (same as Lyme disease) - sporozoites invade erythrocytes --> differentiate into pear or ring-shaped trophozoites --> asexually bud --> divide into 4 merozoites = stick together = x-shaped tetrad/Maltese cross Plasmodium Falciparum - spleen & liver enlarge as fixed phagocytic cells (of reticuloendothelial system) pick up large amounts of debris form destroyed RBCs --> enlarged spleen occasionally ruptures

(TEST): Weil syndrome, severe disseminated disease with multi-organ involvement, is a complication of infection with this spirochete which is spread by contact with water, soil, or food contaminated with rodent urine

*Leptospira interrogans (Leptospirosis)* - Weil's Syndrome = infectious jaundice = involves renal failure, hepatitis with jaundice, mental status changes, hemorrhage in many organs

Disease caused by Leptospira interrogans

*Leptospirosis, Weil's Syndrome* - contact with rodent urine in food, soil, water - reservoirs = rodents, cattle, dogs, pigs, horses Leptospirosis - spirochete found in water contaminated with animal urine - flu-like symptoms, myalgias, jaundice, photophobia with conjunctival suffusion - prevalent among surfers/Hawaii Weil disease - icterohemorrhagic leptospirosis - severe form = jaundice, azotemia via liver & kidney dysfunction, fever, hemorrhage, anemia

Vector of *HME* - E. chaffeensis

*Lone Star tick (Amblyomma)* - reservoirs = deer, domestic dogs Ehrlichiosis, Human Monocytic - monocytes with morulae - mulberry-like inclusions in cytoplasm - high incidence in males > 60 y/o - treatment = doxycycline

(TEST): The serogroup of the Legionella pneumophila that most often causes infections in the United States is

*Lp-1* - urine antigen test only detects L. pneumophila serogroup 1 = 90% of cases

Most common *tickborne* illness in N. America & Europe

*Lyme disease caused by spirochete, Borrelia burgdorferi* = 20-30 um long by 0.2-0.5 um wide - gram-negative, spirochete bacteria - alters proteins on outer coat --> evades host immune response - *paucity & changing of surface proteins limits host immune response*

Diseases caused by Chlamydia trachomatis Serogroups L-1, L-2, L-3 (G- pleomorphic bacteria)

*Lymphogranuloma venereum (LGV)* - small, painless ulcers on genitals --> swollen painful inguinal lymph nodes that ulcerate (buboes) - treat with doxycycline

Chlamydia trachomatis: - easily induced cervical bleeding - vaginal discharge - vaginal bleeding - abdominal pain - dysuria

*MPC - Mucopurulent/Purulent* - endocervical discharge in endocervical canal

Flagellum of Pseudomonas binds to

*MUC1* ectodomains on airway epithelial cells = mucin-1: transmembrane glycoprotein - can be cleaved by either bacterial or host neuraminidases --> exposes more binding sites for bacteria to attach = precedent for bacterial invasion of airway epithelium

Diagnostic test useful in finding Salmonella or Shigella in stool specimens

*MacConkey Agar: Differential test* - mixed culture of lac- & lac+ - useful for diarrhea diseases *Both Salmonella & Shigella = gram-negative rods, non-lactose fermenters, oxidase negative, & can invade GI tract via M cells of Peyer patches*

E. coli rapidly grows on what media?

*MacConkey* - enteric pathogens, except EHEC, detected only in reference labs - culture on MacConkey, then assay for toxin with commercial immunoassay kits - many O157 strains do not ferment sorbitol --> sorbitol-containing MacConkey agar can be used a screening tool - EIEC difficult to distinguish because large virulence plasmid can get lost in vitro

(TEST): Drug often prescribed for out-patients with upper respiratory tract infection

*Macrolide* - atypical pneumonias (Mycoplasma, Chlamydia, Legionella), STIs (Chlamydia), gram positive cocci, B pertussis

A premature infant on intravenous nutrients & high-lipid fluids has developed septicemia that cultures out on blood agar only when overlaid with sterile olive oil. What is the most likely causative agent?

*Malassezia* Tinea (pityriasis) versicolor - caused by Malassezie (Pityrosporum species), a yeast-like fungus - degradation of lipids = acids that damage melanocytes = hypopigmented &/or pink patches - more common in summer - spaghetti & meatballs appearance on microscopy - treatment = selenium sulfide, topical &/or oral antigunfal medications - extreme = *ketoconazole, itraconazole* - stratum corneum - back & chest

Ehrlichiosis & Anaplasmosis has highest incidence in what patients?

*Males >60* - commonly diagnosed in adults - incidence increasing Ehrlichiosis - vector = tick - monocytes with morulae (mulberry-like inclusions in cytoplasm) Anaplasma - vector = tick - granulocytes with morulae in cytoplasm *MEGA berry* *M*onocytes = *E*hrlichiosis *G*ranulocytes = *A*naplasmosis = Rickettsial diseases & vector-borne illnesses - treatment for all: doxycycline

(TEST): Treatment for pinworm infection

*Mebendazole* - Treatment = albendazole, mebendazole, pyrantel, pamoate - avoid scratching - change sheets daily Enterobius vermicularis / Pinworm - simple life cycle: eggs ingested --> pinworms mature in cecum & ascending large intestine - female migrates to perianal area (usually at night) to lay her eggs --> become infectious 4-6 hours later - infection = severe perianal itching - diagnosis by placing scotch tape firmly on perianal area --> will pick up eggs = viewed under microscope - no eosinophilia since there is no tissue invasion

(TEST): Which of the following drugs is used in the treatment of Plasmodium vivax malaria in order to eliminate the dormant liver hypnozoite stages of the organism?

*Primaquine phosphate*

(TEST): An E. coli isolate from a urinary tract infection was found to be resistant to multiple antibiotics, but susceptible to trimethoprim. Another lab found that the organism was resistant to trimethoprim. The labs used the same methods except the one that found it resistant to trimethoprim used a medium enriched with yeast extract. Which of the following explains the findings?

*Medium with yeast extract provided the end product of the pathway blocked by trimethoprim* Trimethoprim - looks like dihydrofolate reductase of bacteria & competitively inhibits reduction - inhibits bacterial DNA formation

(TEST): Which one of the following virulence factors of Neisseria meningitidis contains lipooligosaccharides (LOS) and surface proteins and can protect the bacterial cells from antibodies directed against LOS?

*Membrane blebs*

Sepsis (with or without meningitis). Multiorgan involvement. Petechial skin lesions coalesce into larger hemorrhagic lesions. Disseminated intravascular coagulation with shock.

*Meningococcemia* - intravascular multiplication of Neisseria meningitidis = abrupt onset of spiking fevers, chills, arthralgia (joint pains), muscle pains, petechial rash - patients usually look acutely ill - once in bloodstream --> meningococci rapidly disseminate throughout body - can lead to meninigitis &/or fulminant meningococcemia - pic = hemorrhagic bullae - shock, DIC, purpura fulminans (15-25%) *Fulminant meningococcemia / Waterhouse-Friderichsen syndrome* - *septic shock* - bilateral hemorrhage into adrenal glands --> adrenal insufficiency - abrupt onset of hypotension & tachycardia, along with rapidly enlarging petechial skin lesions - DIC & coma may develop - death can occur rapidly (6-8 hours)

(TEST): Treatment for trichomoniasis

*Metronidazole*

(TEST): Treatment for amebic liver abscess (Entamoeba histolytica infection)

*Metronidazole* - Entamoeba histolytica, Giardia lamblia, Trichomonas vaginalis, anaerobic cocci & bacilli including Bacteroides fragilis, C. difficile & Gardnerella vaginalis Entamoeba histolytica - pseudophilia - homosexual men commonly asymptomatic carriers - *Acute Dysenteric Amebiasis (ADA) / Amebic Liver Abscess (ALA) = METRONIDAZOLE* - asymptomatic = paramomycin

Treatment for Bacterial Vaginosis

*Metronidazole* - trichomonas, giardia lamblia, bacterial vaginosis

Trichomoniasis Treatment

*Metronidazole* or tinidazole

(TEST): Which one of the following is considered the infective particle when inhaled from Histoplasma capsulatum?

*Microconidia* Histoplasmosis - associated with bat, chicken, & bird droppings especially starlings - via respiratory tract - *reactivation* of old foci can occur (immunosuppression) - Ohio Valley - phagolysosome fusion - raises pH to 5.5-6.5 Dimorphic: - mycelial in env't (with tuberculated macroconidia) - *microconidia are infective* yeast phase at 37 degrees - histoplasmin skin test

(TEST): These tiny intracellular gram-positive staining fungi produce acid-fast spores that infect other cells using polar tubules. Infections by these organisms produce significant symptoms only in immunosuppressed patients.

*Microsporidia species* = parasite of immunosuppressed - ubiquitous, obligate intracellular parasites - extensive host range = insects - mammals - via ingestion or inhalation of spores - gram positive, *acid-fast*, spores - thick chitinous walls - coiled polar tubules = polarity - sporoplasms injected into host cells by polar tubules - sporoplasma undergoes extensive multiplication either by merogony (binary fission) or schizogony (multiple fission)

(TEST): Transmits rickettsialpox

*Mites* Rickettsialpox/Rickettsie akari - transmitted to humans via *mites* that live on louse mice = mild, self-limited, febrile disease that starts with initial localized red skin bump (papule) at the site of the mite bite - bump turns into blister (vesicle) & days later fever & headache develop --> other vesicles appear over body (similar to chickenpox) - doxycycline

(TEST): Which one of the following bacteria produces beta-lactamase and can cause acute otitis media in young children?

*Moraxella catarrhalis* - causes 2 major diseases: otitis media & upper respiratory infection in patients with COPD or emphysema or in elderly - otitis media occurs in 80% of all children by age 3

(TEST): An 18-month-old presents with signs of acute otitis media. A course of amoxicillin fails to clear the infection. Which one of the following beta-lactamase positive bacteria would be a likely cause of the infection?

*Moraxella catarrhalis* - diplococci - aerobic - oxidase positive - commensals of human respiratory tract - opportunistic - most strains produce *beta-lactamase* - adhesins - inactivates complement - biofilm (in otitis media) = 3rd leading cause of *otitis media* in young children - bronchitis & bronchopneumonia in eldely - exacerbates COPD

(TEST): A 56-year-old patient with chronic obstructive pulmonary disease presented to the emergency department complaining of shortness of breath. His chest X-ray showed a right lower lobe infiltrate, and his O2 saturation was 80% on 2L. He was admitted to the intensive care unit as intubation could be required. He remained in the intensive care unit for 4 days. He did not require intubation but did need supplemental O2. Sputum samples obtained in the ER showed Gram-negative diplococci. What is the likely pathogen?

*Moraxella catarrhalis* - otitis media & uppe respiratory infection in patients with COPD or emphysema - COPD exacerbations - also cause pneumonia in the elderly

(TEST): Transmits Dengue fever (Breakbone fever)

*Mosquitos* Dengue fever - mosquito-borne febrile disease that occurs primarily in tropics but has worldwide distribution - *painful* illness - called break-bone fever because of severe painful backache, muscle & joint pain, & severe headache

(TEST): Vector of filariasis (Wuchereria or Brugia infection)

*Mosquitos* Wuschereria bancrofti & Brugia malayi - lymphatic infection - chronic leg swelling - Pacific Islands & Africa - transmitted microfilariae mature into adults within lymphatic vessels & lymph nodes of genitals & lower extremities - areas become covered with thick, scaly skin - chronic disfiguring = elephantiasis - blood drawn at night time - treatment = diethylcarbamazine

(TEST): The exotoxin A of Pseudomonas aeruginosa, as well as the products of its exoS and exoT genes, mediates a ribosylation reaction that includes the cleavage of

*NAD* Toxin A of P aeruginosa - same enzymatic function as *diphtheria toxin* (ADP *ribosylates* elongation factor 2 / EF-2 - halts host protein synthesis & killing host cell - secreted --> binds alpha-2-macroglobulin on host cell --> endocytosed in acidic vacuole --> knicked by host furin protease --> active subunit release from vacuole --> trafficks through ER/golgi --> binds *EF-2*

(TEST): A 14-year-old boy presented to the emergency department in August with a recent onset of sore throat, runny nose, headache, vomiting, stiff neck, mental confusion and lethargy that rapidly proceeded to coma. His health had previously been excellent, and the only significant history that could be elicited from the family was that he had been swimming in a shallow, stagnant lake near his home with friends a few days earlier. During the diagnostic evaluation, the cerebrospinal fluid was found to be turbid with decreased glucose, elevated protein, and leukocytosis, but Gram stain and culture for bacteria were negative. Despite aggressive clinical management, the patient expired. Which of the following organisms is the most likely cause of this illness?

*Naegleria fowleri* - *young children, males* - rapidly fatal meningoencephalitis = "brain-eating parasite" = Primary Amebic Meningoencephalitis (PAM) - swimming in freshwater lakes (think *Nalgene* bottle filled with *fresh water* containing *Naegleria* - amoebas in spinal fluid - enters cribriform plate - Amphotericin B has been effective for few survivors

(TEST): Infection with this organism, acquired during fresh water swimming that often involves diving or jumping into the lake, causes a primary amebic encephalitis which is invariably fatal.

*Naegleria fowleri* - 95% of patients die within 1 week - history of swimming week earlier

(TEST): A 14-year-old boy presented to the Emergency Department in the middle of summer with a recent onset of sore throat, runny nose, headache, vomiting, stiff neck, mental confusion and lethargy that rapidly proceeded to coma. His health had previously been excellent, and the only significant history that could be elicited from the family was that he had been swimming in a shallow, stagnant lake near his home with friends a few days earlier. During the diagnostic evaluation, the cerebrospinal fluid was found to be turbid with decreased glucose, elevated protein, and leukocytosis, but Gram stain and culture for bacteria were negative. Despite aggressive clinical management, the patient expired. Which of the following organisms is the most likely cause of this illness?

*Naegleria fowleri* = free living amoeba - Primary Amebic Meningoencephalitis (PAM), primary amoebic meningoencephalitis - acquired by exposure to amoeba in freshwater - trophozoites penetrate *cribiform palte* --> follow olfactory nerves into brain - rapidly fatal (3-7 days), usually diagnosed after death - acute inflammation & hemorrhagic necrosis in stage 2 - CSF = high neutrophil count, low glucose, high protein - treatment = *Miltefosine* + Amphotericin B + Rifampin + Fluconazole + Azithromycin + Dexamethasone

A colony of Neisseria gonorrhoeae is isolated on Thayer-Martin medium. All cells in this colony produce the same antigenic type of pilus. Inidivulal cells from this colony are exposed to lysate from a different strain of N. gonorrhoeae that produces a different pilus type. After overnight growth on plates, the bcaterial colonies are individually analyzed for pilus expression. In 50% of the new colonies, a new antigenic form of pilus is now expressed. What genetic event is most likely the explanation for this phenomenon?

*Natural transformation* - when lysates of bacteria are added to viable cells, DNA can be taken up by living cells by process of transformation only a few medically important species undergo natural transformation: - Haemophilus species - Streptococcus species - Neisseria species - Heliocbacter pylori - These organisms are capable of taking up free DNA without pretreatment In N. gonorrhoeae, it is estimated that up to a million antigenically distinct types of pili can be formed by RecA dependent recombination between expressed pilE gene & silent or storage genes (pilS)

(TEST): Heavy infection with this organism can cause a microcytic & hypochromic iron deficient anemia, especially in small children.

*Necator americanus* - via nematode (roundworm) - intestinal infection causing anemia by sucking blood form intestinal wall - *cutaneous larve migrans* - pruritic, serpiginous rash from walking barefoot on contaminated beach - transmission = larvae penetrate skin - treatment = bendazoles or pyrantel pamoate

(TEST): Acquisition of what organism from an infected mother during birth can result in a fast developing (1-3 days) perinatal conjunctivitis?

*Neisseria gonorrheoae* - can be transmitted from pregnant woman to her child during delivery = *ophthalmia neonatorum* - occurs on first or second day of life - can damage cornea = blindness - bc neonatal Chlamydia eye infections are also a threat, *erythromycin* eye drops, which are effective against *both* Neisseria gonorrhoeae & Chlamydia, are given to newborns

(TEST): This sexually transmitted organism is a significant cause of urethral discharge in infected men and can cause an acute, purulent, rapidly developing conjunctivitis in neonates if transmitted during birth by an infected mother.

*Neisseria gonorrhoeae* - causes gonorrhea, septic arthritis, neonatal conjunctivitis, pelvic inflammatory disease (PID), & Fitz-Hugh-Curtis syndrome - treatment = ceftriaxone + (azithromycin or doxycycline) for possible chlamydial coinfection

Indole test differentiates...

*Neisseria meningitidis (N. lactamica in lab) from Haemophilus influenza* Neisseria menin. - cocci, indole negative - glu/malt/suc positive Haemophilus influenza - pleomorphic, indole positive - XV required

Discharge due to mucopurulent cervicitis may be caused by

*Neisseria* or *Chlamydia*

Cleaves sialic acid residues on cell surface & increases binding sites for cholera toxin

*Neuraminidases* - modified cell surface --> increased GM1 binding site for cholera toxin

Important in protecting lungs from A.baumannii

*Neutrophils* A. baumannii = problematic for neutrophilic febrile patients - possible implications for clinical management

A biology graduate student who recently visited a tropical region of Africa presents with new visual impairment & the sensation that something is moving in her eye. She tells you that she is concerned bc she had been warned about eye disease transmitted by black flies. When in Africa, she was in a river area, & despite her best efforts she received a lot of black fly bites. She also has some subcutaneous nodules. If her infection was acquired by black fly bite, what is the most likely causative agent?

*Onchocerca volvulus* - filarial infection in Africa & Central & South America - microfilariae (larvae) mature into adults --> can be found coiled up in fibrous nodules in skin & subcutaneous tissue - after mating = microfilariae = pruritic skin rash with darkened pigmentation - microfilariae may migrate to eye --> blindness - treatment = ivermectin

(TEST): 2 most common infectious causes of blindness in the world

*Onchocerca volvulus, Chlamydia trachomatis* Onchocerca volvulus - larvae transmitted to humans by bite of infected black flies - pruritic skin rash with darkened pigmentation - lizard skin - microfilariae may migrate into eye --> river blindness - microfilariae can often be seen in eye (cornea & anterior chamber) by slit lamp examination - treatment = ivermectin

A florist presents with a subcutaneous lesion on the hand, which she thinks resulted from a jab wound she received while she was making a sphagnum moss-wire for a floral wreath. The nodule has ulcerated & not healed despite use of antibacterial cream, & a new nodule is forming above the original lesion. What is the most likely to be an appropriate treatment for this infection?

