IDI Exam 2

Predisposing conditions for candidiasis

1) Antibacterial therapy (#1 cause of Candidiasis!) -Destroys normal flora balance allowing Candida to "take over" -Women can often develop vaginal candidiasis on antibacterial therapy 2) Indwelling devices (intravascular or urinary) 3) Altered immune status - e.g., HIV, diabetes, neutropenia 4) Abdominal and thoracic surgery 5) Immunosuppressive / cytotoxic therapy

Human anaplasmosis (HGE) symptoms

1-3 wks after tick bite - Flu-like symptoms Leukopenia, thrombocytopenia Rash only in 20% of cases Low mortality but hospitalization is common Immune response important but also damaging Note: PCR test are available for diagnosis, the visualization of morale is diagnostic but not very sensitive

Human monocytic ehrlichiosis symptoms

1-3 wks after tick bite - Flu-like symptoms Leukopenia, thrombocytopenia Rash only in 20% of cases Low mortality but hospitalization is common Immune response important but also damaging Note: PCR test are available for diagnosis, the visualization of morale is diagnostic but not very sensitive

Lymphogranuloma venereum (LGV) pathogenesis

1-4 week incubation Primary lesion at site of infection (penis, urethra, cervix, etc.) Lesion often overlooked (small, painless, inconspicuous) and heals rapidly Second stage is marked by swelling of draining lymph nodes, buboes (leading to rupture), some genital elephantiasis Can also from ulcerative proctitis in homosexual males

Examples of obligate intracellular bacteria

Anaplasma Chlamydia Coxiella (axenic growth in lab) Ehrlichia Orientia Rickettsia Bartonella (Special case- NOT obligate)

zoonoses (transmitted from animals): Larva Migrans

CLM =Cutaneous Larva Migrans -Migration through skin -Ancylostoma brasiliense (dog hookworm) -Ancylostoma caninum (dog Hookworm) VLM = Visceral Larva Migrans -Migration through viscera exclusive of skin -Toxocara canis (dog Ascaris) -Baylisascaris procyonis (raccoon Ascaris) -Anisakis simplex (Walrus, Seal Ascaris) OLM= Ocular Larva Migrans -Migration within the eye -Same as for VLM

Opportunistic pathogen

Cause disease only in a compromised host. The fungus Pneumocystis jirovecii easily infects people butrarely causes disease. It is, however, an opportunistic pathogen that causes life-threatening infections in AIDS patients whose immune system have been eroded by HIV

Lymphogranuloma venereum (LGV)

Caused by Chlamydia trachomatis L serotypes STI that is uncommon in U.S. (200-500 cases) Homosexual male reservoir High prevalence in Africa, Asia, South America More frequently diagnosed in males, usually asymptotic in women

Trachoma

Caused by Chlamydia trachomatis serotypes A/B/C Distributed world wide Major cause of preventable blindness of infectious origin (estimated that 500 million people are at risk of blindness with 8 million visually impaired) Infection restricted to humans Endemic in Middle East, North africa, India (It is endemic to areas with poor sanitation) Children have a high incidence and are chief reservoirs

Rickettsialpox

Caused by R. akari Disease seen in New York City homeless population Transmitted by mites (rodent, mite, transovarian, saliva) Rickettsialpox usually mild and self-limiting

Brill-Zinsser

Caused by Rickettsia prowazekii Recrudescent Milder disease most common in WWII immigrants to U.S

Rocky mountain spotted fever

Caused by Rickettsia rickettsii Most common rickettsial disease in U.S. Found mainly in southeastern atlantic/ south central 90% of cases are in April-Sept Average onset of 7 days Presents with Fever, chills, headache, myalgia, and rash after 3 days (sometimes no rash)

B. bacilliformis

Causes Carrion's Disease or Oroya Fever which is a series of infectious anemia found in peru, colombia, ecuador, etc Verruga peruana is the eruptive stage with vascular skin lesions These organisms invade RBCs Small gram negative rod

A. phagocytophilium

Causes Human anaplasmosis (human granulocytic ehrlichiosis- HGE) Found in Northern and central midwestern stats and northeast and central Atlantic states See usually from Mid-April to Late October

E. Chaffeenesis

Causes Human monocytic ehrlichiosis Found in the geographic distribution of lone star tick (Fort chafee, Arkansas; southeastern; south central; mid-atlantic; mid western) Have similar manifestations and resemble rocky mountain spotted fever

Orientia tsutsugamushi

Causes Scrub Typhus Found in South East Asia Similar in incubation and symptoms to other rickettsial diseases Rash found in 50%

B. quintana

Causes Trench fever Spread person to person by the human body louse, mostly homeless (IV drug use) Disease ranges from asymptomatic to severe. Debilitating (but no mortality), headache, fever, weakness, pain in long bones Some develop bacillary angiomatosis Potential role in culture negative endocarditis

Stages in the intracellular life cycle of Listeria monocytogenes

Cell entry Escape the vacuole Actin nucleation Actin-based motility Cell-to-cell spread

Host response to fungal infections

Cell mediated immunity is the main line of defense Usually, this response must be compromised for invasive fungal infections IN GENERAL: -Alveolar macrophages, inflammatory phagocytic cells are first line -TH1 induction is productive in clearance of fungi -TH2 modulation leads to susceptibility

Where is the site of cellular respiration in bacteria?

Cell membrane

Peptidoglycan is also known as:

Cell wall Murein

Treatment for Staphlococcus aureus rooted diseases/conditions

Cephalosporin combined with clindamycin Vancomycin (need a line in to administer)

What are one of the most common antibiotics?

Cephalosporins

Clinical presentation of malaria

Fever and flu like symptoms cold phase and host phase followed by drenching sweat suggest infection with vivax or ovale These symptoms can occur at intervals Uncomplicated disease may be associated with anemia and jaundice Severe disease is associated with seizures, mental confusion, kidney failure, acute respiratory disease syndrome, coma, and death Symptoms can develop as early as 7 days and as late as several months

Harms of fever

Fever can make patients uncomfortable. It is associated with increased metabolic rate, oxygen consumption, carbon dioxide production, and demands on the cardiovascular and pulmonary systems. Has been associated with impaired immunologic responses and cerebral injury

Classification of fungi: Sexual reproduction

Structures formed by fungi during mating are used to classify organisms and they inform: -How individual species respond to antifungal agents -The extent of invasive potential -Ecological niche (mode of transmission) Sexual form known as the "Teleomorph" 3 major types: Mucormycotina, Ascomycota, and Basidomycota

Chronic infection with Coxiella burnetii

Sub-acute endocarditis Affects prosthetic heart valve Poor prognosis

if AIDS is considered a pandemic, why isn't the common cold considered a pandemic?

The reason here is technical. Pandemics are caused by a single strain or closely related strains of a single microbe—for example, H1N1 influenza. Many different types of viruses and strains of viruses cause cold symptoms.

Carbon utilization in microorganisms

They must first phosphorylate glucose After a series of steps, pyruvate is formed Pyruvate can then be used to create ATP, NADH, NADPH depending on the pathway used

Properties of human flukes

They parasitize different locations They use one of two reproductive styles Flukes have both a tegument and a blind digestive gut Dx depends on location of adults Rx is same as for cestodes (in general) Life cycles are complex & involve multiple hosts

A 3-day-old female infant born by vaginal delivery after 39 weeks gestation was in good condition until fever and tachypnea developed on day 3. She also developed a staccato cough. Chest radiographs showed infiltrates over the whole lungs. Cultures of blood, urine, throat, feces, and CSF were negative. Antigen tests for C. trachomatis were positive from conjunctiva and nasopharyngeal swabs.

Infection with C. trachomatis D-K serotypes Should be treated with Erythromycin for 10-14 days

Host response to candidiasis

Innate immunity is most important for defense against hematogenous dissemination -Neutrophil is the most important component -Anti-Candida antibodies are produced, but their role in defense against the organism is unclear In the most serious form, Candida disseminates hematogenously and forms microabcesses in major organs -Probably enters bloodstream from mucosal surfaces where overgrowth has occurred -May enter from the skin

classes of transposable elements

Insertion sequences Transposons

Where must obligate intracellular bacteria grow?

Inside of eukaryotic host cells They cant grow on petri dishes, broth medium, etc.

How is Coxiella burnetii spread?

Most human infections associated with exposure to animals (animal placenta has high numbers) AIRBORNE EXPOSURE to dried organism (placenta, hides, etc.) Tick-vector important for spread in animals but not humans Worldwide distribution (animal handlers)

Chlamydophilia pneumoniae pathogenesis

Most infections are asymptomatic or mild, with no hospitalization Presents with persistent cough and general malaise Possible like with atherosclerosis and coronary artery disease Debate on prevalence

Treatment for candidemia

Most likely source of fungemia should be identified and treated -In a non-neutropenic patient, an intravascular catheter is the most likely source and removal of the catheter is often valuable -Other common sources: urinary tract and localized infections Antifungal agent should be employed -Amphotericin B or fluconazole for critically ill patients (never in combination therapy as they are antagonistic)

Zoonosis

Most of the zoonotic infections are difficult to diagnose Important to know the clinical syndromes associated with these pathogens to chose therapy wisely Antibiotic treatment is frequently empiric and based on level of suspicion Diagnosis is often confirmed days to weeks after treatment is given Important to consider risk factors for getting these infections

Direct microscopic exam (direct prep)

Most rapid, cost effective - often available STAT Rarely provides definitive morphology (often only a clue to the possible pathogen) Less sensitive than culture False negative and false positive results may occur May guide lab in most effective culture media

Transplacental transmission

Movement of a pathogen from an infected woman to her fetus across the placenta. Ex. A pregnant woman with syphilis caused by Treponema pallidum can transmit the organism to her fetus though the placenta

Properties of worms

Multicellular animals w/ discrete organ systems May or may not use multiple hosts Worms go through stages of development ( eg. L1-4, A) Length in humans varies from µm to 23 m long Transmission: GI, skin, vectors

Does the term infection imply every disease?

NO Any potential pathogen growing in or on a host is said to cause an infection, but that infection may be temporary if immune defenses kill the pathogen before noticeable disease results. Indeed, most infections go unnoticed

Are there an licensed vaccine for any human parasitic pathogen?

NO Note: 1 in 6 people worldwide suffer from some form of parasitic disease

Does salmonella species ferment sugars?

NO (they will appear yellow on the MacConkey)

Do Ehrlichia and Anaplasma have peptidoglycan and LPS?

NO!

Do fungi have any classic exotoxins?

NO!

Are obligate intracellular bacteria viruses?

NO! They are alive, have membranes, etc!

Mycobacterium tuberculosis

No Gram stain, Acid Fast stain Largest microbial cause of death world-wide Multi-drug resistant respiratory pathogen 'Waxy' cell wall structure is anti-phagocytic (they have a lipid rich cell wall structure. Note: they don't have a true cell wall)

Deuteromycota

No known sexual cycle -Not official class (obsolete) Referred to as "Fungi imperfecti" Aspergillus fumigatus -Most common invasive mould infection of man -Recently described sexual cycle

Does transposition of insertion sequences rely on homologous recombination?

No, and is termed illegitimate recombination

Does a bacterium simultaneously express all of the genes in its genome?