*Oral itraconazole or potassium* - K+ iodide administered orally in milk *Lyphocutaneous sporotrichosis* via Sporothrix schenckii - gardener or florist infected via puncture wound = cigar-shaped to oval yeasts - dimorphic fungi in soil & plants (rose thorns, splinters) - subcutaneous nodule gradually appears --> necrotic & ulcerates --> heals --> new nodules pop up nearby & along lymphatic tracts up arm - yeast reproduce by building - 37 C = yeast - 25 C = branching hyphae (dimorphism) treatment: - itraconazole, fluconazole, oral potassium iodide

Caused by B. Bacilliformis

*Oroya fever* - human reservoir - endemic to *Peru* - endemic in high valleys of Andes (Peru, Equador, Columbia) - disease mostly among non-natives - probable vector = sandfly - anemia + bacillary angiomatosis skin lesions = varuga peruana - varuga = wart - peruana = peruvian - non-encapsulated - via *sandfly in Andes* - *Oroya Fever* = bacillary angiomatosis (in immunocompromised) & anemia - treatment = *erythromycin (macrolides) &/or doxycycline*

(TEST): Which class of antibiotic blocks the formation of the 70 S ribosome?

*Oxyzolidinones*

(TEST): A 27-year-old female presents to the emergency room with complaints of left flank pain, fevers and chills. She noted increased urinary frequency and foul-smelling urine on the day prior to admission. She presented with a temperature of 39.8º C and physical examination showed left costovertebral angle tenderness. Urinalysis of a clean-catch urine sample was notable for >40 white blood cells, 4 to 10 red blood cells and 4+ bacteria per highpower field. Urine culture was positive for >100,000 CFU of a lactose-positive gram-negative rod. What virulence factors of Escherichia coli is most likely responsible for bacteria adhesion to uroepithelial cells in this patient's case?

*P pili* - Acquisition of a pili virulence factor allows E. coli to travel up the urethra & infect the bladder (cystitis) & sometimes move further up to infect the kidney itself (pyelonephritis) - E. coli = most common cause of UTIs, which usualy occur in women & hospitalized patients with catheters in urethra - symptoms = burning on urination (dysuria), having to pee frequently (frequency), & feeling of fullness over bladder - culture of greater than 100,000 colonies of bacteria from urine = diagnosis of UTI

Leading cause of nosocomial pneumonia

*P. aeruginosa* Treatment: *CAMPFIRE* *C*arbapenems *A*minoglycosides *M*onobactams *P*olymyxins *F*luoroquinolones Th*IR*d- & fourth-generation cephalosporins Extened-spectrum penicillins

Leading cause of contact lens-associated corneal infections (keratitis)

*P. aeruginosa* - hypopeon = collection of WBCs in anterior chamber - half-moon shape because of gravity

A 26-year-old woman with uncomplicated malaria who was treated initially with chloroquine now has relapse. What is the reason for a chloroquine-treated case of Plamodiuum vivax relapsing?

*P. vivax has a persistent exoerythrocytic stage (hypnozoite)* - both plasmodium ovale & plasmodium vivax have resting liver form = very slow to develop into schizonts with merozoites & proceed into chloroquine-sensitive erythrocyctic stages after treatment is over

(TEST): Infection with this organism, acquired in the United States by eating raw or poorly cooked crayfish, is characterized by fever, hemoptysis, dyspnea, and chest pain.

*Paragonimus kellicotti* / North American lung fluke - food-borne trematode infection - humans eat raw or undercooked crayfish meat that contains parasite larvae - common in Sub-Saharan Africa - after parasite has been ingested, it travels from intestines until it reaches lungs

Associated disease: Chlamydophila psittaci

*Parrot fever, ornithosis*, also in sheep, cows, goats

(TEST): Treatment for Weil's Syndrome, severe disseminated disease with multi-organ involvement (Leptospira interrogans infection)

*Penicillin*

Treatment of Syphilis

*Penicillin* - no resistant Treponema has even been found Tetracyclin or Erythromycin - for patients allergic to penicillin - should not be given to pregnant women Jarisch-Herxheimer rxn - flu-like symptoms due to mass killing of T.p. by antibiotic (releases lipoproteins)

How is Leishmania donovani transmitted?

*Sandfly bite* Leischmani donovani - visceral leishmaniasis (kala-azar) = spiking fever, hepatosplenomegaly - cutaneous leishmaniasis - skin ulcers - macrophages containing amastigotes - treatment = amphotericin B, sodium stibogluconate

(TEST): A mother brings her 4-year-old child to your office and tells you that lately the child has been irritable, has had trouble sleeping, and suffers from nightmares. While you are discussing the case you notice the child is scratching his behind. Which of the following diagnostic test would be most likely to identify the cause of this child's symptoms?

*Perianal scotch tape prep* Enterobius vermicularis / Pinworm - treatment = albendazole, mebendazole, pyrantel pamoate, avoid scratching, change sheets daily

Most prevalent vaccine-preventable disease in developed countries

*Pertussis* via Bordetella pertussis - vaccine immunity does wane over time though - current vaccine may need to be improved - gram negative, aerobic coccobacillus - virulence factors = pertussis toxin (disables Gi) & tracheal cytotoxin - causes whoopeing cough - prevented by *Tdap* & *DTaP* vaccines - may be mistaken as viral infection due to lymphocytic infiltrate resulting from immune response

(TEST): Which of the following lists of parasites can be transmitted from mother to neonate either transplacentally in utero or during birth?

*Plasmodiuim falciparum, Treponema pallidum, Trypanosoma cruzi* Plasmodium falciparum - most common & deadly - continuous episodes of fever & chills

(TEST): What organism causes a periodic progression of chills, fever, & sweats recurring 48 hours after onset?

*Plasmodium vivax* Plasmodium vivax/ovale - 48-hr cycle (tertian; includes fever on first day & third day, thus fevers are actually 48 hours apart) - dormant form (hypnozoite) in liver - transmission = Anopheles mosquito - blood smear: trophozoite ring form within RBC, schizont containing merozoites; red granules (Schuffner stippling) throughout RBC cytoplasm seen with P vivax/ovale - treatment = chloroquine (for sensitive species) --> blocks Plasmodium heme polymerase - if resistant, use mefloquine or atovaquone/proguanile - if life-threatening, use intravenous quinidine or artesunate - for P vivax/ovale, add primaquine for hypnozoite

(TEST): Although this organism remains the most common opportunistic infection in AIDS patients in the U.S., the introduction of highly active anti-retroviral therapy (HAART) has decreased its occurrence. It causes an interstitial plasma cell pneumonia in immunosuppressed individuals for which trimethoprim-sulfamethoxazole (TMP-SMX) is the treatment of choice in the absence of contraindications. Adjunctive corticosteroid therapy may be required to treat severe pneumonia in HIV-infected individuals, and long-term chemoprophylaxis is recommended in HIV patients with CD4 counts <200. The organism that matches this description is

*Pneumocystis jiroveci* - causes pneumocystis pneumonia (PCP) = diffuse interstitial pneumonia - yeast-like fungus - inhaled - most infections are asymptomatic - immunosuppression (AIDS) predisposes to disease - diffuse, bilateral ground-glass opacities on CXR/CT - diagnosed by lung biopsy or lavage - disc-shaped yeast seen on methenamine silver stain of lung tissue - treatment/prophylaxis = TMP-SMX, pentamidine, dapsone (prophylaxis only), atovaquone - start prophylaxs when CD4+ count drops to <200 cells/mm^3 in HIV patients

(TEST): Although this organism remains the most common opportunistic infection in AIDS patients in the U.S., the introduction of highly active anti-retroviral therapy (HAART) has decreased its occurrence. It causes an interstitial plasma cell pneumonia in immunosuppressed individuals for which trimethoprim-sulfamethoxazole (TMP-SMX) is the treatment of choice. Adjunctive corticosteroid therapy may be required to treat this severe pneumonia in HIV-infected individuals, and long-term chemoprophylaxis is recommended in HIV patients with CD4 counts <200 per μL. The organism that matches this description is

*Pneumocystis jirovecii* = fungus in lungs of mammals without overt infection until host's immune system becomes debilitated --> lethal pneumonia - thickened alveolar walls & alveoli filled with "foamy" eosinophilic exudate - abnormal chest films: symmetrical cloudiness bilaterally with honeycomb pattern via lobular collapse & emphysema - treatment = TMP-SMX

A male newborn delivered at 30 weeks' gestation develops respiratory distress. A chest x-ray shows diffuse bilateral infiltrates. Further exam of lower respiratory tract secretions obtained on transmural needle biopsy shows roughly spherical bodies with sharply outlined walls when stained with methenamine silver. What is the most likely causal organism?

*Pneumocystis jirovecii* = opportunistic infection in premature infants & patients with AIDS - chest x-ray = diffuse bilateral infiltrates - CT scan = patchy areas of ground-glass opacity = alveolar spaces & interstitial thickenings - visualized by silver stain - causes atypical pneumonia via over-replication of type 2 pneumocytes & their production of surfactant-rich exudates --> fill alveolar sacs --> death by asphyxiation - officially classified as fungal pneumonia but does not respond to antifungal treatment - treatment = trimethoprim-sulfamethoxazole (TMP-SMX) --> usage in newborns should be closely monitored due to risk of kernicterus (excessive jaundice)

(TEST): Which one of the following forms of infection with Yersinia pestis can be transmitted human to human?

*Pneumonic plague* Yersinia pestis - During epidemics, disease can also be seen as pneumonic plague with pneumonia & human-to-human transmission by aerosolized bacteria

(TEST): Which one of the following offers the highest sensitivity and specificity for diagnosing an infection with Neisseria meningitidis?

*Polymerase chain reaction of central spinal fluid*

Occurs in 10-20% of patients with Lyme disease patients get antibiotic treatment. *Lingering symptoms* of fatigue, pain, cognitive defects, sleep disturbance, joint & muscle aches.

*Post-treatment Lyme Disease Syndrome (PTLDS) - Chronic Lyme?* - spirochetes not found in affected tissue - patients usually improve with time but symptoms can *last up to 6 months* Other stages... Stage 1 = early localized = erythema migrans, flu-like symptoms Stage 2 = early disseminated: secondary lesions, carditis, AV block, facial nerve (Bell) palsy, migratory myalgias/transient arthritis Stage 3 = late disseminated: encephalopathies, chronic arthritis

(TEST): Treatment for infections with Taenia tapeworms

*Praqziquantel*

(TEST): Used in the treatment of Plasmodium vivax malaria in order to eliminate the dormant liver hypnozoite stages of organism

*Primaquine phosphate* Plasmodium vivax - 48 hour intervals/tertian form = vivax & ovale - continual reproduction in liver (hypnozoites, latern liver stage) - anemia - chloroquine sensitivity - mosquitos & sporozoites - infects RBCs --> lysis - local tissue anoxia - insoluble hamazoin form Hb breakdown in phago in liver & sleen - organs enlarge; kidney becomes plugged - rupture of spleen - *Tertian malaria* = fever, chills, anemia, splenomegaly, relapses possible - release via HYPNOZOITES in liver can re-infect RBCs

(TEST): There are three stages of disease during pertussis. What stage of pertussis = patients MOST likely to spread disease to others

*Primary stage* - book says Catarrhal stage is most contagious

(TEST) often associated with UTIs due to biofilm formation on urinary catheter

*Proteus* - urea-splitting - exam of urine = alkaline pH via Proteus' ability to split urea into NH3 & CO2

Primary cause of death in 80% of CF patients

*Pseudomonas Biofilms* - downregulate flagella genes once they come towards surface

(TEST) Organism that can secrete multiple proteases & is always resistant to ampicillin & first generation cephalosporins

*Pseudomonas* Do NOT expect P. aeruginosa to be susceptible to PAS FF - penicillin - ampicillin - amoxicillin - first generation cephalosporins - sulfa-trimethoprim - furantoin

(TEST): You have a patient with gastrointestinal illness caused by Vibrio parahaemolyticus. Which of the following foods was the most likely source of the Vibrio?

*Raw oysters* V. parahaemolyticus - shellfish/seawater; GE, bacteremia; thermostable direct hemolysin

A 48-year-old subsistence farmer from rural Brazile dies of heart failure. His autopsy shows a greatly enlarged heart. What was the vector for the most likely infectious agent that may have been responsible for his death?

*Reduviid bug* = Chagas's disease --> caused by Trypanosoma cruzi - defecate as they bite - (acute) fever, edema, myocarditis; (chronic) cardiomyopathy, conduction defects, megacolon, megaesophagus - acute = blood smear; chronic = serology, PCR - treatment = *benznidazole*

(TEST): Which one of the following represents an appropriate treatment for Whooping Cough in the paroxysmal stage?

*Respiratory support including oxygen* - treatment primarily supporive - infants hospitalized to provide oxygen, suctioning of respiratory secretions, respiratory isolation, & observation - treatment of infected individuals with erythromycin in prodromal or catarrhal stage may prevent disease - later therapy during paroxysmal stage does not alter course of illness by may decrease bacterial shedding

(TEST): In zygomycosis which one of the following is the most likely potentially fatal disease form that would be seen?

*Rhinocerebral* - most common - germinates directly into brain Zygomycota - irregular, broad, nonseptate hyphae branching at wide angles - mucomycosis - causes disease mostly in *ketoacidotic patients* &/or neutropenic patients (leukemia) - fungi proliferate in blood vessel walls, penetrate cribriform plate, & enter brain - *rhinocerebral*, frontal lobe abscess - cavernous sinus thrombosis - treatment = *amphotericin B*

Disease caused by R. akari

*Rickettsialpox* - vector = *mites* - reservoir = rodents, mites = febrile illness, eschar, rash - diagnosis = serology, PCR - treatment = *doxy*, quinolones = mild, self-limited, febrile disease that starts with initial localized red skin bump (papule) at the site of the mite bite -- turns into blister (vesicle) --> days later = fever & headache develop; other vesicles appear over body - eliminate nearby rodents

(TEST): Infection with this flea-borne organism causes high fever, intense headaches and a characteristic petechial rash that spreads centrifugally from the trunk toward the extremities.

*Rickettsie typhi* = Endemic or Murine Typhus - via rat flea, Xanopsylla cheopis - treatment = doxycycline or chloramphenicol

(TEST): Often used with another antibiotic to prevent emergence of resistant sub-population

*Rifamycin* - Mycobacterium tuberculosis, Haemophilus influenza type B Rifampin - N. meningitidis prophylaxis: along with MCV4 & B vaccine - Brucella: doxycycline + rifampin

Most Serratia infections due to what species?

*S. marcescens* - some due to S. liquefaciens & S. odorifera Serratia... - slow lactose-fermenting Enterobacteriaceae - gram-negative, oxidase-negative, glucose-fermenting rod - produces salmon red pigment

Strict human pathogens and can cause asymptomatic long-term colonization ("Typhoid Mary")

*S. typhi* --> typhoid fever, febrile illness *S. paratyphi* - S. paratyphi, S. schottmuelleri, S. hirschfeldii --> parathyroid fever = less severe form = asymptomatic colonization - 1-5% of patients harbor it in gallbladder & can shed it in feces - most infections are from ingesting contaminated food, commonly poultry, eggs, dairy - direct fecal-oral spread in children - especially in warmer weather months

Highest incidence of trachoma is where?

*Sahel belt of Africa & East Africa* Chlamydia trachomatis serotypes A, B, C = *A*frica, *B*lindness, *C*hronic infection

(TEST): A Peace Corps volunteer who had recently returned from Africa presented with fever, abdominal pain, and urticaria. Physical and laboratory examination revealed an enlarged liver and spleen, non-operculate ova with a prominent lateral spine in the stool, and a significant eosinophilia. Further history revealed that the patient and several other Peace Corps colleagues had gone swimming in a local river near the village where they worked shortly before returning to the U.S. The patient says that one of these colleagues also is experiencing similar symptoms and has a neurological deficit of the lower extremities. What is the most likely cause of this illness?

*Schistosoma mansoni* - via trematodes (flukes) - liver & spleen enlargement = egg with lateral spine - fibrosis & inflammation - snails are host - cercariae penetrate skin of humans - treatment = praziquantel = South America & Africa - resides in intestinal tract - deposits eggs in feces - found in freshwater - practice molecular mimicry = tricks host's immune system into thinking schistosome are *not* foreign

Syphilis Diagnosis

*Serological* tests based on 2 types of treponemal Abs *Non-treponemal specific Ab* (screening) - rapid plasma reagin (*RPR*) & Venereal Disease Research Lab (*VDRL*) - syphilis = cellular damage --> release into serum of lipids, including *cardiolipin* & lecithin - body produces Abs against Ags --> measure titer - 1% of adults without syphilis also have these Abs = false positive = pregnancy, infectious mononucleosis, viral hepatitis *Treponema specific Abs* (confirmatory) - reacts with Treponema pallidum - fluoresecent Treponemal Ab (*FTA-ABS*) & T. pallidum Hemagglutination (*TPHA*) - Abs against spirochete itself Microscopic - spirochetes in lesion - dark field or fluorescent microscopy PCR detection of bacterial DNA

Diagnosis of Leptospirosis

*Serology, ELISA (via CDC)* *PCR* *Culture (septicemic stage)* Leptospira interrogans - spirochete in *water contaminated with animal urine* - flu-like symptoms, myalgias (calves), jaundice, photophobia with conjunctival suffusion (erythema without exudate) - prevalent among *surfers in Hawaii / tropics* - Weill disease / icterohemorrhagic leptospirosis = severe form = severe form with jaundice & azotemia from liver & kidney dysfunction, fever, hemorrhage, anemia

Contact lens induced acute red eye (CLARE) due to

*Serratia* = member of Enterobacteriaceae (Coliforms) = hospital-acquired neonatal infections, such as meningitis, CNS abscesses, sepsis - community-acquired necrotizing fasciitis - UTIs - pneumonia

EHEC produces

*Shiga toxin (Stx-1, Stx-2, or both)* - Stx-1 = identical to Shigella dysenteriae toxin - Stx-2 = 60% homologous - both toxins acquired by bacteriophages - both are A-B toxins (1 A & 5B) - cause A/E lesions on epithelial cells - have large plasmid that carries other virulence genes - inhibit protein synthesis by inhibiting 60S ribosome = intestinal epithelial cell death

(TEST): Hemolytic uremic syndrome (HUS) is mediated via what bacterial virulence factor?

*Shiga toxin*

(TEST): A 28-year-old male who just returned from a vacation in a developing country presents with severe abdominal cramps and low-volume stools containing blood and pus. Initial laboratory diagnosis with the triple sugar iron (TSI) agar slant determines that the infecting organism preferentially utilizes glucose, then converts to utilization of amino acids when the glucose is exhausted due to lack of a lactose operon. No hydrogen sulfide is produced. The likely cause of this patient's gastrointestinal illness is

*Shigella flexneri* - nonmotile - no flagella - does not ferment lactose - does not produce H2S

A 3-year-old boy who attends a large daycare facility suddenly develops fever, vomiting, diarrhea, & abdominal pain. While in the emergency department three days later, he has more than 10 bowel movements, each containing mucus, blood, & pus. He has developed weight loss & severe dehydration. His temperature is 38 C (100.4 F), blood pressure is 90/60 mmHg, pulse is 130/min, & respirations are 20/min. O2 saturation is 98%. No rashes are observed. What is the most likely causal agent?

*Shigella sonnei* = Shigellosis/Bacillary dysentery - acute infection of bowel that can be caused by variety of Shigella species, including S. flexneri, S. sonnei (most common isolate in United States), S. boydii, S. dysenteriae - Only S. sydenteriae produces Shiga toxin = assocaited with hemolytic-uremic syndrome - spread among humans via fecal-oral route via contaminated food or inanimate objects - humans = only natural host for Shigella species - epidemic commonly occur in crowded populations with poor sanitation - mini-epidemic have occurred in daycare setting - TMP-SMX may shorten duration

(TEST): Type of medium used for identification of Escherichia coli O157:H7 cultures

*Sorbitol/MacConkey agar* E. coli Diagnosis - grows rapidly on MacConkey - many O157 strains *do not ferment sorbitol* = sorbitol-containing MacConkey agar used as screening tool - EIEC difficult to distinguish because large virulence plasmid can get lost in vitro

Rickettsia infection - tick vectors - *centripetal rash* = extremities --> trunk

*Spotted fever group* - R. rickettsi = RMSF = most severe - R. parkeri = spotted fever with escar - R. akari = rickettsialpox

How is Schistosoma haematobium transmitted?

*Standing or swimming in contaminated water* - skin penetration via cervariae - snails = intermediate host Schistosoma = egg with terminal spine - can lead to squamous cell carcinoma of bladder (painless hematuria) & pulmonary hypertension - treatment = praziquantel

Most commonly bacteremia & pneumonia in immunocompromised patients previously exposed to broad-spectrum antibiotics.

*Stenotrophomonas maltophilia* - like Burkholderia, was previously part of genus Pseudomonas - high incidence of complications & death - *resistant* to multiple antibiotics, including *carbapenems* - treatment = sulfa-trimethoprim - aerobic, nonfermentative, Gram-negative bacteria - motile due to polar flagella - grow well on MacConkey agar producing pigmented colonies - catalase-positive, oxidase-negative - ubiquitous in aqueous environments, soil, & plants - can lead to nosocomial infections

A 38-year-old man presented with a 5-day history of productive cough, headache, and fever. He complained of mouth and throat soreness and painful lip lesions. His medical history was unremarkable. Also... - conjunctivitis - swollen, crusted lips, pseudomembranous lesions in the oropharynx - despite antimicrobial therapy with clarithromycin (250 mg twice a day), his condition worsened - new target lesions on scrotal skin as well as - *erosive lesions* on anal mucosa & glans penis evolved 48 hours after admission - lung auscultation = bilateral whistling rales detected - chest radiograph demonstrated prominent peribronchial cuffing - bronchoscopy showed extensive ulcerative endobronchial lesions & purulent bronchitis - PCR from bronchoalveolar lavage fluid was positive for documented 10 days later

*Steven-Johnson Syndrome* - Mycoplasma pneumoniae infection complicated by *severe mucocutaneous lesions* - treatment = corticosteroids (topical), antibiotics, pain medication, antihistamines - characterized by fever, bullae formation & necrosis, sloughing of skin at dermal-epidermal junction, high mortality rate - typically 2 mucous membranes involves - targetoid skin lesions may appear, as seen in erythema multiforme - usually associated with adverse drug reaction - more severe form with >30% of body surface area involved in toxic epidermal necrolysis

Typical pneumonia caused by

*Streptococcus pneumonia* *Haemophilus influenza* *Staphylococcus aureus* Gram-negative bacillus (Klebsiella pneumoniae) Viruses

(TEST): The presence of live larvae with a short buccal chamber in the stool of a patient suffering from epigastric pain, diarrhea, vomiting, and urticarial skin eruptions, is diagnostic for infection with

*Strongyloides stercoralis* / Threadworm - intestinal infection causing vomiting, diarrhea, epigastric pain (may mimic peptic ulcer) - transmission = larvae in soil penetrate skin - treatment = ivermectin or bendazoles

(TEST): Most common presentation of chronic Q fever (Coxiella burnetii infection)

*Subacute endocarditis* Q fever: Acute - high fever, pneumonia Chronic - endocarditis

A 16-year-old man who recently returned from camping in Canada presents with fatty diarrhea & acute abdominal pain following many meals. How does the most likely agent cause the diarrhea?

*Suction disk attachment* - Giardia lamblia = causative agent - carried by muskrats & beavers = northern lakes, like Canada - attachment of numerous Giardia via ventral sucking disks in duodenal-jejunal area --> malabsorption diarrhea & temporary lactose intolerance

Clinical algorithms based on STI syndrome to determine presumptive antimicrobial therapy

*Syndromic management*

(TEST): A drug formulation that inhibits peptide bond formation and causes the release from the ribosome-mRNA complex of the growing polypeptide is

*Synercid* = quinupristin/dalfopristin - treats infections by staphylocicci & by vancomycin-resistant Enterococcus faecium - streptogramin antibiotics

(TEST): Primary prophylaxis for opportunistic infections with Pneumocystis jirovecci and/or Toxoplasma gondii in HIV positive patients with CD4+ counts less than 200/mm3

*TMP-SMX (trimethoprim-sulfamethoxazole)*

Tapeworm acquired from eating undercooked pork

*Taenia solium* - pork tapeworm attaches to mucosa of intestine via hooks on its scolex - grows to length of 2-8 meters - releases its eggs in human feces - in animal's muscle tissue, larvae develop into another larval form, the cysticercus = round, fluid-filled bladder with larval form within - elevated eosinophils intestinal tapeworm - via ingestion of larvae encysted in undercooked port - treatment = praziquantel cystericosis, neurocysticercosis - via ingestion of eggs contaminated with human feces - treatment = praziquantel, albendazole for neurocysticercosis

(TEST): A 29-year-old male who recently arrived from Mexico is brought to the UMC emergency room after suffering a seizure while working in the hot sun with a highway construction crew. On examination, he appeared to be healthy and his physical findings were all normal. Tests for infectious agents including stool ova and parasites were negative. The seizure responded to anti-convulsive therapy and he was released. Two weeks later he returned to the hospital after suffering another seizure. A CT scan showed two intraparenchymal ring-enhanced lesions measuring 8 mm by 1.5 cm and scattered punctuate calcifications. The results of serologic tests showed a strongly positive titer to antigens from which organism?

*Taenia solium* / Pork Tapeworm - humans via ingestion of undercooked pork infected with larvae Cysticerci in brain = Neurocysticercosis - 7-10 cysts in brain --> seizures, obstructive hydrocephalus, focal neurologic deficits - cysts grow slowly --> 5-10 yrs later = begin to die & leak fluid contents - endemic areas = Mexico, Center & South America, Philippines, SE Asia = most common cause of seizures there - Diagnosis via CAT scan or biopsy of infected tissue (brain or muscle) - treatment = albendazole or praziquantel - elevation of eosinophil level in blood

Treatment for Relapsing Fever

*Tetracycline*, Erythromycin - LBRF - single dose - TBRF - daily doses for 10 days - Erythromycin/Penicillin for children, pregnant women - Ceftriaxone (10-14 days) if neurologic involvement - *Doxycycline or Erythromycin* = treatment of choice - monitor patients for Jarish-Herxheimer reaction (50%) = rigors & hypotension Borrelia recurrentis --> Relapsing Fever - via body louse (Pediculus humanus) - likes to feed on sleeping campers in western US, especially those who sleep in rodent-infested, rustic mountain cabins - rapidly changing surface proteins = Abs no longer recognize them - antigenic variation --> continued relapses for weeks - Wright's or Giemsa-stained smear of peripheral blood during febrile periods = spirochete between RBCs

(TEST): When Legionella pneumophila enters a macrophage, it is able to avoid the lysosomal network and subsequently lyse the macrophage releasing bacteria that can spread to other cells. L. pneumophila is able to do this due to

*The DOT/ICM system* Legionella Virulence - DOT/ICM = defect for organelle trafficking / intracellular multiplication system - Type IV secretion system - secretes proteins into cytoplasm of phagocyte (>275 substrates) - Legionella containing vacuole (LCV) - avoids fusion with endocytic vesicles & lysosomes - acquired endoplasmic reticulum markers - replicates, macrophage lysis, can spread to other cells

(TEST): In a triple sugar iron (TSI) agar slant, what is the interpretation if the top portion of the slant has turned red following inoculation with bacteria and incubation at 37 °C for 24 hours?

*The bacteria are using amino acids as carbon source in this section of the slant*

(TEST): Acinetobacter baumannii has become multiply drug resistant in a relatively short period of time. Which one of the following occurrences contributed most significantly to this development?

*The bacterium has acquired a large resistance island*

(TEST): Which of the following describes an appropriate treatment for Neisseria gonorrhoeae?

*The gonorrhea treatment now favored includes a third generation cephlosporin & azithromycin*

(TEST): What best describes an appropriate treatment for Neisseria gonorrhoeae?

*The gonorrhea treatment now favored includes third generation cephalosporin & azithromycin* 3rd generation cephalosporins - enhanced activity against gram-negative organisms - high potency against H. influenza, N. gonorrhoeae, N. meningitides, Enterobacter, Salmonella, indole-positive Proteus, & Serratia, & E. coli - moderate activity against anaerobes - Ceftriaxone used for sexually transmitted infections caused by gonorrhea, as well as in empiric therapy for community-acquired meningitis

Virulence factor of V. parahaemolyticus

*Thermostable direct hemolysin / Kanagawa hemolysin* V parahaemolyticus & V vulnificus via contaminated seafood Vibrio parahaemolyticus - marine bacterium that causes gastroenteritis after ingestion of uncooked seafood (sushi) = leading cause of diarrhea in Japan

(TEST): Pseudomonas aeruginosa can often be successfully treated with

*Timentin & Tobramycin* Tobramycin - Enterobacter, indole-positive Proteus, Pseudomonas, Klebsiella, Serratia Timentin = Ticarcillin/Clavulanic acid *CAMPFIRE* *C*arbapenems *A*minoglycosides *M*onobactams *P*olymyxins (polymyxin B, colistin) *F*luoroquinolones (ciprofloxacin, levofloxacin) Th*IR*d- & fourth-generation cephalosporins (ceftazidime, cefepime) *E*xtended-spectrum penicillins (piperacillin, ticarcillin)

(TEST): Resistance to what antibiotic is mediated by acetylation or adenylation of the drug?

*Tobramycin* - P. aeruginosa treatment (ticarcillin + Tobramycin), piperacillin + tobramycin, ceftazidime + tobramycin, timentin + tobramycin = aminoglycoside = broad spectrum IV thearpy, often with a beta-lactam Aminoglycosides - *resistance caused by >100 enzymes that modify antibiotic (phosphorylation, acetylation, adenylation; aph, aac, ant genes, respectively), also mutation in ribosomal binding site* - requires oxygen for uptake, *not effective for strict anaerobes* - toxic concentrations easily reached --> impacts hearing & kidney function - irreversible binding = misreading of mRNA & faulty proteins & premature termination - bactericidal

Diseases caused by Chlamydia trachomatis, serotypes A, B, Ba, C

*Trachoma (eye infection)* - contact with eye secretions, also spreads by flies - reservoir = humans *ABC* = *A*frica, *B*lindness, *C*hronic infection

Caused by Bartonella Quintana

*Trench Fever* - human reservoir - vector = body louse = 5 days illness = recurrent fever - conditions of poor sanitation/hygiene - *not* an obligate intracellular organism* - quintana = characteristic 5-day interval between febrile episodes

Common causes of Vaginal discharge

*Trichomonas vaginalis / bacterial vaginosis*

Protozoan transmitted primarily by motile trophozoite form

*Trichomonas vaginalis* (& Giardia lamblia) - wet mount - treatment = metronidazole

Associated with *Colpitis Macularis ("strawberry cervix")*

*Trichomoniasis vaginalis* - NOT - lower abdominal pain, dysuria, vulval edema - foul-smelling, greenish discharge - itching & burning - sexual = trophozoites (motile) on wet mount - treatment = metronidazole for patient & partner (prophylaxis)

(TEST): Organisms that can all cause dysenteric (bloody) diarrhea

*Trichuris trichiura, Plasmodium falciparum, Entamoeba histolytic* Trichuris trichiura - simple slow life cycle - ingestion of contaminated food with eggs --> eggs hatch in GI tract --> migrate to cecum & ascending large intestine = abdominal pain & diarrhea Entamoeba histolytic - sometimes the trophozoites invade the intestinal mucosa = erosions = abdominal pain, couple of loose stools a day, flecks of blood & mucus in stool - infection may become severe = bloody, voluminous diarrhea Plasmodium falciparum = most aggressive form of malaria

Rickettsia infections: - flea or louse vectors - *centrifugal rash* = trunk --> extremities

*Typhus group* - R. typhi (fleas) - endemic or murine typhus - R. prowazekii (lice) - epidemic typhus

(TEST): Which of the following gram-negative rods would be the most likely cause of a wound infection after exposure of a skin cut to seawater?

*Vibrio vulnificus* - raw oysters, contaminated shellfish, wound infections & swimming in ocean (along with V. parahaemolyticus) - virulence factors = antiphagocytic polysaccharide capsule, cytolysins, collagenase, protease, siderophores - capsule important for full virulence of species (disseminated infections) = bacteremia, wound infection, cellulitis - V. vulnificus wound infections & septicemia treatment = minocycline + fluoroquinolone or cefotaxime

(TEST): Most common arthropod-born viral encephalopathy in MS

*West Nile fever* - flavivirus spread by mosquitos - endemic in US

(TEST): When does an Escerichia coli cell have the highest cyclic AMP concentration?

*When growing on amino acids*

Factor requirements of H. ducreyi (genitalia)

*X* H. ducreyi - chancroid - painful genital ulcer with exudate, inguinal adenopathy

Factor requirements for H. aegyptius (oropharynx)

*X, V + CO2* = most fastidious Haemophilus influenza biogroup aegyptius - purulent conjunctivitus / pink eye

Nonvenereal Treponemal Infection: Diseases of children

*Yaws & Bejel* - young adults = Pinta - Pinta = tropical areas of S. & C. America - Bejel = desert/temperate regions of N. Africa & Middle East - Yaws = warm humid tropical areas of Africa, Asia, South & Central America, & Oceania - skin ulcers & gummas of skin & bones in children - morphologically & genetically identical to Treponema pallidum - Abs produced by these infections = positive VDRL & FTA-ABS - treatment = one intramuscular infection of long-acting penicillin

Warm humid tropical areas of Africa, Asia, South & Central America, & Oceania. Initial lesion if papule that becomes *large papilloma*. Secondary disease produces *multiple cutaneous lesions* with *regional lymphadenopathy*. Tertiary stage produces *bone, joint, & tissue deformities*

*Yaws* - chronic disfigurin & debilitating childhood infectious disease caused by Treponema pallidum subspecies pertenue - cured by single oral dose of azithromycin = most common of the endemic treponematoses

(TEST): A 47-year-old male who works on a timber farm had two courses of antibiotic treatment for right lower lobe pneumonia. He felt better, but developed an ulcerative lesion on his left forearm. A center punch biopsy revealed numerous granulomatous cells but no microorganisms were seen microscopically. A second biopsy from the periphery of the lesion was performed. Which of the following would likely describe the microorganisms seen?

*a broad budding yeast*

(TEST): A 47-year-old male who works on a timber farm had two courses of antibiotic treatment for right lower lobe pneumonia. He felt better but developed an ulcerative lesion on his left forearm. A center punch biopsy revealed numerous granulomatous cells, but no microorganisms were seen microscopically. A second biopsy from the periphery of the lesion was performed. Which of the following would likely describe the microorganisms seen?