No, they coordinate the expression of genes Genes are transcribed into mRNA, which then is translated into proteins Transcription is used to produce rRNA species or tRNA molecules

Complications of C. trachomatis STI

Pelvic inflammatory disease (PID) May be silent causing chronic pain, infertility, ectopic pregnancy

Common therapy for S. pyogenes (Group A cocci) (gram positive)

Penicillin 2 million units iv every 4 hours or Cefazolin 2 grams iv every 8 hours If penicillin or cephalosporin allergic: vancomycin 1-2 grams iv every 12 hours

Common therapy for S. pneumoniae (gram positive cocci)

Penicillin-susceptible -Penicillin 1-2 milliion units every 4 hours iv Penicillin-resistant (increasing incidence) -3rd generation cephalosporin, Ceftriaxone 2 grams iv every 24 hours or quinolone class antibiotic -If penicillin or cephalosporin allergic: vancomycin 1-2 grams iv every 12 hours

When to avoid antibiotics

For bronchitis when pneumonia is not a concern watery diarrhea when dysentery or typhoid fever is not a concern delay use abasing otitis media for at least 48hr conducer nitrofurantoin instead of fluoroquinolone against uncomplicated cystitis reserve respiratory fluoroquinolones for unresponsive or high risk CAP patients avoid fixed dose combinations of antibiotics and anti-inflammatory or anti-histaminic drugs

parasitism

Form of symbiosis in which one organism (parasite) benefits at the expense of another organism usually of different species (host)

Staphylococcus aureus α toxin

Form pores in host cell membranes and cause leakage of cell constituents. It is a secreted effector protein It is a pore-forming toxin Also called α hemolysin which means it causes the lysis of red blood cells Note: once secreted in the environment, the recognize proteins on the host cell surface and form oligomers and will insert into the membrane forming a pore

Streptococcus pneumoniae

Gram positive cocci found as diplococci Encapsulated bacteria (immune evasion factor by preventing phagocytosis) Colonizes upper respiratory tract Associated with pneumonia, meningitis (adults), otitis media (children)

Enterococcus faecalis

Gram positive cocci found in clusters and short chains Group D Streptococci Normal flora of the colon Associated with urinary and cardiovascular infections

Corynebacterium diphtheriae

Gram positive rod which are "club-shaped", stained for metachromatic granules Non-spore-forming Causative agent of diphtheria Grey/white pseudomembranous exudate on the pharynx

Bacillus anthracis

Gram positive rods forming long chains Spore-forming organism, Multi-system pathogen Causative agent of Anthrax (cutaneous, inhalation, gastrointestinal) Anti-phagocytic capsule (composed of D-glutamate)

Clostridium/Clostridioides species

Gram positive rods which are large Anaerobic, spore-forming organisms Clostridium tetani --> Tetanus (toxin) Clostridium botulinum --> Botulism (food poisoning) Clostridium perfringens --> Gas gangrene and food poisoning Clostridioides difficile --> pseudomembranous colitis (GI infection)

Common drug allergies

Penicillins -may have cross allergy to cephalosporins and all Beta-lactam antibiotics Sulfa - may have cross allergy to all sulfa-containing antibiotics and other medications. Need to chose a different class of antibiotics whenever possible when there is a drug allergy. Also important to determine the type of allergic response the patient may have had. Some patients may have common side effects of the antibiotics but are not allergies.

Peptidoglycan is a mesh like structure the provides:

Rigidity and structure

Rod

Rod-shaped bacterium morphology

Allolactose (inducer molecule)

In the presence of lactose, this binds to LacI causing a conformational change in its structure This change in structure releases the allolactose-LacI complex from the operator thus alleviating repression and RNAP can initiate transcription of the lac operon

Where does Coxiella burnetii proliferate in humans?

In the respiratory tract and will then disseminate

Initial colonization

In utero, the fetus is protected from microbial colonization Post parturition the newborn infant begins to be colonized from: -Exposure to the mother's normal flora (GI, feces, etc) (debating which is better, vaginal --> or C section) -Exposure to the hospital staff -Feeding (breast milk or formula influence which types of microbes predominate)

Latent infection

Inactive infection (still lurking in the patient)

formites

Inanimate objects on which pathogens can be passed from one host to another (e.g. doorknob)

Meningitis

Infection of the meninges/ CSF

Cellulitis/myonecrosis/fasciitis

Infection of the skin, muscle, or fascia

secondary infection

Infection that follows a primary infection; damaged tissue (e.g., lung) is more susceptible to infection by a different organism Infection following viral influenza (Haemophilus influenzae)

iatrogenic infection

Infection transmitted from a physician to a patient Some septicemias (Staphylococcus aureus)

MacConkey agar

Selective for gram negative bacteria (contains bile salts and crystal violet that inhibit gram positive) Differentiates bacterial that ferment lactose, those that utilize lactose will decrease the pH and turn the agar reddish pink. Those not fermented by bacteria will be white (contains peptone as a carbon source so non-fermentors can still grow) E. coli- red Salmonella and shigella- white

MacConkey Sorbitol agar

Selective for the isolation and differentiation of E. coli O157:H7 (causes bloody diarrhea and a toxin it produces can cause hemolytic uremic syndrome) Lactose is replaced by sorbitol. Most E. coli ferment sorbitol and produce acid to grow red colonies E. coli O157:H7 cannot ferment sorbitol, so this strain uses peptone to grow and forms white colonies

Important sources of pathogens of HAI include

Self (exposure of the patient to own normal flora) Hospital staff ( S. aureus is found on the skin and in the nares of ~20-30% of people) Facility water sources (P. aeruginosa is commonly found in hopsital tap water, faucets, and sinks) and various others

Modes of Transmission associated with healthcare acquired infections (HAIs)

Self-infection Cross-infection Environmental infection

How would you determine the MBC?

Serial dilutions that would then be plated on plates with no extra antibiotics (cant just look at turbidity!) Those that grow no colonies would be the MBC

Diagnosis of R. rickettsii

Staining - Fluorescent antibodies- few labs Microimmunofluorescence (MIF)- Test sera for antibodies against various rickettsial antigens PCR becoming available Weil-Felix test- (no longer widely used) Cross reacting antibodies to Proteus species Note: prognosis is good if rocky mountain spotted fever is diagnosed early and treated properly

Clinical presentation of VLM

Typical patient is <5 yrs and heavily infected Presents w/ fever, hepato(spleno)megaly, lower respiratory symptoms, eosinophilia as high as 70% & hyperglobulinemia (IgM, G & E) Variable organ system involvement including: -Nephritis -Myocarditis -Various encephalopathies depending on #s and location Host response to T. canis is characterized by eosinophil-rich granulomas encapsulating migrating larvae (brain may be privileged site; little or no reaction) Pulmonary response includes bronchospasm, cough, wheezing, Löffler's pneumonia (transient snowy infiltrate by Xray)

bacterial variation

Variations within bacteria Ex. Streptococcus pneumonia capsule -Mucoid (smooth) (looks like snot) -Non mucoid (rough) (loose capsule)

Virulence factors of Escherchia coli

Varies with different strains! Pili Non-pili adhesins (intimin, Tir) Type III secretion systems Exotoxins: Shinga toxin, Cholera-like toxin (LT) LPS (endotoxin) K1 polysaccharide capsule

Bacillary angiomatosis

Vascular proliferative disorder seen primarily in immunocompromised (HIV/AIDS) Affects skin, subcutaneous tissues, and bones Seen in B. quintana and B. henselae infection

Must the patient comply to antibiotics?

YES, must complete the recommended course (compliance is only about 50%) 1-2 doses per day have better compliance injectable antibiotics are associated to premature discontinuation of treatments This lack of compliance can potential lead to resistance due to repeated exposure to sub-inhibitory concentration of antibiotics that foster the emergence of resistance

Do some fungi have some innate resistance to antifungals?

YES, some fungi are naturally less susceptible to Amphotericin B, Enchinocandins, Fluconazole, and Itraconzaole

Are fungi eukaryotes?

YES, they are closely related to animal and plant hosts Therefore they are more difficult to treat since they are closely related to us

Does sickle cell help against malaria?

YES, those with the hemoglobin AA genotype do SS also does, but they usually lead to earlier death

Do fungi have cell walls?

YES, which can be targeted for antifungals They contain: Glucan Chitin

Do our bodies harbor 100 trillion microbes?

YES- 10X more than human cells and 100 times more unique genes than human genome

Forms of fungal morphology

Yeast (single cells) Filamentous mould (starts are spore and begins to send out a tube in a polarized direction and becomes multicellular)

Is fever a protective mechanism to fight infection?

Yes, High body temperatures can help our immune system function better and can inhibit microbial growth. Children can generally tolerate a fever of 41°C (106°F), but for adults, 39.4°C (103°F) is about the safe limit. Above that temperature brain damage can occur.

Hyphae vs pseudohyphae

True hyphae comes from spore and just continues to grow in a polarized direction Pseudohyphae is really just a budding yeast with all the buds going in one direction

100 yrs ago major causes of death

Tuberculosis Pneumonia Gastrointestineal infections

Operon

Two or more genes encoded in tandem Ensures that protein subunits making up particular enzyme complexes or are required for a specific biological process are synthesized simultaneously and in the correct stoichiometry

Major groups of Rickettsia

Typhus group -R. prowazekii -R. typhi Spotted fever group -R. rickettsii -R. conorii -R. sibirica -R. akari

syndrome

a collection of signs and symptoms that occur together and signify a particular disease.

Suprapubic aspiration specimen

This method of urine collection has almost no risk of contaminating the sample if performed properly (considered a sterile collection procedure). It is preferred when the patient has urinary retention or for children less than 2 years of age. The needle insertion site is approximately 2 cm above the symphysis pubis. A needle is attached to a syringe and is inserted until the needle penetrates the anterior wall of the bladder.

Clinical presentation of OLM

Typical patient is 5 - 10 yr old and lightly infected -If not for visual impairment, infection would go un-noticed -None of the VLM syndrome elements are present Presents with unilateral vision impairment with or without strabismus Retinal granuloma formation can lead to blindness -Visualization similar to retinoblastoma -Anti-T. canis Abs in sera may be low or undetectable -Aqueous humor or vitreous fluid may be tested (ELISA) Other presentations incl. diffuse endophthalmitis, papillitis, secondary glaucoma

Conjugation

Transfer of genetic information that requires cell to cell contact (bacterial mating)

Transduction

Transfer of genetic information via a virus particle Involves the transfer of genetic material by infection with a bacteriophage Host DNA is erroneously packaged into the virus head resulting in a transducing particle Virus progeny carrying host DNA can introduce packaged host DNA into newly infected cells

Commensal protozoans are typically _______

avirulent

Epidemic Typhus

caused by Rickettsia prowazekii which is endocytosed and grows intracellularly Seen in times of war, famine, and poor hygiene Historically significant disease often killing many soldiers, etc. Rare in U.S.

neurocysticercosis

caused by an infection of the human central nervous system with an encysted larval form of the helminth Taenia solium seizures are common clinical presentation. Some have headaches, and less experience increased intracranial pressure, chronic meinigisit, encephalitis, vision loss, pain in nerve root distribution or sensory changes

Virulent protozoans often exploit ______

cell-specific adhesion molecules

_____ is the most consequential manifestation of severe falciparum infection

cerebral malaria caused by blockage of the cerebral capillaries with infected RBCs which adhere to the endothelium

DALY

disability adjusted life years Roughly the sum of year of life lost due to premature mortality and years lost due to disability for people living with a health condition or its consequences 1 DALY= 1 year of healthy life lost Note: in 2013 we experienced a total of 2.5 billion DALYs

Common therapy for francisella tularensis

doxycyline is drug of choice, quinolones have activity, problem in treating children and during pregnancy

Bacteria can use sugars as a carbon source for growth and prefer to use which sugar over the others?

glucose

When growing in an environment containing both glucose and lactose, bacteria such as E. coli preferentially metabolize __

glucose

Infections with L. monocytogenes follow___

ingestion of food It then indues its own internalization by cells that are not normally phagocytic. It does so via surface proteins called internalin

Sulfonamides

inhibit the folic acid synthesis needed for nucleic acid and protein synthesis Inhibits the synthase needed to create Dihydropteric acid Combination with Trimethoprim can be bactericidal

Trimethoprim

inhibits bacterial dihydrofolate reductase needed to generate Tetrahydrofolic acid and therefore folic acid metabolism Combination with Sulfonamides can be bactericidal

Cycloserine

inhibits formation of the D-ala-D-ala dipeptide precursor The net result is disruption of the cell wall synthesis, making bacteria susceptible to lysis by osmotic stress

Isoniazid

inhibits mycolic acid synthesis (occurs in mycobacterium)

pathogenicity

its ability to cause disease depends on a combination of the organism's genetic makeup, its location on the host's body, and the effectiveness of the host's immune response.