*a broad budding yeast* Blastomycoses

(TEST): A 22-year-old male college student, upon returning to school from New Orleans for spring break, developed septicemia. He reported that he became sick with diarrhea after eating a dozen raw oysters. The bacteremia resolved after treatment with minocycline and cefotaxime, which the patient's physician chose to use after laboratory identification of the bacterial species causing the septicemia. The laboratory was able to identify the causative organism- a small, curved rod- by virtue of its growth on

*a high salt medium such as thiosulfate citrate bile salts sucrome medium* V. Vulnificus - raw oysters, contaminated shellfish, wound infections, swimmin ocean - septicemia after consumption of contaminated raw oysters, especially in middle of summer - treatment for V. vulnificus wound infections & septicemia = minocycline + fluoroquinolone or cefotaxime

(TEST): The original vaccine for whooping cough was composed of formalin-fixed intact bacterial cells. The current vaccine is best described as being

*acellular vaccine* Vaccine - required by law in US - historically = heat-killed phase I cells - current vaccine is acellular - immunity is not life-long - DTaP given in 5 doses for children - ages 2 months, 4 months, 6 months, 15-18 months, 4-6 years - booster recommended at 11-12 years of age Diphtheria toxoid Tetanus toxoid P - whole killed phase I bacterial cells aP - pertussis toxoid, adhesin proteins - acellular pertussis DTaP & Tdap = acellular formulations

Treatment for HSV-1 (oral) & HSV-2 (genital)

*acyclovir*, val, fam, reduce severity/duration

E. coli UTIs *tend* to be caused by specific serogroups that possess

*adhesins* - optimized for attachment to cells lining the bladder & upper urinary tract (P pili, type I fimbriae, Dr) *hemolysis HlyA* - can lyse host cells & stimulate inflammation Use fimbriae to attach tightly to cells of urinary tract --> E. coli internalized --> replicated --> inflammatory cytokine production --> inflammatory cells fight off infection --> sloughing --> high quantities of E. coli, macrophages

What happens to TSI Agar Slant if bacteria can ferment lactose or sucrose

*agar stays yellow (E. coli)* - butt is anaerobic = glucose here can only be fermented = acid = yellow (E. coli) - *produces CO2 gas (air pockets in bottom)* - has lactose operon --> uses lactose after 12 hours when glucose is exhausted (slant stays yellow)

Grow Legionella pneumophila on

*charcoal yeast extract agar* (L-cysteine = critical ingredient) - gram-negative bacilli - aerobic - non-spore forming - non-encapsulated = facultative intracellular parasite that settles in lower respiratory tract & is gobbled up by macrophages; in free living amoebas - inhibits phagosome-lysosome fusion - can enter low metabolic state & can survive in biofilm Treatment - macrolides, tetracycines, quinolones = atypical coverage (Mycoplasma, Legionella, Chlamydia)

Proteus treatment: catheterized patients that are seriously ill require two-drug regimen:

*ampicillin* with either *monobactam aztreonam (azactam), second or third-generation cephalosporin, gentamicin* or another *aminoglycoside* or *ciprofloxacin*, or other *fluoroquinolones* - monobactams: aztreonam = gram-negative rods only; for penicillin-allergic patients & those with renal insufficiency who cannot tolerate aminoglycosides - 2nd generation cephalosporins = cefaclor, cefoxitin, cefuroxime = proteus miribalis - 3rd generation cephalosporins = ceftriaxone, cefotaxime, ceftazidime = serious gram negative infections resistant to other beta-lactams - aminoglycosides: gentamicin = severe gram negative rod infections - fluroquinolone: ciprofloxacin = gram negative rods of urinary & GI tract

(TEST): A characteristic sign of infection with Borrelia burgdorferi (Lyme disease) is

*an expanding bull's-eye rash* Early Localized Stage - 10 days after tick bite --> lasts 4 weeks - skin lesion at site of tick bite (erythema chronicum migrans) along with flulike illness & regional lymphadenopathy - ECM starts off as red (erythematous) flat round rash --> spreads out (migrates) over time (chronicum)

(TEST): The most common means of transmission of gram-negative zoonotic bacteria, especially in young children

*animal bites*

(TEST): A patient who had been in excellent health developed hemorrhagic pneumonia and MRSA was identified as the causative organism. The patient was placed on intravenous synercid. This therapy was likely

*appropriate & sufficient* Synercid: Quinupristin/Dalfopristin - combo of two streptogramins = binds 50S ribosome in different sites - can be bacteriostatic or bactericidal - narrow spectrum: MRSA - IV only - inhibits CYP3A4

(TEST): During an infection, bacteria susceptible to gentamicin can survive treatment with this antibiotic provided they

*are intracellular*

(TEST): Common manifestations of early disseminated Lyme disease include

*arthritis & multiple erythema migrans* Early Disseminated Stage - dissemination of Borrelia burgdorferi spirochetes to 4 organ systems - ECM - multiple lesions on body, smaller - migratory joint & muscle pain - 6 months after infection, attacks of arthritis can occur - large joints, such as knee, become hot, swollen, & painful - neurologic - transient heart block or myocarditis

Treatment for Chancroid caused by Haemophilus ducreyi

*azith*, ceft, cip, eryth

Treatment for Donovanosis, granuloma inguinale

*azith*, doxy, eryth, tet, TMP/SMX

Treatment for chlamydia

*azithromycin* (favored because one-time treatment), doxy, eryth

Treatment of Chancroid - Haemophilus ducreyi

*azithromycin* or ceftriaxone or alternative ciprofloxain or erythromycin - large ulcers may take weeks to resolve

Morganella diseases

*bacteremia in hospital patients* *UTIs* *wound infections in hospital patients* Morganella morganii - gram-negative - facultatively anaerobic - oxidase-negative - colonies = off-white & opaque - straight rods - moves via peritrichous flagella - produces catalase - indole-positive

(TEST): A neutropenic patient presents with severe sinusitis which has failed to respond to antibiotics. A CT of the head revealed sinus thickening. A biopsy was performed and fungal elements were observed in the specimen. This case should

*be considered a medical emergency, requiring emergency surgery, antifungal therapy, & reversal of the neutropenia if possible* FUNGAL SINUSITIS - *should be considered in all patients with chronic sinusitis* - noninvasive form: fail to respond to repeated courses of antibiotics - invasive form: occurs in immunocompromised patients; associated with malignancies, *neutropenias*, diabetes *Invasive* Fungal Sinusitis - *emergency surgery* to remove necrotic & devitalized tissue - treatment with *amphotericin B* should be initiated based on microscopic staining of tissue - *reverse immunosuppression* (discontinue corticosteroids, treat iatrogenic neutropenia) Aspergillosis - immunocompromised/neutropenic host - invasive sinusitis, pulmonary disease, dissemination - CAN BE LIFE THREATENING Fusarium - difficult to differentiate from Aspergillus - treatment = AMB, voriconazole or posaconazole - sinusitis: must reverse neutropenia

Morganella has resistance to

*beta-lactams* - resistant to: penicillin, ampicillin/sulbactam, oxacillin, first- & second-gen cephalosporins, macrolides, lincosamide, fosfomycin, colistin, polymyxin B Morganella morganii - gram-negative - commensal relationship with intestinal tract - facultatively anaerobic & oxidase-negative = off-white & opaque on agar plates - straight rods - peritrichous flagella - treatment = ticarcillin, piperacillin, ciprofloxacin, 3rd & 4th gen cephalosporins

(TEST): The pathogenesis of infection with Mycoplasma pneumoniae results from

*binding to ciliated respiratory epithelium causing ciliostasis* Mycoplasma pneumoniae - attaches to respiratory epithelial cells with help of protein P1 (an adhesin virulence factor)

(TEST): Erythromycin has a bacteriostatic effect on susceptible bacteria that is mediated by

*blocking translocation of ribosome to allow another tRNA to bind* Erythromycin = Macrolide (ACE) - inhibits protein synthesis by *blocking translocation* (macro*slides*) - binds to 23S rRNA of 50S ribosomal subunit - bacteriostatic Clinical use - aypical pneumonias (mycoplasma, chlamydia, legionella), STIs (chlamydia), gram positive cocci, B pertussis

Important for full virulence of V. vulnificus

*capsule production* - disseminated infections - V. vulnificus more deadly in terms of sepsis

Treatment for Gonorrhea

*ceft + azith/doxy* cefix *ceft or eryth ointment for infant conj.*

Pasteurella associated with what disease?

*cellulitis* Pasteurella multicida - gram-negative zoonotic organism - colonizes the mouths of cats = wound infection following cat or dog bite - don't close the wound with sutures after a bite! - treatment = penicillin or doxycycline

In females, the primary site of Gonorrhea is

*cervix*, endocervical columnar epithelial cells - vaginal discharge, dysuria, abdominal pain, vaginal bleeding

(TEST): Aspergillosis would most likely occur in people with

*compromised immune system* Aspergillus flavus / Aspergillosis - Allergic Broncho-Pulmonary Aspergillosis (ABPA) - Aspergilloma - Invasive Aspergillosis - *Immunocomprised hosts can develop invasive pneumonias & disseminated disease* - bloody sputum may occur via blood vessel wall invasion via Aspergillus hyphae Invasive aspergillosis - usually occurs in immunocompromised hosts such as patients who are neutropenic after chemotherapy or patients on high dose steroids for treatment of graft vs. host disease - patients with end-stage AID & CD4 counts less than 50 cells/microL Treatment - voriconazol, amphotericin preparations, caspofungin

ETEC usually acquired through

*consumption of fecally contaminated water or food* ETEC... - 80,000 cases per year in US travelers = *traveler's diarrhea (watery)* - main virulence factors = colonization factor antigens (CFA) / adhesins, heat-stable toxins (ST), & heat-labile (LT) enterotoxins - usually no inflammation or histological changes to mucosa - infant diarrhea in developing countries - monomeric toxin binds guanylyl cyclase --> GTP --> cGMP --> secretion of chloride via CFTR

(TEST): Human infection with Leptospira interrogans (leptospirosis) is typically acquired by

*contact with rodent urine*

(TEST): Human infection with Leptospira interrogans (leptospirosis) is typically acquired by

*contact with rodent urine* - leptospira in urine of dogs, rats, livestock, wild animals - spirochetes can penetrate abraded skin or mucous membranes when humans come in contact with urine either directly or by swimming in contaminated water (swallowed)

Prominent characteristic/virulence factor of Klebsiella

*copious, mucoid capsule* - common isolates = K. pneumoniae & K. oxytoca (community-acquired primary lobar pneumonia) - alcoholics & people with compromised pulmonary function = at higher risk Also... - NDM-1: metallo-beta-lactamase-1 = resistance to broad range of beta lactams - endemic in Vietnam - Donovan bodies = small rods in PMNs - via Giemsa stain - granulomatous lesions: genitals & groin areas

(TEST): An intravenous drug user presents with symptoms consistent with meningitis. Microscopic examination of a specimen from a lumbar puncture reveals the presence of encapsulated, oval budding yeast. To help confirm your diagnosis, you should order a

*cryptococcal antigen test* Cryptococcocis neoformans - *encapsulated oval, budding yeast* - occurs widely in nature - associated with *pigeon droppings* - infection via inhalation - high salt & polysaccharides (bird droppings) limits capsule formation - regenerates capsules once in lungs = lung infection, predilection for CSF, meningitis - one of the most common life-threatening infections in AIDS patients Diagnosis: - lumbar puncture - demonstrate presence of encapsulated yeast - latex agglutination test - antigen assay

(TEST): An intravenous drug user presents with symptoms consistent with meningitis. Microscopic examination of a specimen from a lumbar puncture reveals the presence of encapsulated, oval budding yeast. To help confirm your diagnosis, you should order a

*cryptococcal antigen test* Cryptococcus neoformans = *major cause of meningitis in patients with AIDS* = 5-10 um with narrow budding - heavily encapsulated yeast - not dimorphic - found in soil, pigeon droppings - acquired via inhalation with hematogenous dissemination to meninges - culture on Sabouraud agar - highlighted with India ink & mucicarmine (red inner capsule) - latex agglutination test detects polysaccharide capsular antigen & is more specific - causes cryptococcosis, cryptococcal meningitis, cryptococcal encephalitis (soap bubble lesions in brain), primarily in immunocompromised

(TEST): The Burkholderia cepacia complex (BCC) contains organisms which are dangerous for patients who have

*cystic fibrosis* Burkholderia cepacia - presence contraindicated for lung transplant patients - treatment = trimethoprim-sulfamethoxazole

(TEST): Infection limited to the lower urinary tract (bladder) is called

*cystitis* UTI/Acute Bacterial Cystitis: causes - E. coli (most common) - Staphylococcus saphrocyticus - Klebsiella - Proteus mirabilis

(TEST): A recent opportunistic outbreak of fungal central nervous system infections was caused by contaminated glucocorticoid injections from a compounding pharmacy. These infections are usually associated with the

*dematiaceous molds* Phaeohyphomycoses = infections caused by *dematiaceous* / black molds containing melanin in their cell walls - typically associated with allergic fungal sinusitis, brain abscess, &, in rare outbreaks associated with *contaminated steroid solutions prepared by a compounding pharmacy*, meningitis = *OPPORTUNISTIC* - treatment = surgical drainage or excision - *Amphotericin B* for epidural or brain abscesses - *Itraconazole* longterm for sinusitis - *Voriconazole* for meningitis

Citrobacter treatment

*double* antibiotic regimen of *pencillin* or *3rd generation cephalosporin plus aminoglycoside* *chloramphenicol* has good penetration into abscesses & is sometimes used Citrobacter koseri - brain abscesses in neonates - transmitted nosocomially or vertically (mother --> fetus) - gram-negative coliform bacteria in Enterobacteriaceae fam - can use citrate as a sole carbon source - differentiated by their ability to convert tryptophan to indole - ferment lactose - use malonate

Treatment of RMSF

*doxy*, chlor = treatment for all rickettsial diseases - febrile illness, headache, rash (centripetal), vasculitis (organs/digits) - diagnosis = serology, PCR RMSF - via rickettsia rickettsii - presents within week after person is bitten by either wood tick Dermacentor andersoni or dog tick Dermacentor variabilis - rash that appears on wrists, ankles, soles, & palms --> later spreads to trunk - more common in Southeastern US - organism proliferates in endothelial lining of small blood vessels & capillaries = small hemorrhages & thrombi

Treatment for Lymphogranuloma venereum (LGV)

*doxy*, eryth

(TEST): The treatment for acute Q fever (Coxiella burnetii infection) is

*doxycycline*

(TEST): The four possible mechanisms of virulence of Pseudomonas aeruginosa in the human host are: biofilm formation (as seen in cystic fibrosis), cytotoxic action on host cells via an injected lipase, secretion of exolysin to lethally attack the surface of the host cells, and

*invasion of cells by injecting proteins that mediate uptake of bacteria* Exoenzymes S, T, Y - invasion of P. aeruginosa into host cells - injected by Type III secretion system - trigger engulfment of bacteria ExoS & ExoT - host actin rearrangement for bacterial engulfment ExoU - lipase activity --> quickly kills ccells ExoY - adenylate cyclase --> increased cAMP --> disrupts cell shape --> nonserine lactose production

EIEC: characterized by...

*invasion* & destruction of colonic epithelium - pathogenic strains associated with serotypes O124, O143, O164 - rare in US & uncommon in developing countries - dysentery = fever, abdominal cramps, blood & pus in stool - large plasmid carries genes for invasion into epithelial cells (invasion plasmid antigens, or ipa) - bacteria become internalized with phagocyte-like vacuole --> escape into cytoplasm --> replicate --> spread to adjacent cells via host actin tails

(TEST): A patient presents with severe sinusitis which has failed to respond to multiple rounds of antibiotics. The patient has profound prolonged neutropenia and is in the pre-engraftment phase of hematopoietic cell transplantation (allogeneic). The most likely diagnosis in this patient is

*invasive sinusitis*

(TEST): A patient presents with severe sinusitis which has failed to respond to multiple rounds of antibiotics. The patient has profound prolonged neutropenia and is in the pre-engraftment phase of allogeneic hematopoietic cell transplantation. The most likely diagnosis in this patient is

*invasive sinusitis* - occurs in immunocompromised patients - associated with malignancies, *neutropenia*, diabetes

(TEST): A patient presents with severe sinusitis which has failed to respond to antibiotics. The patient has recently received a kidney transplant and is on immunosuppressive medication. The most likely diagnosis in this patient is

*invasive sinusitis* - occurs in immunocompromised patients - associated with malignancies, neutropenia, diabetes

(TEST): Infections caused by Pseudomonas aeruginosa are particularly worrisome because the organism

*is frequently resistant to multiple classes of antibiotics*

(TEST): Two distinguishing characteristics of the family Enterobacteriaceae, which includes E. coli and Shigella species, are glucose fermentation and

*lack of oxidase activity*

2 primary genes of Las

*lasR & lasl* Las R - transcriptional activator triggered by environmental cues - mutated in CF lung patients = hyperinflammatory response LasR + 3-oxo-C12-HSL (PAI-1) targets lasl (& rhlR) - 3-oxo-C12-HSL (PAI-1) = homoserine lactone (HSL) autoinducer 'cule produced during quorum sensing - PAI-1 available to bind LasR via production from nearby bacteria - Las I = autoinduction loop within bacterial cell by producing more PAI-1 --> can bind & activate LasR (autoinducer loop) & can signal neighboring bacteria

A former resident of Indianapolis living in Seattle, WA presents with symptoms characteristic of a pulmonary fungal infection. He has resided in the Seattle area for the past 20 years and has not traveled outside of the state. He is HIV positive and has had a declining CD4 cell count. A sputum sample is positive for Histoplasma capsulatum. His infection is

*likely due to reactivation of disease* Histoplasmosis - bat, chicken, bird droppings - dimorphic: mycelial in env' - yeast at 37 - occurs via respiratory tract - reactivation in old foci of infection can occur via immunosuppression --> reduced cellular immunity - 80% of ppl in Ohio Valley have evidence of infection by age 18 - phagolysosome fusion = raises pH to 5.5-6.5

Principal clinical symptoms of secondary syphilis

*macropapular rash, condylomata lata* - 6 weeks after primary chancre has healed - bacteria multiply & spread via blood throughout body - systemic with widespread rash, generalized lymphadenopathy, involvement of many organs - condyloma latum = painless, wartlike lesion in warm, moist sites like the vulva or scrotum = packed with spirochetes, ulcerates = contagious! - skin infection in areas of hair growth = patchy bald spots & loss of eyebrows

(TEST): Neiseeria meningitidis has several virulence factors associated with the outer membrane. An additional mechanism of virulence develops from

*membrane blebbing*

(TEST): The drug treatment of choice for infection with Trichomonas vaginalis, and for treatment of bacterial vaginosis, an alteration of normal vaginal flora, is

*metronidazole*

Treatment for Trichomoniasis

*metronidazole* tinidazole Trichomoniasis - vaginitis, strawberry cervix, motile in weat prep

V. vulnificus treatment: wound infections & septicemia

*minocycline plus fluoroquinolone or cefotaxime* - fluoroquinolones = gram negative rods of urinary & GI tract - cefotaxime = 3rd generation cephalosporin = serious gram negative infections - tetracyclines = both gram - & gram + organisms. rickettsial infections, cholera, lyme disease, chlamydia, mycoplasma pneumonia. inflammatory acne vulgaris. h. pylori.

(TEST): Infections with Cryptosporidium parvum and Cyclospora cayatenensis, which both cause an acute watery diarrhea, are diagnosed by

*modified acid fast stain of a stool specimen* Intestinal cryptosporidiosis = acute watery diarrhea of short duration (1-2 weeks) with abdominal pain & cramps, dehydration, nausea, vomiting, fever, weight loss - profuse diarrhea in immunocompromised patients - diagnosis = stool exam for oocysts; modified acid fast staining; DIC; DFA; Ag immunoassays - treatment = Nitazocanide Cyclospora cayetanensis - *unsporulated occysts* pass in human feces = 2-4 um larger than Cryptosporidium oocysts - contain Acid Fast morula (blob of cells) - become infective after week of sporulation - related to Isospora - should be considered in differential diagnosis of prolonged diarrhea, especially in patients with history of travel - oocysts must be measured to differentiate from Cryptosporidium - treatment = TMP-SMX - transmitted via fecal-oral route - has been implicated in food borne outbreaks of diarrhea associated with contaminated rasberries - diagnosed by stool microscopy

Two patients in a burn unit develop signs of infection (e.g., pus) at the site of their burns and a spiking fever. A culture shows lactose-negative colonies on MacConkey agar and the TSI medium has an alkaline slant but no growth in the but. The patients had been treated with a first generation cephalosporin and gentamicin, but based on the culture findings, the therapy is changed to ceftazidime (a third generation cephalosporin) and tobramycin. This therapy is

*proper & sufficient* P. aeruginosa treatment = antibiotic combo therapy of beta-lactam & aminoglycoside - Ticercillin + Tobramycin - Piperacillin + Tobramycin - Ceftazidime + Tobramycin - Cefepime + Amikacin - Timentin + Tobramycin Fluoroquinolone therapy (can be oral) - Ciprofloxacin - Levofloxacin - Moxifloxacin or Gatifloxacin

(TEST): The production of Pseudomonas aeruginosa biofilm in the cystic fibrosis lung is dependent on

*quorum sensing*

(TEST): A former resident of Mississippi living in the Miami, FL presents with symptoms characteristic of acute pulmonary fungal infection. He has resided in the Miami area for the past 20 years and has not traveled outside of the state. He is HIV positive and has had a declining CD4 cell count. A sputum sample is positive for Histoplasma capsulatum. His infection is likely due to

*reactivation disease* Histoplasma capsulatum - CD4+ cell count <100/mm^3 - fever, weight loss, fatigue, cough, dyspnea, nausea, vomiting, diarrhea - oval yeast cells within macrophags

(TEST): In zygomycosis, what is the most likely disease form that would be seen?

*rhinocerebral* Zygomycosis - broadest test to refer to infections caused by bread mold fungi - infections found in soil & decaying vegetation Rhinocerebral mucomycosis - rare opportunistic infection of sinuses, nasal passages, oral cavity, & brain - can rapidly result in death affects individuals with diabetes & in immunocompromised states

(TEST): MacConkey agar is best described as

*selective & differential medium* MacConkey agar - bile salts in medium inhibit gram-positive bacteria - lactose fermenters develop pink-purple coloration

(TEST): The primary diagnostic technique for obligate intracellular bacteria from the genera Rickettsia, Orientia, Coxiella, Ehrlichia, and Anaplasma is

*serology for antibody in paired sera specimens* Orientia tsutsugamushi / Scrub Typhus - arthropod born - small aerobic - obligate intracellular - *chiggers (larval stage of mites)* - dev in bv epithelium & macrophages - treatment = doxycycline, chloramphenicol

(TEST): Rocky Mountain spotted fever is diagnosed by the presence of characteristic clinical features (fever, centripetal rash), patient history of tick bite, and

*serology for antibody* Rickettsia Rickettsii - arthropod born - small aerobic - obligate intracellular - poor gram staining - dermacentor tick vectors - develop in endothelial cells - treatment = doxycycline, chloramphenicol *Lab diagnosis = serology, PCR; Weil-Felix agglutination test*

(TEST): The initial diagnosis of ornithosis (Chlamydophila psitacci infection) relies on patient history and clinical signs, but definitive diagnosis of infection requires

*serology of acute & convalescent sera* diagnosis - history of exposure to birds & clinical signs - serology (IgG/IgM), 4-fold increase in paired samples - direct immunofluorescence staining (DFA) - CF cross-reacts with C. pneumoniae, C. trachomatis - PCR (experimental) - tissue culture (research labs only) treatment - doxycycline (tetracycline) - erythromycine

(TEST): Non-venereal treponemal infections are typically transmitted by

*skin contact* - treatment = penicillin G (IM); oral doxycycline, tetracycline, erythromycin - spirochete

(TEST): Non-venereal treponemal infections (Pinta, Yaws, Bejel) are typically transmitted by

*skin contact* Treponema pallidum Subspecies - skin ulcers & gummas of skin & bones in children

Serological classification of Enterobacteriaceae is based on 3 major groups of antigens:

*somatic O polysaccharides* - specific to genus *capsular K antigen* - type-specific polysaccharides *flagellar H proteins* K & H antigens are under genetic control = can be alternately expressed or not expressed (phase variation) - protects bacteria from Ab-mediated cell death

(TEST): A 35-year-old female seeks medical attention for a rash on the palms and soles of her feet. The result of her rapid plasma reagin test is 1:128. The most likely diagnosis is

*syphilis* - secondary syphilis: rash = small red macular (flat) lesions symmetrically distributed over body, particularly involving the palsm soles, & mucous membranes of the oral cavity

(TEST): Appropriate antibiotic therapy for patient with H. pylori would be

*tetracycline* H. pylori treatment: Antibiotics (1-2 weeks) - *Tetracycline*, metronidazole, & omeprazole Bismuth salts (Pepto-Bismol) Tetracycline... - active against both gram-negative & gram-positive organisms = predominately used for rickettsial infections, cholera, Lyme disease, infections caused by Chlamydia & Mycoplasma pneumonia - may be used for inflammatory acne vulgaris - used in combo regiments for elimination of infections caused by Helicobacter pylori

Describe resistance of P. aeruginosa to Disinfectants

- alginate in biofilms on abiotic surfaces = shield - modification of porins --> prevents penetration of disinfectants - efflux pumps can remove toxic chemical - resistance to triclosan, chlorhexidine, & benzalkonium chloride (ophthalmic formulations)

Proteus treatment: for infection in blood & endocarditis

*third generation cephalosporin plus gentamicin or cipro alone* - also: tigecyline + amikacin Gentamicin (Garamycin) - active against Enterobacter, *indole-positive proteus*, pseudomonas, klebsiella, serratia, among other gram-negative organisms - often used synergistically in combo with beta-lactam antibiotics or vancomycin in serious infections that require broad coverage Amikacin - used for severe, gram-negative infections, especially those resistant to gentamicin or tobramycin

(TEST): A patient presents with a single, circular lesion with a prominent red edge and central clearing located on his right shoulder. This dermatophytic infection is clinically described as

*tinea corporis* (body) - follows invasion of horny layer of skin --> fungi spread --> form ring shape with red, raised border - expanding raised red border = active inflammation with healing center = ring-worm Dermatophytoses = cutaneous fungal infections - live in dead, horny layer of skin, hair, & nails - fungi secrete keratinase enzyme --> digests keratin = scaling of skin, loss of hair, crumbling of nails - common dermatophytes = Microsporum, Trichophyton, Epidermophyton

An organism isolated from a patient's urine sample was show to be lactose fermenting on TSI media. A cherry red color appeared upon addition of Kovac's reagent. This reagent tests for the ability of organism to cleave

*tryptophan, yielding indole* - some bacteria convert AA tryptophan into chemical indole - indole can be detected specifically in media by use of Kovac's Reagent --> reacts almost immediately with indole to produce red color - indole not present = produces brownish color

Principal clinical symptoms of primary Syphilis

*ulcerated indurated lesion (some nongenital), bilateral nonsupperative inguinal adenopathy* - localized disease presenting with *painless* chancre - use dark-field microscopy to visualize treponemes in fluid from chancre - VDRL positive in 80% - very infectious (chancre)

(TEST): A female patient complained to her physician of a pain in the lower abdomen and self-diagnosed a urinary tract infection. A clean catch sample of her urine grew out approximately 100 colonies per ml of an indole-positive gram-negative rod-shaped organism. Her physician should conclude that she should

*undergo additional tests to find the cause of her pain*

(TEST): A 45-year-old male has a history of smoking two packs of cigarettes a day. He works for an open-water pond servicing company. He presents with complaints of shortness of breath and 'flu-like symptoms that have been present for about a week. Cultures of lung sputum fail to grow anything on blood agar. Based on this history, which one of the following laboratory tests would likely be the most informative?

*urine antigen test* - can be detected by radioimmunoassay with high sensitivity & specificity & will remain positive for months after infection - only detects L. pneumophila serogroup 1, but this accounts for 90% of cases Legionella - ubiquitous in natural & man-made water environments - Pontiac fever = flulike illness - misdiagnosis - not able to culture organism or infection with one not detected by urine antigen test

Human Papillomavirus Infection Treatment

*wart removal* (cryosurgery, topical medications such as podofilox, excision, acids, CO2 laser) *vaccines now available* - Gardasil (Merck Co.) protects against HPV types 6, 11, 16, & 18 (90% of warts) - Cervarix (GlaxoSmithKline) protects against HPV 16 & 18 (75% of cervical cancer)

Treatment for HPV

*wart removal* - surgery *podofilox*, cryosurgery - podofilox = topical treatment of external genital warts (condyloma acuminatum)

Aeromonas associated with what disease

*wound infection* - exposure to contaminate water Aeromonas - gram-negative, facultatively anaerobic, rod-shaped - ubiquitous in fresh & brackish water - gastroenteritis & wound infections - most severe = necrotizing fasciitis

(TEST): The Vibrio cholerae virulence factor that is responsible for loosening the tight junctions of the small intestinal mucosa, thus increasing intestinal permeability, is

*zonnula occludens toxin*

Lyme Disease Diagnosis

- *Erythema migrans* = pathognomonic - history of tick exposure - serology - difficult to do culture - patient presents with ECM? --> leading edge of rash biopsied --> cultured - levels of anti-Borrelia burgdorferi antibodies - ELISA - Western immunoblotting Treatment: Doxycycline, Penicillin

Late Congenital Syphilis (>age 2) characteristics

- *Hutchinson's triad* (63%) = tooth deformation (H's teeth), Interstitial keratitis (eyes), 8th nerve deafness - *Saddle nose* (74%) - *Bone deformations* (Saber Shins)

Virulence factors of Mycoplasma pneumoniae

- *P1 adhesion protein* on attachment organelle binds sialic-rich glycoproteins in *respiratory epithelium* - *community-acquired respiratory distress syndrome toxin* (CARDS), ADP-ribosyltransferase with vacuolating & pro-inflammatory activity

Chlamydophila pneumoniae treatment

- *azithromycin*, clarithromycin - alternatives: doxycycline, tetracycline - erythromycin for children, pregnant women Chlamydophila pneumoniae - cause of community acquired pneumonia - upper respiratory tract symptoms - rhonchi & rales - immunoflorescence or CF, PCR, tissue culture

Clinical forms of Cat Scratch Disease (CSD)

- *bacillary angiomatosis* in AIDS = proliferative vascular lesion resembling Kaposi's sarcoma - subacute endocarditis (culture negative) - retinitis - via Bartonella henselae

Drug resistance problems of Klebsiella

- *constitutive beta-lactamases* --> resistance to amoxicillin, ampicillin, ticarcillin - ESBL/extended spectrum beta-lactamase producing strains = resistant to ceftazidime & aztreonam = treated with carbapenems - carbapenemase-producing klebsiella (KPC) have *broad resistance but may be susceptible to tigecycline or colistin* - strains producing *metallo-beta-lactamase, including NDM-1* = resistant to almost everything --> may be treated with tigecycline or colistin

Primary Syphilis Characteristics

- *hard chancre* = 2-8 weeks at site of infecton - *painless indurated ulcer* = may be overlooked in women - teeming with spirochetes - *very infectious* - some regional lymphadenopathy (*buboes*) - heals spontaneously without treatment - Abs made but organisms persist - *untreated about 50% progress to secondary syphilis* - regional nontender lymph node swelling - chancre resolves after 4-6 weeks without scar = fools infected individual into thinking infection has completely resolved

Males with symptomatic Gonorrhea

- *mucopurulent urethral discharge & dysuria* - 2-5 days incubation after sexual contact - infection primarily restricted to urethra - occasional epididymitis with scrotal/testicular pain - N. gonorrhoeae penetrates mucous membranes of urethra = inflammation of urethra (urethritis) - some men will remain asymptomatic, but most will complain of painful urination along with purulent urethral discharge (pus can be expressed from tip of penis) - epididymitis, prostatitis, & urethral strictures = potentially - disease easily cured by small dose of *ceftriaxone* - men having sex with men (MSM) = rectal gonococcal infection = only site of infection in this group = usually asymptomatic but can present with anal pruritis, tenesmus, &/or rectal bleeding & purulent discharge

Campylobacter Lab Diagnosis

- *no growth* on MacConkey agar (don't use carbs: glucose, fructose, sucrose) - growth *microaerophilically at 42 C* on Campylobacter selective agar

Tertiary Syphilis characteristics

- *prolonged latent period* (3-30 years) - can affect any tissue & be fatal - *gummas* - highly destructive granulomas, usually in skin & bones, also other tissues - *neuro-syphilis* - may resemble any neurological disease - *cardiovascular syphilis* - especially the aorta - lesions contain few spirochetes = exaggerated tissue responses due to hypersensitivity reactions

Secondary Syphilis characteristics

- *red maculopapular rash* anywhere on body including palms & soles - *white patches* on mucus membranes: *condylomata lata* on genital or anal areas - teeming with spirochetes & *very infectious* - heal spontaneously - relapses occur - *if untreated* - 1/3 spontaneously cured, 2/3 = latent - untreated patients enter this bacteremic stage 6 weeks after primary chancre has healed - bacteria multiple & spread throughout the body = systemic with widespread rash, generalized lymphadenopathy, & involvement of many organs - skin infection in areas of hair growth = patchy bald spots & loss of eyebrows - rash & condyloma lata resolve over 6 weeks --> disease enters latent phase

E. coli - TSI - Urea - Indole

- Acid over Acid - Negative Urea - Positive Indole (negative is brown) can both ferment & oxidize

Klebsiella: - TSI - Urea - Indole

- Acid over Acid & Gas - Negative Urea - Negative Indole

Treatment for Salmonella

- Antibiotics not recommended for enteritis - S. typhi, S. paratyphi, or disseminated infections with other organisms --> choose antiobiotic based on in vitro susceptibility testing = *fluoroquinolones, chloramphenicol, sulfa-trimethoprim, broad-spectrum cephalosporin* - prevent by proper food preparation - carriers of S. typhi & S. paratyphi should be identified & treated

Vaccine for N. meningitidis

- Based on capsular polysaccharide - Composed of *4 serogroups (groups A, C, Y, and W-135)* - Conjugate vaccine *(MCV4)* - Recommended for preadolescence or at risk young children *Serotype B vaccine*... - weekly antigenic - similar to glycoproteins of human neurons - composed of proteins that protect against 80% of type B isolates

Burkholderia Treatment

- CDC recommends determining on a case-by-case basis - often susceptible to *trimethoprim-sulfamethoxazole* - can be spread among CF patient, so important to try to prevent the spread - rapidly becoming an important pathogen, infecting hospitalized patients (burn & cystic fibrosis patients) in similar manner

Defining characteristics of Neisseria

- Cocci: pairs/diplococci with adjacent sides flattened - gram-negative - *aerobic* - *non-motile* - *oxidase positive*

E. coli Adhesins...

- Colonization factor antigens (CFA/I, CFA/II, CFA/III) - Aggregation adherence fimbriae (AAF/I, AAF/III) - Bundle-forming pili (Bfp) - Intimin - P pili - Ipa proteins (invasion plasmid antigens) - Dr fimbriae E. coli can remain in urinary or gastrointestinal tract by adhering to host cells & avoid being flushed away

Virulence of Legionella

- DOT/ICM = defect for organelle trafficking / intracellular multiplication system - Type IV secretion system - secretes proteins into cytoplasm of phagocyte (>275 substrates) - Legionella containing vacuole (LCV) - avoids fusion with endocytic vesicles & lysosomes - acquires endoplasmic reticulum markers - replicates, macrophage lysis, & can spread to other cells

Virulence factors of Plague

- Endotoxin - Exotoxin - Yops = found in supernatant of organism = part of type III secretion system = can deliver protein from cytoplasm of bacteria to host's cytoplasm Plague - caused by Yersinia pestis = non-motile, gram-negative rod with bipolar staining = appearance of safety pin - member of Enterobacteriacae fam = lactose fermenter - bipolarr staining pattern

Mechanism of pathogenesis of Shigella

- Shigella first attaches to M cells of Peyer's patches - Type III secretion system allows secretion of 4 invasion plasmid antigens (IpaA, IpaB, IpaC, IpaD) into epithelial cells & macrophages - Host membrane ruffling occurs --> bacteria engulfed within cell in phagocytic-like vacuole - bacteria lyse vacuole --> escape into cytoplasm --> replicate - bacteria (non-motile, no flagella) induce actin polymerization in host --> use actin tails to move within cell & adjacent cells - survive phagocytosis by residing intracellularly & by induced apoptosis of macrophages - release of IL-1beta attracts PMNs - intestinal wall becomes destabilized

Congenital Syphilis characteristics

- T. pallidum transmitted after *first trimester* (after fourth month of gestation) - 50% of fetuses *abort or stillborn* - remaining 50% = *diverse stigmata* - *early congenital syphilis*, up to age 2 = macropapular rash, hepatosplenomegaly, bone involvement, pneumonia, snuffles, testicular masses - *late congenital syphilis* = after age 2