What underlying medical conditions increase the risk of serious infection and give careful examination of cause of fever

j cell Neutropenia

High creatinine indicates ___

kidney damage

Bactoprenol

lipid carrier molecule that transports peptidoglycan precursors across the cytoplasmic membrane Note: the structural unit is formed in the cytoplasm and this allows it to be transported out across the membrane

Monocistronic transcript

mRNA transcript that encodes only one protein

Polycistronic transcript

mRNA transcripts may also encode two or more proteins

The bacterial initiation complex comprises ___

mRNA, ribosome, and an initiator transfer RNA molecule (tRNA) carrying formylmethionine (fMet)

Are bacteria haploid or diploid?

haploid (usually only one copy of any given gene)

Dimorphic fungi

have both filamentous mold and yeast life-cycle stages At ambient (room temp) they are in saprobic phase with hyphae growing out At 37C they are in parasitic phase

Vehicle transmission

he disease agent is acquired by contact with fomites or through a medium such as water, food, or air

Covalescence

period after symptoms have disappeared and the patient begins to recover normal health

low quality antibiotics may result in___

pharmocokinetics profiles much different from the ones of original drugs which in turn may create increased periods of time of sub-inhibitory concentration exposure, leading to treatment failure and/or resistance. This is not a problem plaguing all generic drugs; many products have shown to be bioequivalent to original ones

Sterilization is accomplished using ____

physical, gas vapor, or chemical sterilants Objects should be clean --> reducing the bio burden (amount of foreign biological material) of an instrument before sterilization ensures optimal sterilization

What is the MOA of filters

physically removes bacteria and fungi

What color is gram positive?

purple

What host defense is crucial in the first 24h of infection with L. monocytogenes

neutrophils While innate immunity is sufficient to control infection, the acquired immune response is required for sterile immunity. Immunity is cell-mediated; antibody plays no measurable role. The critical effector cells are cytotoxic (CD8+) T cells that recognize and lyse infected cells, and the resulting extracellular bacteria are killed by circulating activated phagocytes

Invasiveness

refers to the ability of a bacterial pathogen to rapidly spread through tissue

reservoirs of infection

sites where pathogens are maintained as a source of infection

accidental host

one that can serve as a host, but is not the usual host in the parasites' life cycle ex. Humans or horses entering geographic areas harboring the disease (called endemic areas) can also be bitten by the mosquito.

endemic disease

one that is always present in a community and seen at a low rate. Often an animal reservoir harbors the organism.

Arthropod vectors

organisms that spread disease from one host to another Ticks, louse, fleas, mites

Downside of microbiota

Can trigger intestinal distress Source of infection Farts

World without antibiotics

Common infections are life threatening Major surgeries are problematic Pneumonia, UTI, and common general diseases are incurable Cancer chemotherapies are rare Population life expectancy is best at about 50

Trachoma pathogenesis

Complex pathogenesis Caused by serotype A,B,C Infection followed by secondary infection (another bacterial agent), inflammation of conjunctiva, scarring, eyelids turn-in, panes (invasion of vessels into cornea), eventual vision loss Clinical manifestations are caused by: -destruction of host cells -host inflammatory response

Bacterial ribosomes

Composed of rRNA and proteins which associate to form a 70S ribosome (50S + 30S) Note: RNA molecule catalyzes the formation of a peptide bond

Antibiotics can be classified as:

Concentration dependent: aminoglycosides, fluoroquinolnes, colistin and metronidazole Time dependent beta-lactams and most macrolide Note: this classification is useful in designing rational dosing schemes

Factors that affect the ability to eliminate contaminating microbes include:

Concentration or does of the killing agent Time of exposure Environmental conditions such as pH, temp, and presence of organic matter MOA of the killing agent Nature of the device/ instrument/ item being treated

malarial relapse

"the reappearance of parasitemia in sporozoites-induced infection, following adequate blood schizontocidal therapy". some remain latent as hypnozoites capable of delayed development and initiation of relapse. These must be destroyed to clear infection completely Note: seen in vivax and ovale

Life cycle of Leishmaniasis

- Nocturnal biting female SANDFLIES (Phlebotomus) are DEFINITIVE HOSTS - Sandflies ingest AMASTIGOTE-INFECTED macrophage from Human/mammal blood meal - AMASTIGOTE develops into PROMASTIGOTE inside the SANDFLIES which in turn is injected into a new host and becomes an AMASTIGOTE

Biochemical methods for fungal identification

-Limulus lysate assay detects 1,3-beta-glucan positive = presence of fungi...no specificity -Fungal metabolites -Serum D-arabinitol : positive for disseminated candidiasis

The probiotics in our gut are beneficial in the fact that they:

-Produce vitamins for host -Train the immune system -Prevent growth of pathogen -Regulate gut development

Diagnosis of Lymphogranuloma venereum (LGV)

1. Cytology, serology, and culture 2. Direct detection of antigen in clinical specimens via antibodies 3. Molecular probes, PCR, Direct Fluorescent antibody (DFA) slide test

Diagnosis of Trachoma

1. Cytology, serology, and culture 2. Direct detection of antigen in clinical specimens via antibodies 3. Molecular probes, PCR, Direct Fluorescent antibody (DFA) slide test

Main components of Peptidoglycan

1. N-acetyl Muramic Acid (NAM) 2. N-acetyl Glucosamine (NAG) 3. Pentapeptide (differs between bacteria; used for cross-linking)

5 interventions for controlling neglected tropical diseases

1. preventive chemotherapy 2. innovative disease management 3. vector control 4. veterinary public health 5. provision of water and sanitation

Properly collected clean-catch samples containing more than _____ colony forming units (CFU)/ mL of one type of bacteria generally indicate an infection, especially in a symptomatic patient.

10,000

Ehrlich

1st use of the term chemotherapy Compound 606-zSalvorsan

Plasmodial life cycle

2 stages: sexual and asexual asexual develops in humans, first the liver and then in circulating erythrocytes gametes for the sexual stage arise in the human and are taken up by mosquito, where the sexual stage will develop The exoeryhtrocytic phase -begins when female mosquito bites human and sporozoites are injected -these are cleared from circulation in 30-60 mins and reach liver parenchymal cells -in liver cells, they undergo asexual division where merozoites are formed The erythrocytic phase -merozoites are released from liver schizonts and invade RBCs -RBCs undergo rapid and marked deformation -parasite grows forming a ring-like early trophozoite -nourished by hemoglobin and produce pigment hemzoin -RBC ruptures and releases merozoites which invade other RBCs

What is the incubation period of syphilis?

2-6 weeks

Triplet code

3 bases in the mRNA sequence which corresponds to a codon for a specific amino acid

Chlamydiaceae life cycle is completed in _____ hrs

48-72 hrs

Throat culture

A STERILE cotton tipped applicator is briefly swabbed to the back of the throat near the uvula. Swab is placed in transport broth medium tube and sent to the lab. The laboratory will roll the swab onto Blood agar and then streak the plate for isolation (dilution streak). Throat culture is suitable for a patient with an inflamed sore throat. The bacterial pathogen that most often causes sore throat is Group A beta hemolytic streptococci (Streptococcus pyogenes). Viruses won't grow on this medium. Many normal microbiota can be found, however.

Abcesses

A collection of pus (dead neutrophils) in a cavity in any part of the body Associated with swelling and surrounding inflammation External (boils) Internal (various organs, e.g. appendicitis)

Nasopharyngeal swab

A nasopharyngeal swab is used to find and culture microbes in the nose and posterior nasopharynx. The most notable microbes detected here are bacteria of the Bordetella genus, the cause of Pertussis (Whooping cough). Procedure: Tilt the patient's head back gently and insert a swab into the posterior nasopharynx. If Bordetella is suspected, use a rayon or Dacron swab to allow for PCR testing of the bacteria. Gently rotate the swab against the nasopharynx for 20-30 seconds, allowing the bacteria to be absorbed. Place sample into a transport medium that allows for bacterial growth. Specimens will contain normal microbiota.

Infectious disease

A disease caused by a microorgan- ism (bacterial, viral, or parasitic) that can be transferred from one host to another

Disk Diffusion test

A disk or strip contains a known concentration of the antibiotic and the zone of inhibition is informative Larger zone of inhibition, the more potent Note: A small zone of inhibition doesn't necessarily mean the organism is resistant, if you can get enough drug into your patient to get to that effective concentration it might still work Note: A large zone of inhibition doesn't necessarily mean the organism is resistant, if the drug doesnt have good tissue penetration or bioavailability then it alters whether you consider that organism to be susceptible

Disease

A disruption of the normal structure or function of any body part, organ, or system that can be recognized by a characteristic set of symptoms and signs.

Bronchoalveolar lavage (BAL)

A fiber optic bronchoscope is passed through the mouth or nose into the lungs. The bronchoscope is wedged into a segmental bronchus (determined by radiographs), completely occluding the lumen. Saline is then injected into the wedged portion of the lung. A gentle suction is applied, collecting the lavage specimen into the collection trap for examination. These steps are repeated until there is an adequate specimen. Cytology, Gram staining and culturing are performed on the fluids collected. The lower portions of the lung are generally free of bacteria. However, BAL samples can be contaminated with normal flora from upper areas of lung.

Parenteral transmission

A form of horizontal transmission It is transmitted via a needle stick (often IV drugs)

Animal carcass transmission

A form of horizontal transmission It is transmitted via dead animals (e.g. tularemia)

Airborne transmission

A form of horizontal transmission It is transmitted via droplets (aerosols, sprays, spatters)

Oral-Fecal transmission

A form of horizontal transmission It is transmitted via fecal matter coming in to contact with oral cavity (e.g. Rotavirus)

Vector borne transmission

A form of horizontal transmission It is transmitted via mosquitoes, ticks, lice, mites, etc (often the progeny of these can carry the infection as well)

Indirect transmission

A form of horizontal transmission It is transmitted via person to object to person (can stay on object for long period of times)

Direct transmission

A form of horizontal transmission It is transmitted via person to person

Animal bite transmission

A form of horizontal transmission It is transmitted via saliva exposure (e.g. rabies)

Water, Food transmission

A form of horizontal transmission It is transmitted via these objects "church picnic potato salad" Often seen in Cholera outbreaks (bath in water and drink it like in Haiti)

Blood borne transmission

A form of horizontal transmission It is transmitted via transfusions (like HIV, etc. Not often now a days)

Spirochete

A long thin spiral shaped bacterial morphology

Virulence

A measure of the severity of disease Morbidity (how sick someone gets or how long they are treated for) vs. Mortality (death rate)

Peritoneal aspirate

A needle is used to drain fluid from the peritoneal cavity ( a normally sterile site). Peritoneal aspirate is often used as a means to diagnose an abdominal hemorrhage, metastatic cancer, and spontaneous bacterial peritonitis. The aspirate is analyzed to determine the presence of bacteria, blood cells, pH, and the gram stain of any bacteria present Cultures can be performed to determine the presence of bacteria or other infectious organisms.

Glycocalyx (capsules and slime layers)

A network of polysaccharide or protein that is secreted outside of bacteria Capsules are tightly attached to the bacteria and slime layers are loosely attached

Sequelae

A pathology that is the consequence of a previous disease/injury (ex. rheumatic fever)

Taenia solium life cycle

A person has an adult tapeworm in their intestine (definitive host) The feces will contain a proglottid which is full of eggs Eggs are within the environment and will be eaten by pigs (intermediate host) Oncospheres hatch, penetrate intestinal wall, and circular to musculature Oncosphere develops into cysticerci in pig muscle and we can consume undercooked pork and start the process over Note: we can serve as intermediate host by ingesting the eggs and can cause neurocysticercosis

CAP activator

A positive regulator in which the transcriptional initiation of the lac operon is dependent upon this Only activated when cAMP is bound When bacteria grow on glucose, cytoplasmic levels of cAMP are low, so CAP is not activated When glucose becomes depleted, cAMP concentrations increase resulting in the formation of activated cAMP-CAP complexes Activated complexes bind to the CAP operator significantly enchanting RNAP binding and transcription

Reservoir

A reservoir is an animal (such as a bird, rat, horse, or insect) that normally harbors the pathogen. For some pathogens, soil or water environments can be reservoirs

______ can encode a biochemical mechanisms that results in resistance to a class of antibiotics (e.g. macrolides, aminoglycosides, ß-lactams)

A single gene

_______ determines resistance to structurally unrelated antibiotics or efflux system

A single resistance gene

metastatic lesion

A site of infection resulting from dissemination Blastomycosis, fungal infection of the lung; can disseminate to form abscesses in the extremities (arms/legs)

Carrier

A special type of reservoir that is asymptomatic It is a person who harbors a potential disease agent but does not have disease.