Virulence factors of *Moraxella catarrhalis*

- adhesins - inactives complement - biofilm important in otitis media Moraxella catarrhalis - otitis media & upper respiratory infection in patients with COPD or emphysema or in the elderly - also cause pneumonia in the elderly - part of normal respiratory flora - gram-negative diplococci treatments - azithromycin or clarithromycin - amoxicillin with clavulanate - oral second or third gen. cephalosporin - trimethoprim/sulfamethoxazole

Characteristic of Elizabethikingia anophelis

- aerobic - gram-negative rod - soil, fresh-water, plants - hospital environment - all deaths associated with co-morbidity - almost all infections >65 y/o - isolated from gambiae mosquitos from Gambia

Proteus - TSI - Indole - Urea

- alkaline over acid; often H2S (stinks) - indole depends on species - ureas positive

Shigella treatment

- antibiotic therapy can shorten symptoms & prevent shedding in stool - empiric therapy = *fluoroquinolone, sulfa-trimethoprim, ampicillin* - susceptibility unknown or ampicillin- or sulfa-trimethoprim-resistant strain isolated = fluroquinolones, ceftriaxone, azithromycin - control = hygiene measures: handwashing, proper disposal of soiled linens Shigella... - don't ferment lactose - nonmotile (lack flagella/no H antigens) - don't produce H2S - have no animal reservoirs, only human hosts - invade M cells of intestine --> move into adjoining cells via actin polymerization (similar to Listeria) - produce shallow ulcerations usually without bloodstream invasion

Donovan bodies

- appearance of small rods in cytoplasms of histiocytes, PMNs, & plasma cells in *K. granulomatis* K. granylomatis... - gram-negative, rod-shaped bacterium - causes sexually transmitted disease granuloma inguinale / *donovanosis*

Diagnosis of Plague

- aspirates from buboes for staining - Giemsa's or Wayson's stain = better than Gram's stain - fluorescent-Ab staining of tissue - sputum can contain large # of bacteria - blood cultures are positive - diagnose quickly = can have as little as 24 hours

Characteristics of EPEC

- bacterial attachment to epithelial cells of small intestine - effacement (destruction) of microvillus (*attachment/effacement* [A/E]) - E. coli genes involved in A/E encoded on pathogenicity island - formation of bacterial microcolonies at attachment sites on host cell; on cup-like pedestals - produce bundle-forming pili & adhesin called intimin - affects mainly infants in developing countries - attachment to enterocytes in small intestines damages microvilli = malabsorption & diarrhea

P. aeruginosa has intrinsic resistance to

- beta-lactamases - mutation of porin genes = contributes resistance to disinfectants - mutations of genes normally targeted by fluoroquinolones (gyrA, gyrB, parC) - Efflux pumps

Recognize Klebsiella on Blood Agar & MacConkey Agar

- can utilize glucose & lactose --> look at center - Gram-negative - oxidase-negative - rod-shaped bacteria - prominent polysaccharide-based capsule = opportunists --> cause ventilator-associated pneumonias - found in human colon & in water

Result of plating Salmonella on TSI media

- can't use lactose or sucrose --> goes for amino acids = bright color change at top - whole bottom with turn black if incubated too long

Diagnosis of Nonvenereal Treponemal Infections (Yaws, Bejel, Pinta)

- clinical manifestations in geographical context - darkfield microscopy - serology - *VDRL or RPR (screening), FTA-ABS (confirmatory)* VDRL & FTA-ABS are positive

Diagnosis of Chlamydia trachomatis: LGV

- clinical signs (bubos) - Abs to Chlamydia LGV serogroups (L-1, L-2, L-3) - two samples, 4-fold rising titer - Ag detection - Polymerase chain reaction (PCR, NAATs) on voided urine - culture - special method for Chlamydia

Diagnosis of Neisseria meningitidis

- colonizes nasopharynx of healthy people - clinical specimens cultured on chocolate blood agar on *Thayer-Martin* agar: at 35-37 C in 5% CO2 - oxidase & catalase positive

Diseases caused by Haemophilus aegyptius

- conjunctivitis - Brazilian Purpuric Fever - purpuric skin rash & fever = clone has more virulence than rest of species maybe because it has plasmid

Chlamydia trachomatis Serotypes D to K cause

- conjunctivitis (of newborns & adults) - pneumonia in newborns - non-gonococcal urethritis (men & women) - proctitis (men & women) with rectal pain, discharge, bleeding - epididymitis in men - cervicitis, salpingitis, PID in women - *Fitz-Hugh-Curtis synrome* - peri-hepatitis: inflammation of serous covering of liver in 15-30% of PID cases - *Reiter's Syndrome* - reactive arthritis (joint swelling/pain) often with conjunctivitis & urethritis, also oral/genital & cutaneous lesions & nodular rash possible

How to diagnose Neisseria meningitidis

- culture from *sterile body fluid: CSF* = 90-90%, *blood* = 50%; *synovial or pleural fluid* - *skin biopsy* = 60% sensitivity - CSF *PCR* = 96% sensitivity; 100% specificity - antibiotics can sterilize CSF in <2 hours Meningococcal meningitis / Neisseria meningitidis... - gram-negative, oxidase-positive, kidney-shaped diplococcus with polysaccharide capsule - ability to use both glucose & maltose - gram-negative diplococci on Gram stain CSF - culture of CSF & blood on chocolate agar in high CO2 - do antibiotic susceptibility testing

Pertussis Diagnosis

- cultures from deep nasal swab: must contact ciliated epithelium - PCR detection - circulating Abs appear in 3 weeks Culture on Bordet-Gengou Agar or Regan-Lowe Agar - both supplemented with blood (sheep, horse) - beta-hemolytic, whitish-grey opalescent colonies - 4 days to colony formation (may take 7 days) - hemolysis may be less apparent

Function of outer-membrane vesicles (OMV)

- decoy - cell-cell signaling - toxin delivery - transfer of genetic material

Treatment for Brucella

- difficult because organisms are intracellular - prolonged treatment = 4-6 weeks - combo therapy = *doxycycline & rifampin*

Diagnosis of Tularemia

- difficult to culture - don't normally culture due to risk to lab personal - agglutination test - fluorescent-Ab staining of tissue can be used

Vibrio Lab Diagnosis

- difficult to see in stool or wound specimens - culture: specimens must be collected early in disease & inoculated promptly onto culture media - if culture has to be delayed, specimen should be mixed in *Cary-Blair* = agar with added salts in tube with swab - can grow on *blood or MacConkey agar* - selective agar for Vibrio = *thiosulfate citrate bile salts sucrose (TCBS)* = alkaline medium used to grow Vibrio cholerae - enrichment broth = alkaline peptone pH 8.6 - biochemical tests & serotyping

Describe the role of RhI system

- downstream of Las - activated LasR/PAI-1 --> transcription of rhlR --> encodes transcription factor RhlR = activated by quorum sensing signal 'cule *C4-HSL (PAI-2)* --> induces production of RhII --> produces more PAI-2 = positive feedback loop - promotes secreted virulence factors = responsible for *rhamnolipid* production

Nutrient requirements of Enterobacteriaceae

- facultative anaerobes - ferment glucose - reduce nitrate - catalase-positive

Mechanism of Salmonella

- ingested from contaminated food - invade & replicate in M cells (microfold cells) of Peyer's patches of small intestine - M cells: typically transport foreign antigens to underlying macrophages for clearance - bacteria bind to M cells with specialized fimbriae - initial invasion via type III secretion system encoded on Salmonella pathogenicitiy island 1 (SPI-1) - SPI-1 apparatus secretes invasion proteins (Sips or Ssps) into M cells = host membrane ruffling & engulfment of bacteria - bacteria replicate in phagosome-like compartments & spread to adjacent cells (are resistant to acidic pH via acid tolerance response [ATR] gene) - subsequent systemic disease occurs via type III secretion system encoded on Salmonella pathogenicity island 2 (SPI-2)

Source of Brucella infections

- ingestion of contaminated milk - direct contact with infected animal tissue - inhalation of bacteria

How one could be exposed to Legionella

- inhalation of aerosolized droplets - cooling towers - evaporative condensers - water sources that produce aerosols - grows on rubber & silicone (biofilms)

Presentation of Rickettsialpox

- initially an *eschar* forms at bite site - *mild, self-limited, febrile illness* - fever, chills, headache, myalgias - generalized macropapular rash (sparse) - symptoms = one week (non-fatal) - via Rickettsia akari (G- coccobacillus) transmitted via mouse mite bite - urban areas - incubation period = 7-10 days - treatment = *doxycycline*, quinolones

Shigella diagnosis

- isolation from *stool* - selective media - *no black line/H2S production* Shigella... - *non*motile - does not ferment lactose - humans = only hosts - strikes preschool age children & populations in nursing homes - transmission = fecal-to-oral route via fecally contaminated water & hand-t-hand contact - never considered part of normal intestinal flora - diarrhea = flecks of bright-red blood & pus (white cells)

Diagnosis of Legionella

- lab - culture - fluorescent Ab staining - urinary antigen test (Lp1 specific) - Ag can persist Problems... - misdiagnosis = not able to culture organism or infection with one not detected by urine antigen test - 25% mortality rate - cannot perform susceptibility testing - macrolides of fluroquinolones

How to diagnose Proteus

- lab culture - lactose-negative - swarming motility - urease + - UTIs in symptomatic patients (>100,000 colony-forming units/CFUs) on exam - persistently alkaline urine with positive Proteus culture = prompt exam for renal calculi - color change form yellow to pink via increased pH

Vaccination for prevention of Brucella in cattle

- live attenuated brucella vaccine - vaccine accidents can cause human infections

Progression of meningitis

- often develop over 1-4 days - severe case; serious illness develops in 1 day rapid progression... - sudden onset - nonspecific for 4-6 hours - signs of sepsis by 8 hours - meningitis within 15 hours - near death by 24 hours

Plague progression

- onset of *bubonic plague* = 2-6 days after exposure - fever, headache, general illness - buboes may appear within day or so of symptoms - *septicemic plague* via dissemination via blood to many organs - lung infection = *pneumonic plague*

Result of plating E. coli on MacConkey Agar

- organisms turn pink = pH indicator - can utilize lactose - salmonella grows in high salt medium but doesn't turn pink

Mechanism of *Typhoid Fever* caused by Salmonella Serovars

- pass through cells lining the intestinal mucosa --> engulfed by macrophages - replicate after transport to liver, spleen, bone marrow - 10-14 days after ingestion = fever, headache, other aches & pains, malaise, anorexia - one week or longer after symptom onset = GI symptoms, bacteremic phase, colonization of gallbladder & reinfection of intestines - invades regional lymph nodes --> seeds multiple organ systems - bacteria phagocytosed by monocytes --> can survive intracellularly = facultative intracellular parasites - starts 1-3 weeks after exposure - diffuse or localized to right lower quadrant (over terminal ilium) = mimicks appendicitis - spleen may enlarge - transient rash = small pink marks seen only on light-skinned people

Transmission of Helicobacter

- person to person - 50% of patients with H. pylori gastritis are positive for "the bug" in their dental plaque

Multiple infections in hospital unit can indicate a need for strain *source identification*...

- phage typing - bacteriocin typing - restriction digest, then *pulsed field gel electrophoresis* (PFGE) - multi-locus sequence typing (MLST) - whole genome sequencing

Extrinsic resistance of P. aeruginosa

- plasmid transfer to/from neighboring bacteria - has 8 plasmid groups --> *horizontally* exchange resistance genes from neighboring organisms - variety of beta-lactamase enzymes transferred in this manner (*NDM-1 metallo-beta-lactamase*, carbapenemase)

Result of plating Klebsiella on MacConkey

- positive for fermenting lactose = pink - high salt & lactose

Epidemiology of Shigella

- primarily pediatric = 70% of cases in children <15 years old - endemic disease in adults = men who have sex with men, household members of infected children - epidemic outbreaks = daycares, nurseries, custodial care centers - transmitted via fecal-oral route - commonly transmitted via contaminated hands, water, food

Vibrio cholera Treatment

- prompt: fluid & electrolyte replacement before fluid loss leads to shock - antibiotic therapy can help reduce bacteria & toxin production but is secondary to fluid replacement - *doxycycline or tetracycline for adults* - *furazolidone for pregnant women* - *trimethoprim-sulfamethoxazole for children* - O139 strains often resistant to furazolidone & trimethoprim-sulfamethoxazole

Vaccine for B. pertussis

- required by law in US - historically = heat-killed phase I cells - current vaccine is *acellular* - immunity not life-long - DTaP DTaP... - give in 5 doses for children - ages 2 months, 4 months, 6 months, 15-18 months, 4-6 years - booster recommended at 11-12 years old D-Diphtheria toxoid T-Tetanus toxoid P-Whole killed phase I bacterial cells aP-Pertussis toxoid, adhesin proteins (acellular pertussis) - DTaP & Tdap = acellular formulations - vaccine escape mutants = strains negative for pertactin (included in acellular vaccine) identified in several countries Tdap = adult vaccine recommendation - Tdap once - Td every 10 years

Pathogenesis of Mycoplasma pneumonia

- usually extracellular, but may replicated intracellularly - adhesion --> ciliostasis (loss of ciliated cells) --> cell destruction --> *reduced ciliated clearance* - *persistent, non-productive cough* - usually *self-limited* & non-fatal - following transmission via respiratory route, organism attaches to respiratory epithelial cells with help of protein P1 (adhesin virulence factor) - 7% of patients can develop erythema multiforme or Stevens-Johnson syndrome Diagnosis - Cold agglutinins - Complement fixation test - Sputum culture - Mycoplasma DNA probe - PCR Treatments - macrolides, tetracyclines, quinolones = atypical coverage (for Mycoplasma, Legionella, Chlamydia)

Treatment & prevention of Pertussis

- usually supportive - respiratory - droplet precautions for contacts - treatment = *erythromycin or azithromycin* --> does not cure disease but reduces length if given before paroxysmal stage (still inhibits transmission after 5 days of antibiotic) - vaccine = effective B. Pertussis - pertussis toxin: ribosylates Gi & increases cAMP - adenylate cyclase toxin: like anthracis EF toxin - dermonecrotic toxin: LOS; tracheal cytoxin = 100 day cough - culture from deep nasal swab on *Bordet-Gengou agar* (4 days); PCR detection; circulating Ab appear in 3 weeks - *DTaP vaccine* - currently *acellular* = historically heat killed phase I cells; NOT LIFELONG - *phase variation* = phase I smooth virulent --> phase IV rough avirulent colon

ExoT of P. aeruginosa...

ADP-ribosylates Crk protein --> inactivation of Rac --> no wound healing

ExoS of P. aeurginosa...

ADP-ribosylates early host proteins: ezrin, radixin, moesin proteins (ERMs) - blocks phagocytosis - affects motility

ExoY of P. aeruginosa

Adenylate cyclase --> increased cAMP --> disrupts cell shape --> *homoserine lactate production* ExoS - ADP-ribosylates early host proteins: ezrin, radixin, moesin proteins (ERMs) --> affects cell motility ExoT - ADP-ribosylates Crk protein --> inactivation of Rac --> no wound healing of phagocytosis ExoU - *lipase* activity --> quickly kills cells

Pseudomonas always resistant to

Ampicillin SXT CF

Vectors of Human granulocytic anaplasmosis (*HGA*), caused by Anaplasma phagocytophilum

Anaplasma - Black legged ticks - reservoirs = chipmunk, vole, canines HGA tick-borne, infectious disease - Anaplasma phagoctyophilum = obligate intracellular bacterium typically transmitted to humans by ticks of Ixodes ricinus species complex - these ticks also transmit Lyme disease - bacteria infect neutrophils - clinically, HGA is indistinguishable from human monocytic ehrlichiosis & other tick-borne illnesses such as Lyme disease - PCR useful for diagnosis

P. aeruginosa Treatment

Antibiotic combo therapy of *beta-lactam & aminoglycoside* - ticarcillin + tobramycin - piperacillin + tobramycin - ceftazidime + tobramycin - cefepime + amikacin - timentin + tobramycin Fluoroquinolone therapy (can be oral) - ciprofloxacin - levofloxacin - moxifloxacin or gatifloxacin beta-lactam (often with beta-lactamase inhibitor) + aminoglycoside (often tobramycin), advanced cephalosporin, penem, or monobactam Colistin (a polymyxin) = last resort Some think inhaled antibiotics works better than IV - aztreonam, colistin, or tobramycin - nearly impossible to fully eradicate P. aeruginosa from CF lung

Desert/temperate regions of North Africa & Middle East. *primarily oral lesions*, initial lesion often not observed. secondary lesions include oral papules & mucosal patches. *gummas of skin, bone, nasopharynx* can occur later.

Bejel

(TEST): Vector of onchocerciasis (Onchocerca volvulus infection)

Black flies

(TEST): A 23-year-old sheep farmer presents with symptoms of aches, chills, fever, and drenching sweating episodes. He reports that he recently slaughtered three sheep for private consumption. Which one of the following is a likely cause of his infection?

Brucella melitensis

Aches, chills, & fever 7-21 days after exposure to Brucella. Drenching sweating episodes can occur. Can become chronic with relapses during convalescence. Symptoms often vague. <100 cases/year in US. 500,000 world-wide.

Brucellosis/Malta Fever/Undulant Fever - comes & goes with time - get it from unpasteurized dairy

Forms of Plague Disease

Bubonic - inflammation of infected lymph nodes (buboes) Pneumonic - pulmonary form - when organisms spread from bloodstream to lungs or inhaled in aerosol droplets

Campylobacter responsible for gastroenteritis (enterocolitis) especially in children, blood diarrhea (half of patients); also, septicemia, meningitis, spontaneous abortion, proctitis, Guillan-Barre syndrome

C. jejuni C. coli = gastroenteritis, septicemia, meningitis C. fetus = septicemia, GI disease, meningitis, spontaneous abortion

2 most frequently recovered bacterial causes of gastroenteritis in USA

C. jejuni & Salmonella - spread by fecal-oral route with improperly cooked, or cross-contaminated poultry = most important source - water = infrequent vehicle & no evidence for person-to-person spread

3 stages of B. pertussis disease

Cattarrhal = 1-2 weeks Paroxysmal coughing = 2-4 weeks Convalescent

Primary reservoirs of Coxiella burnetii, Q fever agent

Cattle, sheep, goats - wide variety of other animals, livestock, domesticated pets - *usually no clinical disease in animals* - *survive for long periods in environment* - infection of humans usually via *INHALATION* of organisms

(TEST): A cancer patient had septicemia with Pseudomonas aeruginosa and the organism was found to be resistant to ciprofloxacin and other fluoroquinolones. Which of the following would be a good therapy for this infection?