Coccus

A spherical bacterium morphology.

Sputum sample

A sputum sample is taken when a lung or airway infection is suspected. Have the patient rinse his or her mouth to remove food particles and debris. Then have the patient breathe deeply and cough several times to achieve a deep specimen. A Gram stain will be performed the same day the sputum sample is collected. The presence of bacteria and white blood cells indicates an infection. The samples are typically cultured on sheep blood agar, chocolate agar, and MacConkey agar.

Is there a connection between microbiota and obesity?

A study showed obese individuals having much higher numbers of the H2-utilizing methanogenic Archaea compared to normal-weight or post-gastric-bypass individuals

latent infection

A type of infection that may occur after an acute episode; the organism is present but symptoms are not; after a time, the disease can reappear Cold sores due to herpes virus

Microbe

An organism that is so small that, normally, cannot be seen without the use of a microscope Viruses, prions, bacteria, fungi, protozoa, and some algae are all included in this category

Bacterioidies phenotype

Anaerobic growth (most gut flora)

Competent bacteria

Able to take up DNA fragments from related species across their cell walls These fragments may be present in the environment of the competent cell as a result of lysis of other organisms Once taken up in the cell, the DNA must recombine with a homologus segment of the recipient's chromosome to be stably maintained and inherited If the DNA is unrelated, the absence of homology prevents recombination and the DNA is degraded

Cholera toxin is an ______

A:B toxin

Diphtheriae Toxin is an ____

A:B toxin (has A and B subunit)

Candidiasis spp. virulence factors

Ability to grow at 37°C. Ability to adhere to host tissues The yeast-to-hyphal transition ("phenotypic switching") *The change from blastospore to pseudohyphal and hyphal stages is generally considered integral to the organism's penetration into host tissue

Diseases/Conditions caused by Staphylococcus aureus

Abscesses (boils) Impetigo Toxic shock syndrome Scalded skin syndrome Food poisoning Osteomyelitis (common in diabetics) Endocarditis Pneumonia

Healthcare-associated infection (HAI)

Acquired during the course of treatment for other conditions within a healthcare setting (nosocomial infection) Caused by a wide array for infectious agents including bacteria, fungi, and viruses originating from: -Endogeonous sources -Exogenoous sources

Immunity for malaria

Acquired immunity - Complete immunity not achieved - Partial immunity develops over time Hemoglobin disorders Protective genetic factors to severe malaria

____ mediates nucleation of host actin filaments to propel the listeria intra- and intercellularly

ActA which is a surface protein It mimics host proteins of the Wiskott-Aldrich syndrome protein (WASP) family

Quinolones

Active against Gram- negative bacteria Broad spectrum (Pseudomonas aeruginosa, Methicillin-resistant Staphylococcus) Inhibits DNA gyrase

Treatment for Coxiella burnetii

Acute: Doxycycline Chronic: Doxycycline + Rifampin + Fluoroquinolone Note: vaccine available (not U.S.) for animals and humans but problems associated with use

T. cruzi infection clinical manifestations

Acute: fever, swelling at bite Chronic can take years to develop: -cardiac > GI disease -Heart failure -Esophageal/colonic dysmotility

Schistosoma Lifecycle

Adult worms within humans which are shedding eggs in the feces or urine depending on the species The eggs reach a body of water and they hatch to release miracidia Miracidia penetrate snail tissue Sporocysts develop in snail (successive generations) Free swimming cercariae released from snail into the water Cercariae infects humans through the skin where they will become schistosomulae They enter circulation and migrate to portal blood in the liver and mature into adults

Serology and biochemical markers used for identification of fungal infection

Additional tests are often needed: -Culture is not revealing -Fungus is very slow growing -Carb assimilation results are ambiguous -Clinical situation is acute Serologic, Biochemical and/or genetic tests often run in parallel

Normal Body temp

Adult ,mean body temp is generally 37.2C in the morning and 37.7C overall. It varies with age time of the day, level of activity, and phase of the menstrual cycle infant and young children generally have higher temps (due to higher surface area to body weight ratio and higher metabolic rate) mean is around 37.5-38C Note: there can be a variation in time of day (~0.5C), if sick it can range between (1C)

Properties of human tapeworms

Adult tapeworms inhabit the GI lumen Adult Morphology: -Head called scolex -Body called a strobila consisting of proglottids (segments) Cestodes are hermaphrodites -Each proglottid contains both male and female organs; they can but don't -Both proglottids and free eggs are passed in feces (Dx is by stool exam for O&P) Outer surface covered by a tegument Lack a true digestive system -Nutrients actively transported across tegument Rx is generally Niclosamide, stops worm's defense against being digested Note: some of these within the family are a neglected parasitic infection

aerial vs. vegetative hyphae

Aerial hyphae go up into the air vegetative hyphae grow in the substrate

midstream (clean catch) specimen

After urine has flowed for several seconds, a sterile container is placed in the stream and about 60 mL of "midstream" urine should be collected without stopping the flow.

Common host factors for susceptibility to "opportunistic" fungal pathogens

Age (low birthweight-premature infant; elderly) Burns Chronic respiratory disease (COPD) Debilitating illness (HIV/AIDS) Endocrine disorders (diabetes) Intensive care w/ parenteral nutrition Surgery Traumatic injury

Biofilms

Aggregates of bacteria that adhere to each other on a surface (e.g. plaque) Phagocytes and antibiotics have trouble penetrating these

occupation effect on infection susceptibility

Agricultural workers may be exposed to anthrax spores, nearly ubiquitous in soil, as well as the agent of Q fever (Coxiella burnetii), present in the placenta of infected pregnant cattle. Hunters can contract zoonotic diseases such as tularemia and plague. People who work with animal hides, which may carry anthrax spores, can occasion- ally contract anthrax, although this is rare. And, of course, prostitutes (male or female) expose themselves to a host of sexually transmitted agents.

What are some common misuses of antibiotics

Agroindustry and veterinary practice

MOA of EtO

Alkylation-induced damage of proteins/nucleic acids

Malaria is transmitted by:

All species are transmitted by the bite of an infective female Anopheles mosquito. Occasionally, transmission occurs by blood transfusion, organ transplantation, needle sharing, or congenitally from mother to fetu

Terbinifin

Allylamine Blocks ergosterol synthesis by inhibiting squalene epoxidase given orally to treat dermatophyte infections

Immune status and immunopathogenesis effect on infection susceptibility

Although the public typically thinks that bacterial, viral, and fungal pathogens directly cause the signs and symptoms of a disease, this often is not the case. Most of the damage caused by an infection is actually due to the immune response meant to rid usof the invader. Various white blood cells can become quite aggressive when attacking an infection and can cause a considerable amount of collateral damage to healthy host tissues (immunopathology). So the better a host's immune system is, the faster it can rid the host of infection, but the more damage can occur in the process.

Major drugs used for antifungal therapy

Amphotericin B (lipid formulations) Fluconazole Intraconazole Voriconzaole Posaconazole Caspofungin Micafungin Anidulafungin Note: these are agents for primary therapy of invasive infections

Treatment of L. monocytogenes infection

Ampicillin is the drug of choice Adults should receive IV ampicillin at high dose Many recommend gentamicin for synergy, but it may not help Dosages must be reduced for patients with renal insufficiency Cephalosporins are not effective and should not be used. Neonates should receive ampicillin and gentamicin at doses based on weight

Fever

An abnormal elevation of body temperature that occurs as part of a specific biologic response that is mediated and controlled by the central nervous system infants 0-30 days (>38C) 3-36 months (> 38 to 39C) adults (> 37.8 to 39.4C)

Hyperthermia

An abnormal elevation of body temperature that occurs without a change in the thermoregulatory set point in the hypothalamus. This failure of normal homeostasis results in heat production that exceeds the body's capacity for dissipation. Body temperature in patients with hyperthermia does not respond to antipyretic agents. Characteristic clinical features of hyperthermia include a history of environmental heat exposure or use of drugs that interfere with normal thermoregulation (eg, anticholinergics); hot, dry skin; and central nervous system dysfunction (eg, delirium, convulsions, coma). Hyperthermia can be rapidly fatal; adverse physiologic effects begin to occur at temperatures >41°C (105.8°F)

ß-lactamase

Any of a group of enzymes produced by bacteria that catalyze the chemical opening of the crucial beta-lactam ring structures in beta-lactam antibiotics

Relative toxicity of antibiotics

Antibacterials < Antifungals < Antiparasites < Antiviral Note: antivirals are most toxic because viruses really a lot on host for replication, so things inhibiting replication of virus also kills the host cell

Serologic methods for fungal identification

Antibody titers: -Analyze sample for patient antibody to pathogen -Increase in titers can be indicative of active infection -EIA and ID Fungal antigen detection: -Direct detection of pathogen and disease activity -Serial antigen/antibody titers to monitor progression -Usually detect polysaccharide antigen of fungus -LA, EIA and direct fluorescent-antibody tests

Pathogen

Any bacteria, virus, fungus, protozoan, or worm (helmet) that causes disease

Classes of protozoan parasites

Apicomplexa Kinetoplastida Ameboza Metmonada

Primary pathogens

Are disease-causing microbes with the means to breach the defenses of a healthy host. For example, the rod-shaped (bacillus) Shigella flexneri, the cause of bacillary dysentery, is a primary pathogen. Wheningested, it can survive the naturaldefensive barrier of an acidic stomach, enter the intestine, and begin toreplicate.

Tertiary syphilis

Arise if secondary syphilis is untreated Neurological Cardiovascular Granulomatous lesions- Gummas- painless- autoimmune (T cell mediated hypersensitivity) Note: this can lead to destruction of any organ in the body

Secondary syphilis

Arises if primary syphilis went untreated Systemic Flu-like symptoms (fever, cough, sore throat, stuffy nose, muscle aches, headache, fatigue) Lymphadenopathy Lesions- over entire body, palms, and soles (contain like spirochetes) Usually last 2-6 weeks Can go latent - Asymptomatic for months or >30y -25% can go back to secondary symptoms -33% spontaneously cured

Age effect on infection susceptibility

As a general rule, the people most susceptible to an infec- tion are either very young (under 3 years old) or very old (over 60 years old). The very young and very old are more susceptible largely because of the natural development of our immune system. Immune systems are still developing in newborns and babies and are waning in the elderly. As a result, these two populations have a harder time fending off infections than do healthy children or adults under 60

Infective propagules are typically made during:

Asexual reproduction This is the anamorphic stage in which infective particles (conidia or spores) are made This stage is the common form isolated in the clinical lab

Steps of biofilm formation

Attachment monolayer Microcolonies EPS production Mature biofilm Dissolution and dispersal

Axillary thermometry

Axillary temperature is consistently lower than rectal temperature, but the absolute difference varies too widely for a standard conversion. Axillary temperatures may be measured in neutropenic patients who are unable to use an oral thermometer.

___ is the drug of choice for Legionnaires disease

Azithromycin

Treatment for Trachoma

Azithromycin, Doxycycline, Erythromycin

Amphotericin

Azole Broad spectrum Forms complexes with ergosterol which alters membrane fluidity and forms pores leading to leaky membranes Fungicidial Most effective for severe mycoses Must be given IV Serious SE particularly to renal toxicity

Stool sample

Bacterial pathogens are common causes of diarrhea and can be identified by culturing stool samples. Collect the stool sample (solid or liquid) in a clean, sterile container. Do not include urine. The stool sample should be taken to the lab within an hour after collection. The lab will streak a small amount of the stool sample onto various culture media and incubate at 37OC (body temperature) for 24 hours.The media typically used are MacConkey Agar, Hektoen, Sorbitol MacConkey, and Campylobacter Agar.

Are aminoglycosides bactericidal or bacteriostatic

Bactericidal Because they irreversibly bind and cause defective proteins!

glycopeptide class

Bactericidal, cell wall synthesis inhibitor Vancomycin for gram+ infections. -Primarily used for methacillin-resistant staphylococcal infections -Is frequently used for other gram positive infections in patients with allergies to the Beta-lactam class of antibiotics

Rifampin, rifamycin, rifampicin class

Bactericidal. RNA synthesis inhibitors Rifampin: has gram+ activity but used mostly for treating mycobacterial infections (tuberculosis) but fortunately it has activity against some atypical, zoonotic infections - Always used in combination, never as single drug therapy because resistance develops very easily.

Quinolone class

Bacteriocidal, DNA synthesis inhibitors Ciprofloxacin: gram- activity>>gram+ activity Levofloxacin: gram- activity but also good streptococcal activity Problem: contraindicated in children (<8 yr old) and in pregnancy.

Lifecycle of Toxoplasma

Cats pass feces infected with oocysts This can infect animals or sandboxes Theses make it to humans where tissue cysts in form in the skeletal muscle, myocardium, brain, and eyes Note: blood transfusion and through the placenta is another way that humans can be infected

beta lactam class

Bacteriocidal, cell wall synthesis inhibitors Penicillins: gram + and -,prob with resistance, still useful for many streptococci, spirochetes Nafcillin: gram+ activity, primarily used for methacillin susceptible Staphylococcus aureus Cephalosporins: gram + and gram -, commonly used and effective, low toxicity and side effects 1st generation: cefazolin, has gram+ & gram- activity but used mostly for common gram+ infections 3rd generation: ceftriaxone, has gram- & gram+ activity. Uniquely crosses blood brain barrier very well and used for most cased of meningitis. Carbapenems: gram + and gram-, very broad spectrum, mostly used for antibiotic resistant pathogens

Lipopetide class

Bacteriocidal, depolarizes bacterial membrane potential Daptomycin for gram+ infections only -Reserved mostly for methacillin resistant Staphylococcus aureus infections, alternative to vancomycin. Also used for antibiotic resistant gram+ infections

Are those antibiotics that target protein synthesis bactericidal or bacteriostatic

Bacteriostatic Except for aminoglycosides

Tetracycline class

Bacteriostatic, protein synthesis inhibitor Doxycycline: mostly used for atypical pathogens ( most are intracellular pathogens). Although bacteriostatic it is very effective against these organisms. Problem: contraindicated in children (<8) and in pregnancy!

Aminioglycoside class

Bacteriostatic, protein synthesis inhibitors Gentamicin: has gram+ and gram- activity. -Used mostly for synergy in combination with the beta-lactam class antimicrobials. Usually reserved for serious infections with staphylococcal and gram negative sepsis and/or for antibiotic resistant pathogens. Problem: nephrotoxicity and ototoxicity can be severe and disabling. Only used cautiously and when necessary.

Sulfonamides class

Bacteriostatic. Folic acid synthesis inhibitors• Sulfonamides have gram+ and gram- activity, good staphylococcal activity (but not for serious infections). Also has activity against some zoonotic infections.

B. henselae

B. henselae : Bacillary angiomatosis (esp. HIV) involving skin, lymph nodes or liver and spleen. Resembles Kaposi's sarcoma Role in subacute endocarditis (like B. quintana) Cat-scratch disease (lymphadenopathy at draining lymph node), self-limiting, > 20K cases Associated with cat scratches, bites, contact with fleas

How are bacteria and viruses separated?

Bacteria (>0.22µ) typically are larger than viruses (<0.22µ), therefore if a filter is placed with size of 0.22µ, only the viruses will pass

3 basic parts of flagella

Basal body Hook Filament

Chloramphenicol

Binds reversibly to 50S Prevents peptide bond formation Broad spectrum Toxic effect- Aplastic anemia

Candidiasis epidemiology

Because they are human commensals, the source of infection is usually endogenous Although Candida infections have been recorded since antiquity, infections have become more common due to modern therapeutics Candida is now among the most common nosocomial pathogens

Fluconzaole

Best penetration of CNS Used fro cryptococcal and coccidiodial meningitis

Subacute infection

Between acute and chronic, as in "subacute endocarditis"

What are 2 very important bacteria to GI health?

Bifidobacterium Lactobacillus acidophilus Conditions like irritable bowel syndrome (IBS) may be due to changes in the resident flora that leads to increased inflammation. This can be corrects with probiotics like yogurt, cheese, etc These are both Gram positive bacteria

What microbiota is found in the intestines of breast fed babies?

Bifidobacterium (easily digests human milk products)

polyenes

Bind to ergosterol to form pores Ex. Amphotericin B and Nystatin

Vegetative hyphae produces what during anamorphic stage?

Blastoconidida Chlamydoconidia Arthroconidia

Allylamines

Blocks ergosterol synthesis by inhibiting squalene epoxidase given orally to treat dermatophyte infections ex. Terbinafine

Septicemia

Blood infection, origin usually from other infections (e.g. urosepsis)

Enterohemorrhagic strains (EHEC)

Bloody Diarrhea, Pedestals, Shiga toxin --> Hemolytic Uremic syndrome

Enteroinvasive strains (EIEC)

Bloody diarrhea, facultative intracellular pathogen

Temperature homeostasis

Body temperature is controlled by the thermoregulatory center of the hypothalamus. The thermoregulatory center balances heat production, derived primarily from metabolic activity in muscle and the liver, with heat dissipation from the skin and lungs. The thermoregulatory center is able to maintain a fairly steady body temperature in normal temperature environments. However, at environmental temperatures higher than approximately 35°C (95°F), the body's ability to dissipate heat is overwhelmed, and core temperature rises

Rash pattern of typhus

Body to periphery

Tetracyclines

Broad spectrum antibiotic binding to the 30S subunit and inhibiting protein synthesis Primarily employed as an alternative drug Often used against Rickettsia and Chlamydia because they get into eukaryotic cells really well in a high enough concentration to kill Note: many bacteria actively transport tetracycline

Lower respiratory tract infection

Bronchitis Pneumonia Note: this is a mucosal infection

3rd generation cephalosporins

Broad spectrum (Gram positive, Gram negative, Pseudomonas)

_______ is the most common etiologic agent of Candidiasis

C. albicans However, the use of effective antifungal therapies has caused a shift towards non-albicans infections -Non-albicans species now account for almost half of all Candida blood infections (candidemia) This change is clinically important as the various species differ in susceptibility to antifungal agents

Members from the genus chlamydophila

C. pneumoniae C. psittaci note: these were formerly under the single genus of chlamydia

Members from the genus chlamydia

C. trachomatis

Facultative Intracellular pathogens

Can grow outside cells or can invade them and grow inside (they have virulence factors that cause them to be uptaken by host cells) Can be cultured on artificial media Salmonella enterica, Shigella Francisella Note: the line between extracellular and facultative intracellular is blurring

Neurocysticercosis

Can vary from asymptomatic infection to severe disease and death. - Signs and symptoms of NCC usually non-specific - Severity is indicative of infection characteristics (size, number and location of cysts): Parenchymal NCC: i) epileptic seizures (~80% of NCC patients) Acute symptomatic seizures or "chronic epilepsy" with calcified lesions ii) Recurrent or chronic tension-type headache Extra-Parenchymal NCC: Cysticerci may reside in the ventricular system or the subarachnoid space and a life-threatening intracranial hypertension may develop

Opportunistic mycoses common risk factors

Cancer therapy (corticosteroids) Organ transplantation Primary immune deficiency (chronic granulomatous disease) HIV (emerging) Diabetes (emerging) COPD (emerging)

What is the most common pathogen to man?

Candida is the 4th most common blood-isolate -i.e., common fungal infection of the circulatory system! Candida is a small, thin-walled, ovoid yeast -Measures 4-6 µm in diameter -Reproduces via budding Candida species generally occur in 3 forms in tissue: -Blastospores -Pseudohyphae -Hyphae

Mechanisms to Reduce Antibiotic Resistance

Control, reduce, and cycle antibiotic usage Improve hygiene in hospitals and among hospital personnel and reduce movement of patients to reduce dissemination of resistant organisms. Generate new antibiotics Modify existing antibiotics to produce agents inert to known bacterial resistance mechanisms Maintain adequate drug levels (take full course) Elimination of antimicrobial agents from animal feeds

What are some mechanisms extracellular pathogens use to thwart host immune cell phagocytes

Capsules Biofilms Extracellular toxins Phase variation- they can also periodically change the structure of their surface proteins to confuse the immune system

Treatment for Bartonella

Cat-scratch disease (self-limiting) does not appear to respond to antimicrobial therapy All others: Doxycycline, Erythromycin, Azithromycin, Rifampin

Catalase test

Catalase is an enzyme that converts hydrogen peroxide (H2O2) to water and oxygen. Some bacteria produce the catalase enzyme, and some do not. This test is often used to differentiate Streptococci (do not have catalase enzyme) and Staphylococci bacteria (catalase positive). To perform the catalase test: 1. Isolate the bacterial colony of interest and apply to a glass slide. 2. Apply a hydrogen peroxide reagent to the bacteria on the glass slide. 3. A positive test will show the formation of gas bubbles upon the application of the hydrogen peroxide. A negative test will show no reaction.

Major types of HAIs include:

Catheter associated urinary tract infections (CAUTIs) Surgical site infections (SSIs) Ventilator-associated pneumonia (VAP) Central line-associated bloodstream infections (CLABSIs) Clostridium difficile infection (CDI) Methicillin-resistant Staphylococcus aureus (MRSA)

3 important classes of worms that infect humans

Cestodes: Tapeworms (ribbon-like, very flat) Trematodes: Flukes (leaf shaped and fleshy) Nematodes: roundworm

57 year-old woman presented with new exertional dyspnea and lower extremity swelling. An echocardiogram revealed dilated cardiomyopathy and reduced ejection fraction.

Chaga's disease

Mechanisms of resistance to azoles

Changes to target enzyme Overexpression of target enzyme Increased efflux of drug

Pityriasis versicolor

Child displays pigmented, irregular macules on the trunk Direct prep= positive for hyphae and yeast with KOH/Calcofluor Spaghetti and meatballs Culture: negative after 14 days at 25C

How do microbes develop these resistance mechanisms?

Chromosomal mutations: -For example, alteration of ribosomal protein to give streptomycin resistance -Can be on step, high level resistance or multistep low level increases -Single species, Single parent Inheritance -Plays a large role -Multi resistance transfer -Inter species transfer

Do parasitic infections tend to be acute or chronic?

Chronic, there are often no symptoms until months or years after exposure Exception: malaria

Treatment for infection with B. bacilliformis

Ciprofloxicin Doxycycline Ampicillin Sulfamethoxizole/Trimethoprim

Endocervical swab

Collects cellular debris from the anterior surface of the cervix (external os) to detect pathogenic organisms, typically Chlamydia trachomatis and Neisseria gonorrhoeae. To collect a sample, the cervix is visualized using a speculum (no lubricant). A sterile swab is used to remove mucus and other secretions then a new swab is inserted into the external os and rotated 360 degrees. This sample is to be placed in Stuart's transport medium (liquid) for transfer to the lab to test for gonorrhea. A new swab of the os is taken and placed in a solution for liquid cytology to test for Chlamydia (Chlamydia, although they are bacteria, are not visible in a Gram Stain). The samples should be submitted to the lab in less than 24 hours. The specimen will contain normal microbiota.

Iodophors

Combinations of iodine and a solubilizing agent to provide sustained release of iodine Used as skin antiseptic

Candidiasis clinical aspects

Clinical Manifestations: -Severity is largely dependent on immune status of host -In right setting - can cause disease in any organ system 3 major groups of candidiasis 1. Mucocutaneous candidiasis -Cutaneous lesions - skin, nails, intertrigenous areas -Mucous membrane infections - thrush, vaginitis, balanitis -Chronic mucocutaneous candidiasis (CMCC) 2. Candidemia 3. Deeply invasive candidiasis -Disseminated form affects lungs, kidneys, heart, spleen and others...