Ceftazidime, a third generation cephalosporin, plus tobramycin (aminoglycoside) C*A*MPF*IR*E

Active trachoma predominately seen in young children

Chlamydia trachomatis Trachoma Serotypes A-C - becomes less frequent & f shorter duration with increasing age (partial immunity) - conjunctival scarring accumulates with age (significant vision loss between 10-30 y/o) - irreversible damage

Most common cause of non-gonococcal & post-gonoccocal urethritis in men

Chlamydial *epididymitis* - Non-gonococcal urethritis - via Chlamydial trachomatis serotypes D-K = urogenital infections

Important cause of bronchitis, pneumonia, sinusitis. Generally asymptomatic, mild in young adults, more severe in adults. Cause of Community Acquired Pneumonia (CAP), usually in children over age 10. More common in males, maybe because of smoking. Incubation period: 3-4 weeks. Initial presentation - gradual onset of *upper respiratory tract symptoms.* Bronchitis & pneumonia follow with rhonchi & rales. Diagnosis: - immunofluorescence staining or complement fixation (CF) serum test for Ab. CF cross-reacts with C. psittaci, C. trachomatis. PCR (experimental). Tissue culture (research labs only).

Chlamydophila pneumoniae treatment: - *azithromycin*, clarithromycin - alternatives: doxycycline, tetracycline - erythromycin for children, pregnant women

Diagnosis of Coxiella burnetii, Q fever agent

Clinical signs & symptoms Serology - IFA for *IgG & IgM Ab* to phase I (spore-like forms) & phase II (large cell forms) Ag on *paired sera* = acute Q fever (primarily Phase II Ag); chronic Q fever (phase I & II Ag) PCR Q fever - no arthropod vector - spores inhaled as aerosols from cattle/sheep amniotic fluid - presents as pneumonia - most common cause of culture negative endocarditis - has no rash or vector - causative agent can survive outside in its endospore form - not in the Rickettsia genus but closely related TEST!! *Increasing antibodies used to diagnose Coxiella burnetti, Rickettsia, prowazekii, Borrelia burgdorferi*

An immunosuppressed patient who lived in the New Mexico desert for several years has recurrent lung infections that have not been cured by anti-bacterial treatments. A sputum specimen is cultured at room temperature (25 C) and the structures illustrated are demonstrated. What is the most likely diagnosis for this patient's infection?

Cocidioides immitis

Mechanism of Vibrio cholerae Cholera Toxin

Complete A-B toxin (similar to heat-labile toxin / LT of E. coli) - 5 identical B subunits bind to *ganglioside GM1* on intestinal epithelial cells - A subunit becomes internalized --> activates adenylyl cyclase --> cAMP - ATP catalyzed to cAMP & hypersecretion of electrolytes - 1 liter of water can be lost/hour, but bacteria not all flushed out because of adherence to mucosal cells

Associated disease: Chlamydia trachomatis serotypes D, E, F, G, H, I, J, K

Conjunctivitis - *Adult Inclusion Conjunctivitis* in sexually active adults - *Neonatal Conjunctivitis* - congenital Pneumonia - *Infant Pneumonia, rhinitis, cough* Urogenital infections - *STD* - non-gonococcal urethritis, cervicitis, salpingitis, proctitis, epididymitis Reiter's Syndrome - urethritis, conjunctivitis, poly-arthritis & mucocutaneous lesions; possible sequela to genital infection

Most common agents of PID

Ct & N. gonorrhea

Nutritional requirements of Bodetella pertussis

Culture on *Bordet-Gengou Agar*: charcoal, glycerin, potato starch, blood - gram-negative rod (coccobacillus) - oxidizes *AAs* by respiration (cannot ferment carbs) - non-motile - non-sporeformer - encapsulated

In a patient with Sporotrichosis, your patient presents with a localized pustule that has progressed to an ulcer at the site where he pricked his finger working in the garden. During the physical examination you note several nodules along the lymphatic drainage from the lesion. How would you definitively diagnose this condition?

Culturing the organism at 25 degrees to demonstrate rosettes of microconidia extending at right angles from vegitative hyphase

Pseudomonas Proteases

Elastase A (LasA) - unknown Elastase B (LasB) - destroys host defense molecules - degrades elastin of blood vessels - tissue damage Alkaline protease (AP) - destroys host defense 'cules - exposes receptors Protease IV (PIV) - destroys host complement & lung surfactant 'cules PASP - degrades collagen

Disease caused by: R. typhi Orientia tsutsugamushi

Endemic or Murine typhus - fleas Scrub typhus - mites - reservoir = rodents, squirrel fleas, rodent - febrile illness, rash (centrifugal) above plus eschar & lymphadenopathy - diagnosis = serology - treatment = *doxy*, chlor, rif

Disease caused by B. hermsii, B. turicatae, B. parkerii, (15 species)

Endemic relapsing fever, TBRF - soft tick borne - vector = soft ticks - reservoir = rodents, small mammals, ticks = recurrent fevers (3-10), febrile illness - diagnosis = blood smears, culture, serology - treatment = *tet*, eryth

(TEST): When Neisseria meningitidis attaches to epithelial cells via pili, which one of the following is likely to occur?

Engulfment of the bacteria

E. coli associated with hemolytic uremic syndrome

Enterohemorrhagic (EHEC)

E. coli associated with hemorrhagic colitis

Enterohemorrhagic (EHEC)

E. coli causing GI disease divided into 5 groups (virotypes)

Enteropathogenic (EPEC) - *infant diarrhea* Enterotoxigenic (ETEC) - Traveler's diarrhea, *infant diarrhea* Enterohemorrhagic (EHEC) - blood diarrhea, hemorrhagic colitis, hemolytic uremic syndrome Enteroinvasive (EIEC) - Bacillary dysentery Enteroaggregative (EAEC) - *Infant diarrhea*, traveler's diarrhea 6th group added but not as well characterized = Diffuse-adhering E. coli (DAEC) - infant diarrhea

Disease caused by Borrelia recurrentis

Epidemic relapsing fever, LBRF-louse born - vector = body lice - reservoir = humans = recurrent fever, febrile illness - diagnosis via blood smears, culture, serology - treatment = *tet*, doxy, eryth - recurrent due to variable surface antigens

Transmitted by body lice (Pediculus), LBRF via skin abrasions by hemolymph of crushed lice. More severe disease. Untreated = 10-40% mortality. Only imported cases seen in USA.

Epidemic, Borrelia recurrentis

Lyme Disease Treatment

Erythema migrans/facial palsies/mild cardiac disease in early localized or early disseminated disease = *doxycycline*, amoxicillin, cefuroxime axetil Neurologic disease/cardiac disease (AV block)/arthritis = *ceftriaxone/cefotaxime IV* - doxycycline, amoxicillin, or cefuroxime axetil hospitalization if symptoms severe - co-infection possible = Babesia, Anaplasma

Obligate intracellular development of Rickettsia, Orientia, Coxiella, Ehrlichia, & Anaplasma

Escape endocytic vacuole, replicate in cytoplasm - Rickettsia in endothelial cells of small blood vessels - Orientia also in small blood vessel epithelium & in macrophages - *vasculitis/rash for Rickettsia & Orientia* Remain in endocytic vacuole in host cell (morulae) - Coxiella & Ehrlichia in monocytes & macrophages - Anaplasma in neutrophils

Pathogenesis of Campylobacter

Fever *Greenish watery foul-smelling diarrhea* maybe followed by diarrhea, severe abdominal pain usually self-limiting transmission... - contaminated or under-cooked food / poultry - domestic animals = asymptomatic carriers - detection via bacteria in stool cultures

Campylobacter Treatment

GI disease - fluid & electrolytes *Severe* gastroenteritis & septicemia - *erythromycin or azithromycin* = drugs of choice - also: *tetracyclines or fluoroquinolones* - resistant to penicillins, cephalosporins, & sulfonamides - increasing resistance to ciprofloxacin - prevention & control = proper food preparation, avoiding unpasteurized milk, preventing contamination of water supplies

Diagnosis of H. pylori

Gastric biopsy - histological exam - urease testing - PCR based testing Non-invasive urease test - C14-based urea breath test (UBT) - urea production due to urease enzyme in stomach Anti-H. pylori antibodies in serum Asymptomatic patients (non-ulcer dyspepsia) - look for anti-H. pylori Abs in serum Symptomatic patients (active infection) - UBT (urea breath test) Patients with severe symptoms of peptic ulcers - gastric biopsy

Diseases associated with H. cinaedi & H. fennelliae

Gastroenteritis Septicemia Proctocolitis

Diagnosis of Gonorrhea

Gram stain (G- diplococcus) Culture *PCR* (Aptima test) *Point-of-care* antigen capture of nucleic acid hybridization

Intracellular Gram-negative coccobacillus. Endemic in tropical & subtropical regions of south-east India, Indonesia, Papua New Guinea, Central Australia, South Africa, & South America. Non-sexual transmission possible. Small, relatively painless, *erythematous pustules or subcutaneous nodules*. Ulcerate to produce *shallow, sharply demarcated lesions*. *Extra-genital lesions* possible, especially oral lesions. Causative agent is Calymmatobacterium granulomatis.

Granuloma inguinale - Donovanosis diagnosis - stained (Wright's Giemsa, Silver) scrapings or punch biopsies of lesions show intracellular bacteria treatment: - *azithromycin*, doxycyline, erythromycin, tetracycline, TMP/SMX

The Bile-Esculin test differentiates what organisms?

Group D Streptococcus & Enterococcus from other Streptococcus

Result of Non-fermenter on TSI

Growing on amino acids = somewhat *alkaline* reaction on slant

Disease caused by Anaplasma phagocyophilum E. ewingii

HGE/HGA - Human Granuloctyic Ehrlichiosis/Anaplasmosis - vector = ticks - reservoir = chipmunks, voles, canines, ticks = febrile illness, diagnosis = serology, PCR, blood smear - treatment = *doxy*, rif

Disease caused by Ehrlichia chaffeensis

HME - Human Monocytic Ehrlichiosis (*MEGA*) - vector = ticks - reservoir = deer, domestic dogs, ticks = febrile illness, rash in pediatric patients - diagnosis = serology, PCR, blood smear - treatment = *doxy*, rif

An example of a Gram negative, indole positive pathogenic species is

Haemophilus influenza

Haemophilus influenza is extremely fastidious & thus require supplementation for culture in vitro. What correctly describes the 2 requirements known as X factor & V factor?

Hemin & NAD

Your patient is a poultry farmer who developed a respiratory illness after cleaning out the chicken pens. Intracellular yeast are seen in the histiocytes in the patient's liver. The sputum is cultured at room temperature (25 C) and the structures illustrated were found. What is the causative organism?

Histoplasma capsulatum

Obligate intracellular bacteria that parasitize

Human Monocytic Erlichiosis - E. chaffeensis = *HME* (Morulae in cytoplasm of *monocyte* Human Granulocytic Anaplasmosis - E. ewingii or A. phagocytophila = *HGE/HGA* (morulae in cytoplasm of *neutrophil*) Hard tick transmitted - HME - Long Star ticks - HGE/HGA - Ixodes sp. ticks

Most common STI worldwide

Human Papillomavirus Infection HPV types 6 & 11 --> 90% of genital warts HPV types 16 & 18 --> 75% of cervical cancers

Most infections occur in what location?

ICUs - increased occurrence with increased stay

(TEST): Geographical mobility of Americans tends to do what to mycoses?

Increase the incidence of mycoses

Treatment for Ehrlichiosis & Anaplasmosis

Initiate immediately if HME/HGE suspected - *doxycycline* - rifampin for doxycycline sensitive patients & pregnant women Ehrlichiosis - vector = tick - monocytes with morulae Anaplasmosis - vector = tick - granulocytes with morulae

Gram-negative coccobacillus. Colonizes human oropharynx. Opportunistic pathogen. Subacute endocarditis, HACE*K*.

Kingella kingae - usually susceptible to penicillin, tetracyclines, erythromycin, fluroquinolones, & aminoglycosides - invasive infection seen in children six months to four year - infections of joints & bones - infrequent bacteremia - often confused with other clinical conditions.

"Fish eye" colony. Initially digesting Lac (makes acid). When Lac consumed, digests amino acids (neutral).

Klebsiella

A 25-year-old male who is visiting the U.S. from Vietnam presents with granulomatous lesions on his genitals and in the groin area. He said that the lesions began as nodules under the skin. You send scraped portions of the affected tissue to the hospital laboratory and order a Giemsa stain. The stain shows small bacteria in the shape of rods inside the polymorphonuclear leukocytes (PMNs) of the tissue. Which of the following genera is the etiologic agent of your patient's infection?

Klebsiella

(TEST) Bacterium common cause of liver abscesses in alcoholics

Klebsiella - prone to pneumonia = bloody sputum

(TEST): A 65-year-old male with a history of chronic alcohol abuse presents with a severe respiratory infection. His sputum sample is tinged with blood, and X-rays confirm pneumonia. Efforts to treat his infection with beta-lactam antibiotics have failed. Laboratory findings indicate that the infecting organism is a Gramnegative, lactose-fermenting bacterium producing the New Delhi metallo-beta-lactamase. The pathogen most likely causing this patient's disease is

Klebsiella pneumonia

A. baumannii grows on

MacConkey Agar - non-lactose fermenting = pink - oxidase-negative - can often be confused with pneumococcus

Treatment of Leptospirosis

Mild cases = doxycycline, amoxicillin Severe cases (Weil's SPHS) = IV penicillin G, IV ceftriaxone kidney dialysis may be necessary supportive therapy

Third leading cause of otitis media in young children.

Moraxella catarrhalis - gram-negative diplococci - aerobic & oxidase positive - bronchitis & bronchopneumonia in elderly patients with chronic pulmonary disease - most strains produce beta-lactamase (indirectly protects other pathogens from penicillin) - colonizes upper respiratory tract of infant & children - resembles Neisseria in culture - often exacerbates COPD - colonization of adults usually short-lived - new strains frequently acquired

(TEST): A one microliter volume of correctly collected urine (clean catch) was streaked onto a blood agar plate and incubated overnight at 37 °C. At least how many colonies would need to form on this inoculated agar plate to prove that the patient had a urinary tract infection?

More than 100,000 colonies

Signs/Symptoms of Bacterial Vaginosis

Most women actually asymptomatics but... - abnormal *vaginal discharge*, usually *white/gray, can be thin* - amine odor after KOH addition (unpleasant, strong *fishy*) - elevated vaginal *pH > 4.5* - >20% of "*clue cells*" (vaginal epithelial cells with adherent bacteria) - dysuria & itching may also occur 3/4 of symptoms above = BV diagnosis Nugent score (1-10) based on number of large Gram-positive bacilli vs. smaller anaerobes (G-) Treatment = metronidazole

(TEST): One of the antibiotics that most directly affects DNA

Moxifloxacin

Bacteria characterized by wispy x-ray & fried egg appearance of colonies.

Mycoplasma

Treatment for Mycoplasma & Ureaplasma STIs

Mycoplasma - *tetracycline*, clindamycin Ureaplasma - *erythromycin*, tetracycline - detected via PCR

Smallest free-living bacteria

Mycoplasma & Ureaplasma - will pass through 0.45-um filters - no detection by light microscopy - requires exogenous sterols - facultative anaerobes (M. pneumoniae = strict aerobe)

Patchy Broncho-pneumonia is characteristic of

Mycoplasma/Atypical Pneumonia: *Lower respiratory Infection*: Walking Pneumonia Broncho-pneumonia - *diffuse patches* in lobes of both lungs, especially in lower field of middle zone - pale tan regions of parenchyma are normal - reddish brown regions of parenchyma contain hemorrhage &/or neutrophils

Which Neisseria does not have a capsule?

N. gonorrhea

STD that can cause polyarthritis

N. gonorrhea - young sexually active person that shows up with asymmetric arthritis - joint tap = doesn't gram stain because infection is intracellularly

Prevalence & Mortality of Neisseiria

N. gonorrhoeae - high prevalence; low mortality N. meningitidis - low prevalence; high mortality

Neisseria species that are commensals in oropharynx. Implicated in cases of meningitis, osteomyelitis, endocarditis, bronchopulmonary infections, acute otitis media, acute sinusitis. Most isolates susceptible to penicillin.

Neisseria *sicca* & Neisseria *mucosa*

(TEST): Vibrio cholerae utilizes the following factor that modifies the host cell surface by cleaving sialic acid, leading to exposure of increased ganglioside GM1 sites for binding by cholera toxin.

Neuraminidase

Commonly given for UTIs but *not* effective for Proteus

Nitrofurantoin

Treatment for Genital Herpes

No effective treatment - antivirals reduce duration & severity of outbreaks - *acyclovir*, valaciclovir, famciclovir

Recognize Pseudomonas on Blood Agar & MacConkey Agar

Non-Mucoid Pseudomonas: Lactose Negative - obligate aerobic = non-lactose fermenter - gram-negative rod - most make some kind of pigment - produces green fluorescent pigment (fluorescein) & blue pigment (pyocyanin) - mechanism for detoxifying oxygen radicals - can see it on blood plates - metallic sheen

Diseases caused by Treponema pallidum subspecies endemicum, pertenue, & carateum subspecies pallidum

Non-venereal treponemal infection (Bejel, Yaws, Pinta) - via *skin contact*

Tropical areas of South and Central America. Young adults. Small, multiple, puritic papules that *enlarge & persist* years. Often accompanied by *regional lymphadenopathy*. *Disseminated, recurrent lesions* in 3-9 months that become pigmented with age. Tertiary leads to disfiguring pigment changes & scarring, skin has mottled appearance. Skin is only organ involved, no congenital form exsists.