Diagnosis of fungal infections

Clinical laboratory must ID fungal pathogen Prompt diagnosis requires clinical suspicion based on knowledge of fungal disease and risk factors Physicians Exam should include: -Physical diagnosis (signs and symptoms such as rashes, etc.) -Recent travel history -Past history of travel and residence -Occupation -Recreation -Other medical conditions

Virulence factors of Staphylococcus aureus

Coagulase encases bacteria in host fibrin to protect itself from the immune response Leukocidins kill phagocytes (e.g. Panton-valentine leukocidin, PVL)

Does Penicillium aerial hyphae produce conidia or spores?

Conidia

Aerial hyphae produces what during anamorphic stage?

Conidiphores -production of conidia -organisms have septate hyphae -many different morphologies Sporangiophores -production of spores -organisms have aseptate hyphae -many different morphologies

Ocular infections

Conjuctivitis Trachoma Note: the eye is thought to be mostly an immune privileged site

Hfr strains

Conjugative plasmids such as the F plasmid of E. coli can integrate into the bacterial genome These stains mediate high frequency transfer and recombination of genomic DNA

Conjugation and antibiotic resistance

Conjugative transfer of plasmids with resistance genes has been an important cause of the spread of resistance to commonly used antibiotics within and between many bacterial species, since no recombination is required for expression in the recipient.

Reiter's syndrome (reactive arthritis)

Conjunctivitis, urethritis, and poly arthritis initiated by C. trachomatis genital infection Also can be caused by Campylobacter, Yersinia, or Salmonella Most prevalent in young white men "Cant see, Cant pee, Cant climb a tree"

Uropathogenic E. Coli (UPEC)

Contain P type pilli that helps them adhere and remain and cause infection in the Urogenital tract

Blood agar plate

Contains 5-10% mammalian blood and is an enriched differential media used to isolate fastidious organisms and detect hemolytic activity (some produce hemolysins and can lyse RBCs) Beta-hemolytic bacteria produce complete lysis of RBCs surrounding the colony (clear, straw- colored halos appear). Example is Streptococcus pyogenes. Alpha-hemolytic bacteria (sometimes called partial lysis) will produce greening of the agar around and under the colony. Ex. Streptococcus mutans or bovis. The bacteria generate excessive amounts of H2O2 that react with hemoglobin in the RBCs to produce a green breakdown product. Non-hemolytic (previously called gamma-hemolysis) is the term referring to lack of hemolytic activity. There is no hemolysis and, therefore, no change in the medium.

Colistin Nalidixic Acid Agar (CNA)

Contains the antibiotics colistin and naladixic acid which inhibit the growth of Gram negative organisms. Gram positive organisms grow on this medium.

Differential growth media

Contains various substrates and pH indicators to indicate presence/absence of certain chemical reactions; organisms not prevented from growing. Commonly used to identify organisms that break down a particular substrate.

Flucytosine

Converted by cytosine deaminase to 5-flurodeoxyribocyclic acid monophosphate which interferes with thymidylate synthesis and DNA and RNA synthesis Mammalian cells lack cytosine deaminase Actively transported into fungal cells Used with Amphotericin B to treat crypto coccus or candidiasis Ex. 5-fluorocytosine

23 year old returning traveler with pain on right foot, returning from thailand

Cutaneous larva migrans

Daptomycin

Cyclic lipopeptide First member of a new class of antibiotics MOA is disntic form any other approved antibiotic Rapidly kills Gram positive bacteria by disrupting multiple aspects of bacterial membrane function Emergence of resistance is rare Note: they are not effective against Gram negative because the outer membrane prevents them from gaining access

Urinary Tract infection

Cystitis Pyelonephritis Prostatitis Urethritis Note: this is a mucosal infection

Gram negative membrane composition

Cytoplasm Inner membrane Thin peptidoglycan layer Outer membrane Outer membrane has an inner leaflet (phosphotidylethanolamine) and a complex outer leaflet composed of Lipopolysaccharide (LPS)

Gram positive membrane composition

Cytoplasm Cytoplasmic membrane with proteins in it Thick extensively cross-linked peptidoglycan Also contain: Lipoteichoic acid (LTA) and Teichoic Acid are in the peptidoglycan Note: together, LTA and Teichonic acid form a PAMP recognized by TLR2

Appropriate use of antimicrobials

Cost effective use of antimicrobials which maximizes clinical therapeutic effect while minimizing both drug-related toxicity and the development of antimicrobial resistance

Fungal cell wall: Glucan

D-glucose monomers with glycosidic bonds 2 types: 1. ß-(1,3)-glucan (form major parts) 2. ß-(1,6)-glucan (mostly in the periphery) Most express a SINGLE ß-(1,3)-glucan synthase protein (which makes some antifugnal drugs effective)

Treatment for Rickettsialpox

Doxycycline

Treatment for Scrub typhus

Doxycycline No vaccine and should avoid mites

Treatment for Rickettsia prowazekii infection (epidemic typhus)

Doxycycline and other tetracyclines Control louse populations in epidemics; hygiene A vaccine has been used but has virulent flaw (reverts back to virulent form)

Bacterial DNA is transcribed into mRNA by ____

DNA dependent RNA polymerase (RNAP)

Transposable elements

DNA sequences that can jump (transpose) form a site in one DNA molecule to another in a cell (but they DONT autonomously replicate) While plasmid transfer involves the movement of genetic information between bacterial cells, transposition is the movement of such information between DNA molecules. For example: -chromosome to plasmid -plasmid to plasmid -plasmid to chromosome

Cholestasis

Decreased bile which can cause malabsorption of fats Can be caused by bile obstruction or defects in the synthesis of bile in the liver May find conjugated bile in serum as a sign of cholestasis

How are parasites diagnosed?

Diagnosis is based on Site Specificity (often where reproduction is occurring) Parasites inhabiting GI System -Stool Exam for Ova & Parasites (O&P) ~Negatives should be repeated at least 2 more days ~O&Ps won't detect parasites that don't reproduce in gut Parasites inhabiting the blood or lymph - Thick & Thin smears, Knott's concentration, EIA PCR & EIA are good but not yet universal Ask your patient, "Where have you been and when were you there?"

Diagnosis and treatment of malaria

Diagnosis: direct identification -Thick smear: sensitivity -Thin smear: species Most treatments act at blood phase -Chloroquine, mefloquine, quinine, artemisinins, atovaquone/proguanil Latent phase of P. vivax/P. ovale -Treat with primaquine

A 67-year-old woman presents to her physician complaining of persistent diarrhea with weight loss, bloating, and excess flatulence (passing gas). She also mentioned her stools looked 'greasy', which the physician knew as a sign that ingested fat was not being absorbed. A blood test revealed the woman's B12 level was abnormally low. Cultures of fecal specimens failed to detect any typical bacterial pathogens that could cause diarrhea. What is going on?

Decreased vitamin B12 level and excess fat in the stool suggested the woman had a malabsorption disease. Possible cause --> small intestine bacterial overgrowth disease Confirmed by aspirating fluid from the jejunum and finding abnormally high numbers of facultative and anaerobic bacteria such as Streptococcus, E. coli, Lactobacillus and Bacteroides. Fermentation by these organisms produced the bloating and flatulence. Antibiotic treatment corrected the syndrome (by stoping the overgrowth).

Disinfection

Define as the use of physical procedures or chemical agents to destroy most microbial forms, except bacterial spores, on inanimate objects Note: the main difference between sterilant and disinfected activity is determined by the time in concentration which the killing agent is used

Antisepsis

Defined as the use of chemical agents on skin or other living tissue to inhibit or illuminate microbes; no sporicidal action is implied

Sterilization

Defined as the use of physical procedures or chemical agents to destroy or eliminate all forms of microbial life including bacterial spores Note: the main difference between sterilant and disinfected activity is determined by the time in concentration which the killing agent is used

Lab diagnosis of fungal infections

Definitive diagnosis of the pathogen allows for best treatment and clinical support Diagnosis is made through direct examination of clinical specimens, histopathology, and culture Identification made by: Morphology Biochemisty Genetics Serology

What is the MOA of heat

Denaturation of proteins

Treatment for Escherchia coli rooted diseases/conditions

Depends on severity of disease Diarrhea, usually no antibiotic treatment UTI (Bactrim, quinolone) Meningitis (Cephalosporin (ceftriaxone which is only given IV))

Subcutaneous mycoses

Dermis, muscle, fascia Present as lesions, but rarely invade deep tissue Chronic and insidious Ex: Lymphocutaneous sporotrichosis -Sporothrix schenckii -Thermal dimorph, traumatic inoculation

Human microbiome

Describes the commensal microbes/normal flora that inhabits the human body e.g. skin, nose, mouth, stomach, intestines, GI tract are all colonized by a wide variety of microbes from all 3 domains (or superkingdom) of life (bacteria, archaea, eucarya) They are a mixture of aerobes and anaerobes

Gene expression

Describes the process involved in decoding the genetic information contained within a gene to produce a functional protein or RNA molecule

Chloramphenicol mechanisms of resistance

Detoxification by acetylation of hydroxyl groups

Penicillins and Cephalosporins mechanisms of resistance

Detoxification by hydrolysis of ß-lactam ring by ß-lactamase enzyme. PBPs that do not bind the penicillins

Larva Migrans diagnosis and treatment

Diagnosis H & P -Eosinophilia -Enlarged Liver and/or Spleen -Pneumonitis -Geophagic Pica Serological Testing -Toxocara-specific ELISA ~Serum (primary test) ~Aqueous Humor (OLM) Treatment Albendazole or Mebendazole Prevention -Vet care for pets -Police pet droppings -Cover sand boxes

Case History 3: A 29-year-old, previously healthy woman presented with bloody diarrhea and abdominal pain. Her urine output was scant and darker than normal. Her hemoglobin level was 7 g/dL (normal 12-16). BP 120/70; respiration 32/min (normal is 12-20/min); temp 98F; serum creatinine 4.2 mg/dL (normal 0.6- 1.2). Her platelet count was 19,000/ml (normal 150,000 to 300,000). A diagnosis of Hemolytic uremic syndrome (HUS) was made based on the occurrence of acute renal failure, hemolytic anemia, and thrombocytopenia. Her husband informed the attending physician that he and his wife had eaten steak tartare at a fancy restaurant a couple of days ago.

Diarrhea/gastroenteritis caused by Escherchia coli

Pathogen immune avoidance

Different pathogens possess unique tools to avoid the immune system. Some periodically change the molecular shape of their surfaces to confuse the immune system; Salmonella does this. Others, such as Staphylococcus aureus, secrete molecules that "tell" immune system cells that "all is well, no infection here." Still others (Shigella, for instance) secrete proteins that convince immune system cells to kill themselves in a process known as apoptosis

Chlamydophilia pneumoniae diagnosis

Difficult since these organisms are very restricted and difficult to culture They will not grown on C. trachomatis host cell lines (so can't just diagnosis by culture) Must use PCR, or post-facto diagnosis by serology Note: this is not really life threatening infection

Two types of contact transmission

Direct (when microorganisms are transferred from one infected person to another) Indirect (when microorganisms are transferred through a contaminated intermediate object or person)

Genetic methods for fungal identification

Direct detection by DNA amplification and PCR sequencing

How is staphylococcus transmitted?

Direct or indirect contact

Leishmania spp. (21 species infect humans) (Leishmaniasis)

Disease: -Cutaneous: incubation:f 1-4 wks; small bump or ulcer; not painful; often self-resolves -Muco-cutaneous -Visceral (=Kalazar): incubation period: Months; can remain latent (like TB!); symptoms: fever, malaise; Exam: splenomegaly, hepatomegaly; Labs: pancytopenia. Important opportunistic infection in areas where it coexists with HIV. Diagnostic: Tissue biopsy; serology; PCR for species identification Transmission: sandfly Treatment: Pentavalent antimonials, liposomal amphotericin B, miltefosine

Toxoplasma gondii (toxoplasmosis)

Disease: -Normal hosts: mild disease -Ocular toxoplasmosis: retinitis -CNS: encephalitis, especially concerning immunocompromised (HIV) patients --> Ring-enhancing brain lesions -Congenital infection (Hydrocephalus/intracranial calcification/chorioretinitis) Distribution: 1/3 of the world population is estimated to be infected with Toxo Diagnostic: Direct identification: Tissue biopsy Serologic testing IgM for primary infection; IgG for reactivation Transmission: Ingestion of infected or contaminated food/water - Oocysts in soil from cat feces -Raw/undercooked meat -Transplacentally -Tissue cysts remain latent reactivation during immunosuppression Treatment: Pyrimethamine & Sulfadiazine (inhibitors of folic acid synthesis)

Entameoba histolytica and E. dispar (amebiasis)

Disease: Bloody diarrhea (acute) Liver abscess (12 wks later) Non-invasive disease: trophozoites contained to the intestinal lumen. --> diarrhea Trophozoites can invade the intestinal mucosa (intestinal disease; amebic colitis), or blood vessels, reaching extraintestinal sites such as the liver, brain, and lungs (extraintestinal disease; amebic abscesses). Distribution: developing countries, world travelers, returning migrants, immunocompromised population Diagnostic: Stool O & P, serology Transmission: Oral-fecal route; ingestion of contaminated water and/or food Treatment: metronidazole Note: GI protozoa

Trypanosoma brucei gambiensi and rhodosiensi (African trypanosomiasis)

Disease: Also known as "sleeping sickness" Clinical signs: -Headache and stiff neck -Sleep disturbances -Depression -Seizures, tremors, comma Distribution: sub-Saharan Africa Diagnostic: -History of being in endemic area and bitten by a Tsetse fly (and the chancre) -Definitive Dx: Finding tryps in blood or CSF or lymph node aspirate -High IgM levels Transmission: bite by tse-tse fly (genus Glossina) Treatment: Pentamidin, suramin, melarsoprol, eflornithine, and nifurtimox

Cryptosproidium parvum and C. hominis (cryptosporidiosis)

Disease: Watery diarrhea (acute). Incubation period of ~ 7 days. Immunocompromised patients may have more severe complications, such as life-threatening malabsorption and wasting. Distribution: Worldwide, warm climates Diagnostic: Stool O & P, antigen Transmission: Oral-fecal route, contaminated water (swimming pools, water playgrounds, unpasteurized drinks) Treatment: metronidazole, antiretroviral therapy (in HIV patients) Note: GI protozoa

How can MIC be determined?

Disk Diffusion Test Dilution test

Variation

Divergence in qualities of an organism or biotype from those typical or unusual to its group

Staph A. : MacConkey

Doest grow!

Treatment for Lymphogranuloma venereum (LGV)

Doxycycline or Tetracycline for 21 days

Common therapy for Brucella species

Doxycycline plus rifampin are combination of choice. Quinolones also have activty. For children and pregnancy the sulfonamides plus rifampin are used.

Ehrlichia and Anaplasma treatment

Doxycycline, Rifampin if needed (pregnancy) Other antibiotics are not effective Vaccine not available Avoid tick infested areas, use repellent, wear protective clothing, remove ticks as soon as possible

Treatment for R. rickettsii

Doxycycline, Tetracycline Note: ß lactams are NOT effective even though these have a cell wall No vaccine, so diagnosis is key

Passive Diffusion

Driven by concentration gradient Water and gases No proteins needed

Sulfonamides/Trimethoprim mechanisms of resistance

Drug resistant replacement enzyme (ex. Dihydrofolate reductase)

How is C. trachomatis STI transmitted?

During vaginal, anal, or oral sex (anything that has friction and can cause micro abrasions that give them access to the cells under the protective epithelium, or anything that gives them direct access to a mucosal surface) Can also be transmitted from an infected mother to baby during childbirth

Fungi Kingdom

Estimated 1.5 million species -Most are strict aerobes -Saprophytes, parasites, commensals Global impact: -Food production (Beer, bread, cheese, citric acid) -Pharmaceutical production (Penicillin, statins, cyclosporin) -Models for research (Heterologous protein expression, cell and developmental biology)

Alcohols

Ethyl and isopropyl alcohols are most effective as 60-90% solutions in water common ingredient in hand sanitizers

Gas Vapor sterilants

Ethylene oxide (EtO) -Most used method for sterilization of temp/moisture sensitive items -readily penetrates paper, cloth, plastic H2O2 -Advanatage of a short exposure time, but less effective than EtO Plasma gas -High heat vaporization H2O2 converts to plasma gas -An efficient sterilant with low toxic byproducts

Bacteria vs eukaryote structure

Eukaryotes - Complex with organelles - 10 - 100 µm - Cholesterol containing Prokaryotes - Low complexity with no compartments or organelles - Internal filament network that provides structure (akin to actin) - 1 - 10 µm - Have flagellum - Have plasmids - Have cell membrane

7 major characteristics of fungi

Eukaryotic cell Cell wall Cell membrane Growth morphology Hyphae (filaments) Colonies Forms of propagules (spores or conidia)

Gram-negative phenotype

Membrane-Wall-Membrane Note: based on staining and microscopy

4th generation cephalosporins

Extended spectrum (can kill a lot of thing!) This helps because you dont necessarily have to know the exact bug causing disease, this drug will cover many of the possible causative agents

How is trachoma transmitted?

Eye-to-eye --> droplets, hands, clothing, contaminated flies

Conjugation is dependent upon the _____

F plasmid or F factor (F=Fertility)

Do bacteria have histones?

No (have histone-like proteins)

Peptidoglycan (DAP-PG) from gut bacteria circulates and stimulates ___

Neutrophils These help to prime/enhance killing capacity

What microbiota is found in the intestines of formula fed babies?

Enterobacteriaceae Streptococci Staphylococci

What are some exotoxins produced by Staphylococcus aureus

Enterotoxin (ingested, causes vomiting within 4 hours) Toxic Shock syndrome toxin (body rash, fever, lowered blood pressure) (this is a superantigen) Exfoliation toxin (cleaves desmoglein)

Erythromycin/Lincomycin mechanisms of resistance

Enzymatic modification (methylation) of 23S ribosomal RNA

How do infectious agents gain access to the body

Each organism is adapted to enter the body in different ways. Food-borne pathogens (for example, Salmonella, E. coli, Shigella, and rotavirus) are ingested by mouth and ultimately colonize the intestine. They have an oral portal of entry (oral route). Airborne organisms, in contrast, infect through the respiratory tract (respiratory route). Some microbes enter through the conjunctiva of the eye, others through the mucosal surfaces of the genital and urinary tracts (urogenital route). A gents that are transmitted by mosquitoes or other insects enter their human hosts via the parenteral route, meaning injection into the bloodstream. Wounds and nee- dle punctures can also serve as portals of entry for many microbes. Shared needle use between drug addicts has been a major factor in the spread of HIV. Denying a pathogen access to its portal of entry is an effective way to halt the spread of disease

Gram negative transglycosylation

Each structural unit is attached via a ß1-4 linkage and containing a pentapeptide This creates a linear polymer

Common therapy for Borrelia burgdorferi

Early infection: penicillins or doxycycline Late infections: intravenous ceftriaxone or penicillins

What is the human defense against helminths?

Effective response: IgE and eosinophils. T-cell release of IL-4, IL-5 and IL-13. Eosinophilia is non-specific -Allergic, autoimmune, and neoplasia

Human response to protozoan parasites

Effective response: cell-mediated immunity Evades immune system: -Hide inside cells (malaria, Leishmania, T. cruzi) -Change surface coat (trypanosomes)

Aminoglycosides mechanisms of resistance

Enzymatic modification of drug: (adenylation, phosphorylation, acetylation)

What forms do Ehrlichia and Anaplasma exist in?

Elementary bodies Reticulate bodies

What are the two forms seen within the Chlamydiaceae lifecycle

Elementary body (EB) Reticulate body (RB)

_______ with contributing history may indicate parasitic infection

Elevated eosinophilia

Empiric antibiotic therapy

Empiric broad-spectrum antibiotics are indicated for severe infections. Usually requires 1 or more different classes of antibiotics to treat the common pathogens responsible for the infection. Some combinations may be synergistic, most are merely additive. However, it is not a standard of care to treat every known pathogen you can think of. This would require too many drugs with too many toxicities and it would be more likely to seriously harm a patient than it would be to treat an extremely rare pathogen. Note: use this when a treatment is needed immediately but you need a lab culture for diagnosis

Crytococcus spp.

Encapsulated, budding yeast - environmental C. neoformans var. gattii may be emerging primary pathogen

Transmission of Chaga disease

Endemic areas: T. cruzi is transmitted by 3 species of blood-sucking triatomine insects (kissing bugs) (Triatoma infestans, Rhodnius prolixus, Triatoma dimidiata ) Alternative Routes of Transmission: -Congenital (Mother-to-child): transmission rate of 4.7% ~ Maternal parasitaemia is the main biological determinant ~Sustained exposure to the vector is associated with decreased parasitaemia and congenital transmission (induces a Th1 immune response that overcomes the less effective pregnancy-induced Th2 polarisation). Blood and blood products: -Transmission rates: ~10-25% per infected blood unit ~After solid organ transplantation from an infected donor: Recipients: 0-19% kidney ;0-29% liver;75-100% heart Contaminated food and drink (Oral)

Most intracellular bacteria enter host cells by___

Endocytosis or induced phagocytosis

Major groups of parasites

Endoparasites: live inside the host -Intracellular:protozoan parasites -Extracellular: worms, protozoan parasites Ectoparasites: Live outside the host -Arachnids: ticks, mites -Insects: fleas, lices

Fungi produce ___

Ergosterol, not cholesterol, which is a major sterol in the fungal membrane This is found in the plasma membrane Therefore, this is a major target for antifungal drugs

_____ is the drug of choice for Mycoplasma pneumoniae

Erythromycin

Chlamydophilia pneumoniae treatment

Erythromycin, Azithromycin, or Tetracyclines Note: control is difficult because these organisms are ubiquitous

Lab diagnosis of Candidiasis

Established via visualization of pseudohyphae or hyphae on direct prep: -KOH prep (with calcofluor white) -Gram's stain -Periodic Acid-Schiff (PAS) stain -Gimori Methenamine Silver (GMS) stain of infalmmed tissue Will see sausage shaped pseudohyphae and true hyphae with septa

Histoplasmosis

Ex. 10 yo girl went spelunking and develops flu like symptoms with persistent fever. They acquire a bronchial alveolar lavage specimen with results: Giesma stain: positive for many intracellular yeast Culture: positive for mold after 2 wks at 25C, will not form defining morphologic structures Serology: hybridization protection assay detects rRNA from culture clinical isolate using a specific DNA probe

Blastomycosis

Ex. 17 yo male from indiana presents with symptoms of pneumonia and a hacking cough producing yellow sputum. They acquire a bronchial alveolar lavage specimen with results: Giesma stain: positive for broad based, budding yeast Culture: positive for mold after 6 wks at 25C on SABHI, thermal conversion positive 2 weeks later Serology: complement fixation (CF) test positive for blactomyces surface antigen

Candidiasis

Ex. 32 year-old HIV-positive, diabetic male receives IV fluids for 72 hrs during a hospital stay. He develops fever and diffuse rash on trunk. The IV catheter was removed and a small gelatinous mass found at tip Culture on SDA and SDA-CC yields entire colonies Pure isolate cultured to CHROMagar, green colonies after 2 days Germ tube test

Complex growth media

Exact chemical makeup unknown. Ex. brain heart infusion media. This is ground up hearts and brains, and we dont exactly know the chemical makeup of these

Tetanus Toxin

Exotoxin produced by Clostridium tetani Spores are introduced into a wound, germinate, and release this toxin which affects skeletal muscle Causes spastic paralysis resulting in convulsive contractions of voluntary muscles and eventually spasms that affect respiration and therefore death via suffocation It is a two component toxin that works via: The toxin moves from the periphery to CNS neurons It then inhibits exocytosis of the neurotransmitter GABA (inhibitory) This results in no dampening of ACH release

Staphylococcus aureus Exfolative toxin

Exotoxin that results in Scalded Skin Syndrome It cleaves Desmoglein 1 causing the epithelia top layer of skin to fall off You can have a focal infection on place and the toxin disseminates throughout the circulation

2nd generation cephalosporins

Expanded spectrum (Higher resistance to ß-lactamase)

Pathogenicity

Factors related to a microbes ability to cause disease (ability to avoid the immune system)

Are salmonella facultative or obligate intracellular pathogens?