Nonvenereal Treponemal Infection: *Pinta* - least severe of treponemal infections limited to skin - transmitted via skin-to-skin contact (similar to bejel & yaws) - after weeks: produces raised papule = enlarges & becomes hyperkeratotic (scaly/flaky) - present in sun exposed surface of arms & legs - months later = further thickened & flat lesions (pintids) appear all over body = widespread pigmentary change with mixture of hyperpigmentation & depigmentation - treatment = penicillin, tetracycline, azithromycin or chloramphenicol

What do Candida, Cryptococcus, Aspergillus, Mucor and Rhizopus have in common?

Opportunistic infections

Flagella of Enterobacteriaceae

Peritrichous

Diseases caused by Chlamydophila psittaci

Parrot fever Ornithosis Psittacosis = atypical pneumonia = 1-3 weeks after exposure - inhalation of dried bird feces, urine, respiration secretions

(TEST): Treatment for syphilis

Penicillin

Treatment & Prevention of Neisseria meningitidis

Penicillin *Cephalosporins*, 3rd generation - needs to penetrate BBB = ceftriaxone Immunoprophyalxis: MCV4 & B vaccine; *rifampin* Current recommendations for 11 to 12 y/o boost at college

Treatment of Nonvenereal Treponemal Infections (Yaws, Bejel, Pinta)

Penicillin G (IM) Oral doxycycline, tetracycline, or erythromycin

Stain that allows differentiation of fungus from human tissue by staining the fungus a pink-red color

Periodic acid-Schiff stain - turns fungi a pink-red color

Klebsiella Diseases

Pneumonia - necrotic destruction of alveolar spaces - formation of cavities - production of blood-tinged sputum - enteric is encapsulated (O Ag) but non-motile (no H Ag) - causes sepsis (2nd most common after E. coli) - sputum looks like red currnt jelly = color of O Ag capsule - mortality is high despit antibiotic therapy Wound infections Soft tissue infections *UTIs* *Liver abscesses in alcoholics & diabetics* *Granulomatous disease of nose* *Granulomatous disease of genitals or inguinal (groin) area ("granuloma inguinale" or donovanosis")*: K. granulomatis - rare in US - endemic in Papua New Guinea, Caribbean, South America, India, southern Africa, Vietnam, Australia - transmitted after repeated exposure through sexual intercourse or nonsexual trauma to genitalia - prolonged incubation (weeks or months) - appearance of subcutaneous nodules --> break down = granulomatous lesions

Neisseria meningitidis virulence factors

Polysaccharide capsule - Interferes with phagocytosis - Serotypes A, B, C, 29-E, H, I , K, L, W-135, X, Y, and Z - A, B, C, Y, and W-135 about 90% of infections Lipooligosaccharide (LOS); endotoxin Pili - attachment to epithelial cells - resistant to killing by neutrophils - phase variation; antigenic variation in pilin proteins PorB proteins - outer membrane proteins that form pores - facilitates bacterial invasion into epithelial cells Opacity (Opa) proteins - outer membrane proteins - binding to epithelial cells - where organism has to liver Reduction-modifiable protein (RMP) - outer membrane protein - IgG & IgA1 Abs directed against RMPs interfere with bactericidal action of Abs directed against LOS Transferring & lactoferrin binding proteins - acquisition of iron IgA1 protease *Membrane blebs (contain LOS & surface proteins)* - many enhance endotoxin-mediated toxicity & protect bacterial cells form Abs - outer membrane vesicles - break off from outer membrane

Urease Reaction of Proteus

Positive

Physicians should be particularly alert to the dangers of mycotic infections among patients with which risk factors? Multiple Answer Question - all answers could be correct.

Radiation therapy Immunosuppression Long term antibiotic therapy Chemotherapy for Cancer of other debilitating or metabolic diseases

How to diagnose Genital Herpes

Rapid Ag & Ab tests commercially available - serology for Abs (cannot distinguish HSV-1 & HSV-2) - culture - PCR (distinguishes HSV-1 & HSV-2) - Ag detection

Common presentation of E. chaffeensis (HME)

Rash in *children* = 60% of children

Fatty acid linke to rhamnose & acts as surfactant 'cules in Pseudomonas. Have been implicated in numerous virulence-associated effects such as increased inflammation.

Rhamnolipids

Endemic or Murine Typhus caused by

Rickettsia typhi - rodent reservoirs - vectored by their fleas & cat fleas - via feces/abrasions, *not flea bite* - gradual onset - fever, rash (chest & abdomen --> palms & soles) - diagnosis = clinical signs, serology for Ab - treatment = *doxycycline* (alternatives = chloramphenicol, rifampin)

Predisposing factors to Legionella

Risk factors - cigarette smoking - chronic lung disease - immunosuppression Environmental factors - high humidity - increased rainfall

Salmonella serovars more commonly associated with causing bacteremia

S. choleraesuis S. paratyphi S. typhi

4 species of Shigella containing 45 O-antigen-based serogroups

S. dysenteriae S. flexneri - most common in underdeveloped countries S. boydii S. sonnei - most common in developed countries

Salmonella genus consists of 3 species:

S. enterica - clinically important species - contains serovars (serological variants) S. bongori S. subterranean

Results from bite of Lone star tick (Amblyoma americanum).

STARI - Southern Tick Associated Rash Illness - etiologic agent not identified - circular rash resembling early Lyme disease - lesion smaller & typically single - fever, headache, fatigue, myalgia - not linked to arthralgia, neurologic disease or chronic symptoms - treatment = *doxycycline*

Most common cause of PID

STIs, especially repeat infections - *Chlamydia* = most common cause of PID, N. gonorrhoeae also

In what syphilis stages do systemic symptoms become present?

Secondary/Tertiary

What grows on MacConkey Agar

Selective: inhibits gram-positives Favors *gram-negatives* Only non-fastidious bacteria = Enterobacteriaceae & Pseudomonas Differential - tests for lactose utilization - *acid production --> red color* = lac-positive - neutral red accumulates in colony - lac-negative grow on amino acids (neutral pH) - this is different from CTA where yellow indicates acid production

E. coli exotoxins

Shiga toxin (Stx-1, Stx-2) Heat-stable toxins (STa, STb) Heat-labile toxins (LT-I, LT-II) Hemolysins (Hly)

Mechanism of toxin Shigella dysenteriae produces

Shiga toxin (like EHEC) = classic A-B toxin - B subunit binds host GB3 - A subunit enters cell --> cleaves 28S rRNA in 60S ribosome subunit = prevents binding of tRNA & halts protein synthesis - primary toxin action = destruction of intestinal epithelium - in a few patients, toxin will damage glomerular cells & cause HUS

Characteristic of genital ulcers caused by Herpes

Small, painful, pruritic vesicles lesions shallow, *usually multiple, grouped*, and may coalesce - lymphadenopathy = tender, firm, *bilateral* nonsuppurative inguinal adenopathy

(TEST): Pseudomonas aeruginosa fails to grow in TSI agar except close to the surface in the slant portion of the medium. These bacteria would grow in the but portion of the medium if which of the following were present?

Some nitrates

A dimorphic fungus causes coccidioidomycosis. Which one on the following forms of this fungus is seen when growing in a human host at 37 °C?

Spherules Coccidiomycosis - 5-10% = erythema nodosum = delayed type HS response to fungal Ags (no organisms in nodule) - dimorphic = mycelial phase in env't (arthrospores or arthroconidia) or spherules within endospores inhost - can be an AIDS-defining illness = leading mycotic infection in southwest

Coagulase test differentiates...

Staphylococcus epidermidis from Staph aureus

Progression of rash in Epidemic, Endemic, & Scrub Typhus

Starts on trunk --> spreads outward toward limbs = *centrifugal spread* Endemic (fleas) - R typhi Epidemic (human body louse) - R prowazekii

Tinea unguium or dermatophytic fungal infection of the toe or finger nails can be caused by which two genera of fungi?

Trichophyton Epidermophyton

Diagnosis of Trichomoniasis

Wet Mount - detects 40-50% Culture - Tv - takes 2-5 days to grow out - >90% sensitive PCR - Aptima test - takes 3-4 days Colposcopy - Colpitis Macularis PAP smears - equal to wet mount in sensitivity but more difficult *Point of care* Ag detection

Target peptidoglycan in bacteria. P. aeruginosa made its own inhibitor that neutralizes these toxins for self-protection.

Tse toxins = Type VI Secretion - resembles phage - has been shown to act as counterattack system to aggressive competitors - also injects proteins (similar to type III) - induced during iron starvation & dense bacterial growth - via P13K/Akt pathways (activation of Akt = actin remodeling) - secreted proteins = 2 phospholipases D (PldA & PldB) --> bind & activate Akt

Diseases caused by Chlamydia trachomatis, serotypes D-K & serotypes L1, L2, L3

adult conjunctivitis neonatal conjunctivitis/pneumonia chlamydia (STI) LGV (STI)

(TEST): Tinea, the clinical designation for cutaneous fungal infections, may be caused by any one of three major genera of fungi: Trichophyton, Microsporum, or Epidermophyton. An infection of the groin would be referred to as

Tine cruris = jock itch = patients develop itchy red patches on groin & scrotum

Associated disease: Chlamydia trachomatis Serotypes A-C

Trachoma - *follicular conjunctivitis* - hyperendemic blinding trachoma - Middle East, North Africa, India - can lead to *blindness* after multiple re-exposures that maintain intense inflammation in conjunctiva - white lumps under eyelid - watery discharge - secondary bacterial infections - scarring of eyelid --> distortion of eyelids & lashes rub on eye = *trichiasis*

Leading infectious cause of bindness (7th overall)

Trachoma = endemic

Human Trichomonads associated with periodontal disease

Trichomonas *tenax* (commensal, oral secretions/cavities)

Human Trichomonads associated with commensal, intestine/stool

Trichomonas hominis

Most common Proteus disease

UTI - *urease* splits urea into CO2 & ammonia --> raises urine pH & causes renal stones - increased pH also toxic to uroepithelium - can cause *biofilms* on urinary catheters - P. mirabilis, P. vulgaris, P. penneri

(TEST): Which of the following clinical forms of disease most frequently occurs due to infections with Francisella tularensis?

Ulceroglandular

Urethral smear with >4 PMNs per high power field (x1000) is indicative of

Urethritis - also gram stain for gonococcus - urethral discharge in men - *Neisseria* & *Chlarmydia* = major STI pathogens - in areas of *high Trichomonas prevalence*, this STI should also be considered as a cause of urethritis

Factor requirements for H. parainfluenzae (teeth)

V

Induces chloride ion secretion in epithelial cells by increasing intracellular calcium. Used as detection in classifying virulent strains. Produces beta-hemolysis on blood agar (made with human blood). *Virulent* strains are called *Kanagawa positive*. Toxin co-regulated pili. Chemotaxis proteins.

V. *parahaemolyticus* thermostable direct hemolysin - TDH (Thermostable Direct Hemolysin) - Kanagawa hemolysin

Vibrio species from water and food. Causes gastroenteritis.

V. cholerae

Which Vibrio can grow without salt?

V. cholerae - most of the other pathogenic species are halophilic = tolerate wide pH range but are susceptible to stomach acid

Chromosomal material of Vibrio

V. cholerae & V. vulnificus = *2 circular chromosomes (most bacteria have 1)* - each chromosome is essential

Disease caused by T. pallidum pallidum

Venereal Syphilis (STD)

Monitor biochemical tests by color change. Also have cards to determine antibiotic resistance.

Vitek cards

Describe Lower Respiratory Infection caused by Mycoplasma/Atypical Pneumonia

Walking pneumonia - patchy broncho-pneumonia seen on chest x-ray - typically more impressive than physical findings - resolves slowly = "incomplete immunity" - secondary infections can occur secondary complications... - *erythema multiformed (Stevens-Johnson Syndrome)* (children) - hemolytic anemia, myocarditis, pericarditis, arrhythmias, renal dysfunction, encephalitis

Factor requirements for H. haemolyticus (oropharynx)

X, V

Factor requirements for H. influenza (nasopharynx)

X, V

If a lactose- & glucose- fermenting organism that has a fully functional lac operon is grown for twenty-four hours on TSI media, what color will result?

Yellow (acidic) slant/Yellow (acidic) butt

Agent of Bubonic Plague

Yersinia pestis - small gram-negative rod - *bipolar staining (safety pin)* - *encapsulated = protein capsule* - facultative anaerobe - takes 48-72 hours to form colonies - better growth at 30 C

(TEST): Antibiotic resistance genes have better chance to mutate when they are part of

a non-conjugal plasmid

(TEST): Acinetobacter baumannii is well adapted to the hospital environment. A. baumannii persists in the hospital because it is

able to form biofilm

A red color in the slant portion of a TSI culture indicates that the organism present can cleave

amino acids, yielding ammonia

(TEST): Urease production causes the urease test media to turn a bright reddish color. This is due to

ammonia production causing an alkaling pH

(TEST): A patient with pneumonia is found to have Pseudomonas aeruginosa in his sputum. He was started on ti mentin and tobramycin. This therapy is

appropriate & likely sufficient for this infection

(TEST): Nosocomial infections...

are very common in the United States (approximately 1 in 20 hospitalizations)

(TEST): Fleas play an important role in the transmission of Yersinia pestis because the

bacteria proliferate within the flea

Patient presents with paranasal swelling & bloody exudate form both his eyes & nares, & he is nearly comatose. Necrotic tissue in the nasal turbinates show nonseptate hyphae consistent with Rhizopus, Mucor, or Absidia (phylum Zygomycota, class Phycomycetes). What is the most likely compromising condition underlying this infection?

being a ketoacidotic diabetic

Some members of Enterobacteriaceae lack lactose operon & cannot grow on disaccharides. The lactose operon consists of genes for importing lactose into the cell (beta-galactosidase permease), metabolizing lactose (beta-galactoside transacetylase) & which enzyme for splitting the disaccharide lactose into glucose & galactose.

beta-galactosidase

Bacitracin test differentiates...

beta-hemolytic Group A streptococcus from beta-hemolytic Group B streptococcus

Brucella canis associated with what animals?

dogs

Treatment for STARI - Southern tick-associated rash illness

doxy - fever, rash, muscle pain, fatigue

(TEST): Sulfa-trimethoprim...

drug combination that is only bacteriostatic if used for tissue infections because the bacteria acquire some metabolites that they cannot synthesize

HSV-1 (oral, fever blisters) & HSV-2 (genital) replicate locally in

epithelial cells (especially mucosal epithelium) infection.. - small, painful, usually *multiple, grouped vesicles* (blisters) with red based within 2-7 days - vesicles ulcerate = *shallow lesion*, heals 2-4 weeks - fever, malaise, bilateral lymphadneopathy (firm, tender) - *recurrent outbreaks* weeks/months later, especially during stress (5 / year) - outbreaks preceded by *prodromal signs* of tingling & pain at eruption site 1-2 days prior to outbreaks

V. parahaemolyticus treatment: GI disease

fluids & electrolytes antibiotics in severe cases - milder cholera-like disease

(TEST): When inoculated in triple sugar iron (TSI) agar slants, E. coli preferentially metabolizes which component of this medium first?

glucose

Bubbles of gas in the but of the TSI culture, or movement of the entire agar plug towards the top of the tube, indicate the organism present can metabolize

glucose, producing carbon dioxide

Chronic Q fever is seen almost exclusively in patients with

heart disease or valve defects (90%), immunocompromised, & pregnant women - subacute endocarditis common - spontaneous abortion, premature labor - Ab to both phase I & phase II Ags (LPS) - mortality = 25-60% - post Q-fever fatigue syndrome

(TEST): A 48-year-old female with end-stage renal disease undergoes renal transplantation. After surgery, the patient receives immunosuppressive therapies, including Belatacept, which is a CTLA-4 - Ig fusion protein. Belatacept is used because of its ability to directly

inhibit T cell co-stimulation

Type b H. influenza most often occurs in children...

lacking specific antibodies

EIEC difficult to distinguish because...

large virulence plasmid can get lost in vitro

Vibrio vaccines

non licensed for use in U.S. but 2 vaccines have been manufactured Dukoral - licensed in 60 countries - inactivated whole cells plus recombinant CT *subunit B* ShanChol - licensed in India - inactivated whole cells minus CTB

(TEST): A 19 year old male comes to the health department and requests evaluation for penile discharge lasting 3 days. Physical exam reveals a yellow urethral discharge but no other abnormalities. The gram stain of the discharge reveals gram-negative intracellular diplococci and is shown below. Nucleic acid amplification tests of the discharge are performed for Neisseria gonorrhoeae and Chlamydia trachomatis. The patient states he is unlikely to keep a follow up appointment because of his college schedule. Your treatment plan for this patient should consist of treatment for

nongonococcal urethritis & gonococcal urethritis, plus serologic testing for HIV

Characteristic of genital ulcers caused by *Primary syphilis*

painless, indurated, round red smooth base, *usually single*, sharple demarcated - lymphadenopathy = nontender, firm, rubber, nonsupperative, *bilateral*

Do *not* expect P. aeruginosa to be susceptible to

penicillin G/V ampicillin amoxicillin first generatino cephalosporins sulfa-trimethoprim furantoin

(TEST): Gram-negative zoonotic infections are rarely transmitted from human to human. Which one of the following is transmitted human to human?

pneumonic plague

Vector of B. Elizabethae

rats - entry of B. bacilliformis into human erythrocytes - periodic release into blood, entry into RBC, likely mechanism of recurrent fever - immune evasion

Warts in throat in HPV infection.

recurring *respiratory papillomatosis*

If a black color is seen in the but of a TSI culture, this indicates that the bacterium present can

reduce thiosulfate ions to produce hydrogen sulfide

In P. aeruginosa, neutrophils are ineffective at eradicating bacteria, and necrosis of neutrophils is caused by

rhamnolipid (surfactant - toxic to neutrophils)

What happens to cAMP as cell starves?

rises - cAMP = starvation signal in bacterial cells - glucose = favorite food = least machinery to digest --> glucose runs out = increased cAMP - *enzymes to digest amino acids only made when [cAMP] high* - virulence genes may also depend on cAMP & subject to catabolite repression