Facultative They enter host cells by induced phagocytosis and resides within a modified phagolysosome Note: they use Type III secretion apparatuses to inject effectors they are like the proteins we use to rearrange actin. This causes a folding of the membrane and therefore the phagocytosis of the pathogen

Clinical signs and symptoms of malaria

Febrile illness Severe manifestations -Cerebral malaria (seizure, confusion) -Renal failure ("black water fever") -Severe anemia -Placental malaria Asymptomatic: adults in endemic populations

How do we become infected by parasites

Fecal-Oral (Soil-Transmitted) Amebiasis Ascariasis Trichiuriasis Food-borne Trichinellosis Taeniasis Vector-borne Malaria -- mosquitos Leishmaniasis - sandflies Filariasis - Mosquito, Black Flies Trypanosomiasis - Triatomid bugs, Tsetse Flies Skin-penetrators Ancyclostomiasis (Hookworms) Schistosomiaisis

How is Escherchia coli transmitted

Fecal-oral route

Anticipatory guidance for fever

Fever is not an illness but a physiologic response. In otherwise healthy children, most fevers are self-limited and benign, provided that the cause is known and fluid loss is replaced; fever does not cause brain damage. If there are signs of serious illness, a health care provider should be consulted. There is no evidence that fever makes the illness worse. Initial measures to reduce the child's temperature include provision of extra fluids and reduced activity. Fever may merit treatment with an antipyretic agent if the child is uncomfortable Decreased temperature after receiving an antipyretic agent does not help to determine whether the child has a bacterial or viral infection. Children who are receiving treatment for fever do not need to be awakened to receive the antipyretic agent. Children who are receiving antipyretic medications should not be given combination cough and cold preparations Antipyretic medications should be dosed according to weight, rather than age. Instructions for safe storage of antipyretic medications.

Fever pathogenesis

Fever is the result of a highly coordinated series of events that begins peripherally with the synthesis and release of interleukin (IL)-1, IL-6, tumor necrosis factor, interferon-alpha, and other endogenous pyrogenic cytokines by phagocytic cells in the blood or tissues. These cytokines enter the blood and are carried to the anterior hypothalamus, where they induce an abrupt increase in the synthesis of prostaglandins, especially prostaglandin E2 (PGE2). The induction of PGE2 in the brain raises the hypothalamic set-point for body temperature. After the set-point is raised, the thermoregulatory center recognizes current body temperature to be too low and initiates a series of events to raise body temperature to the new set-point. This involves augmentation of heat production by increased metabolic rate and increased muscle tone and activity, and decreased heat loss through diminished perfusion of the skin. Body temperature rises until a new equilibrium is achieved at the elevated set-point. The upper limit of temperature due to fever appears to be 42°C (107.6°F), but it is unusual for temperature to exceed 41°C (106°F) without some element of concomitant hyperthermia. In addition to causing fever, pyrogenic cytokines increase the synthesis of acute-phase proteins by the liver, decrease serum iron and zinc levels, provoke leukocytosis, and accelerate skeletal muscle proteolysis. IL-1 also induces slow-wave sleep, perhaps explaining the somnolence frequently associated with febrile illnesses. The increase in peripheral PGE2 may account for the myalgias and arthralgias that often accompany fever. Increased heart rate is a normal physiologic response to fever.

What are some host structure exploited by bacteria for attachment?

Fibronectin Glycoproteins Integrins Cell surface carbohydrates

Case History 1: One Saturday afternoon and evening, the local hospital started receiving patients complaining of severe vomiting, stomach cramps and diarrhea. In all, the hospital treated 25 people with similar symptoms. Patient histories revealed that all had attended a picnic that day thrown by the local Church and all patients report eating a potato salad that had sat outside all afternoon. Vomitus was not bloody and within 6 hours the symptoms resolved.

Food poisoning. Not an infection, but an intoxication. Staphylococcus aureus contaminates food and secretes exotoxins which are heat stable. When toxin is ingested it stimulates the vagus nerve and produces vomiting

Intraconazole

First choice for histoplasmosis and blastomycosis

Tigecycline (Tygacil)

First glycylcycline antibiotic to gain FDA approval Analog of tetracycline Bacteriostatic inhibitor of protein synthesis IV administered drug that is active abasing a variety of gram negative and gram positive pathogens including MRSA Approved by FDA in 2005

Chlamydophilia pneumoniae

First isolated in Taiwan (TW-183); related to another isolate (AR-39) = TWAR A human intracellular pathogen, transmitted by aerosol droplets Symptoms resemble other atypical pneumonias, bronchitis, sinusitis

Epidemic Typhus symptoms

Flu like symptoms (fever, chills, headache, myalgia) Average 8 day onset Rash (not always) No Eschar

Exogenous DNA can either be ___

Fragments or intact plasmids This can be taken up into the cell by different mechanisms The fate of the DNA could be: -Fragments must recombine into another DNA molecular (chromosome or plasmid) -Plasmids can, but do not need to recombine -DNA can be degraded

Vertical transmission

From mother to child via placenta, transit though vaginal canal, or breast milk

Griseofulvin

Fungistatic agent that affects fungal microtubules inhibiting DNA replication and mitosis Note: nucleic acid synthesis as an antimicrobial target

innate resistance against P. falciparum

G6P dehydrogenase deficiency ß thalassemia ovalocytosis

Where is Escherchia coli normally found

GI tracts of humans and animals Note: there are good and bad strains

Escherichia coli

Gram negative rods Multi-system pathogen Normal flora vs. food/water-borne introduction (virulence factors can cause them to be pathogenic) Causes UTI, neonatal meningitis, sepsis, diarrheal disease

Gastrointestinal infection

Gastritis (gastric ulcers, duodenal ulcers) Enteritis Gastroenteritis Colitis Enterocolitis Colicysitis (gallbladder) Note: this is a mucosal infection

Complications of R. rickettsii infection

Gastrointestinal symptoms Respiratory failure Encephalitis Renal failure Note: it depends on what organ is infected!

substandard antibiotics

Generic drugs that do not meet the requirements of bioequivalence

bacterial chromosome

Genetic information carried in this long, double stranded circular molecule of DNA Constitue a continus coding sequence of genes

Plasmids

Genetic information in bacteria that are extrachromosomal and present in small circular DNA molecules

Virulence factors

Genetic traits that enhance a microbe's ability to cause disease

Host genotype effect on infection susceptibility

Genetics not only determines whether we have blue or brown eyes but can also influence our susceptibility to infectious diseases. The host receptors to which bacteria and viruses bind are all encoded by host genes. Losing or altering a host receptor will affect susceptibility to a given pathogen.

____ prevents the expression of the lac operon, the products of which transport and metabolize lactose

Glucose metabolism

EM of Gram + membrane and Gram - membrane

Gram + have a very thick peptidoglycan layer compared to the Gram - The cytoplasmic membrane is the same and is a bilayer on the inside Gram - have a second lipid bilayer called the outer membrane that surrounds the peptidoglycan

Staphylococcus Aureus

Gram Positive Cocci found in clusters One of the most common causes of human infections Multi-system pathogen Part of nasal and skin flora Found in abscesses, endocarditis, pneumonia, sepsis, food poisoning

Bordetella pertussis

Gram negative Rod which causes whopping cough They cause whopping cough by pertussis toxins causing damage

Bacteroides thetaiotaomicron

Gram negative anaerobe found in the lower GI system Digests complex carbs (therefore they are probiotic microbes) 15-20% of our caloric intake (thanks to these bacteria breaking down things we cant)

Neisseria meningitidis and Neisseria gonorrhoeae

Gram negative cocci that form diplococci (kidney bean shaped) Meningitis (Nm) Gonorrhoeae (Ng, gonococcus) Fastidious organisms (difficult to grow must use chocolate agar)

Vibrio species

Gram negative curved rod Vibrio cholera --> Cholera (voluminous watery diarrhea) Vibrio parahaemolyticus--> seafood-borne diarrhea Vibrio vulnificus --> seafood-borne diarrhea, cellulitis, sepsis

Salmonella species

Gram negative rod Associated with enterocolitis (GI), Typhoid fever, sepsis Ingestion of contaminated food/water-borne Intracellular pathogen (resides in a phagocytic vacuole)

Clostridioides difficile

Gram positive, spore forming anaerobe C. diff is often a part of the normal intestinal microflora Antibiotic treatment, especially following surgery, kills off normal intestinal microflora, leaving C. diff to grow unabated (there is new real-estate available for it to grow and create an imbalance) C. diff --> toxin --> damages and kills host epithelial cells --> exudative plaques form on the intestinal wall (these plaques are diagnostic) The small plaques eventually coalesce to form a large pseudomembrane that can slough off into the intestinal contents

Streptococcus pyogenes

Gram postive cocci found in chains Group A Streptococci (GAS) Multi-system pathogen Leading bacterial cause of pharyngitis and cellulitis Also causes rheumatic fever and acute glomerulonephritis (AGN)

Common therapy for E. coli (gram negative rod)

Gram-negative septicemia (extraintestinal) -1st or 3rd generation cephalosporins are commonly used, eg., ceftriaxone 2 grams iv every 24 hours. -Concern about increased resistance developing and may need a broader spectrum antibiotics or combination therapies -May need very broad spectrum antibiotics such as the carbapenem class of iv therapy -May need to use with gentamicin for synergy

Septic shock

High fever, low BP, can be due to infection or circulating toxins Note: septicemia can process to septic shock leading to end organ failure Note: often due to TNF-α

Extracellular pathogens

Grow outside of host cells Can be cultured on artificial media Staphylococcus aureus, Streptococcus pyogenes Note: the line between extracellular and facultative intracellular is blurring

HIV is not an airborne infectious agent, so why is AIDS a pandemic?

HIV does not rapidly kill its host, and because the virus tampers with the immune system, the host does not kill the virus. Thus, over a person's life, ample opportunity exists to transmit the virus to a partner, especially considering that the symptoms of AIDS can take years to appear. During this extended prodromal period, the virus is present in an assortment of body fluids and is easily transmitted by various sexual practices. The sexual mores of today combined with rapid air travel and an inability to cure victims has led to the rapid spread of the virus around the globe.

Claude, an 18-year-old University student, came to the county urgent-care clinic with a low-grade fever, malaise, and headache. He was sent home with a diagnosis of influenza. He again sought treatment seven days later after he discovered a macular rash (flat, red) developing on his trunk, arms, palms of his hands, and soles of his feet. Further questioning of the patient revealed that one year ago, he had a painless ulcer on his penis that healed spontaneously.

Had the exudate from the ulcer been examined one year ago, you could see microbes moving in a corkscrew fashion This is from Treponema palladium subspecies pallidum-syphilis Note: key for diagnosis is dark field microscopy

Neonatal Menigitis strains of E. Coli

Have K1 polysaccharide capsule that inhibits their phagocytosis and have the ability to cross the BBB

Blood culture

Healthy contains no microbes In general, samples are collected directly into aerobic and anaerobic bottles that are subsequently incubated at 35C. Standard procedure is to obtain 3 samples: aerobic and anaerobic samples from one site (one arm), and a second aerobic sample from a second site. If the patient is on antibiotics, then a resin bottle will be substituted for the aerobic one. The resin binds any free antibiotic in blood to prevent it from killing bacteria present in the sample. Two to three sets of 3 samples may be ordered, as one culture is rarely sufficient for diagnosis. The sample should be sent to the lab immediately, and should never be refrigerated. In addition to culture samples, order a complete blood count (CBC) if a bacterial infection is suspected to look at leukocyte (Neutrophils or PMNs) levels. Culture bottles are incubated for up to 5 days to detect bacterial growth. If two or more bottles are positive for the same bacteria, it is likely a true positive. If only one bottle grows, it may be due to a skin contaminant (usually Staphylococcus epidermidis). With a positive test, a Gram Stain is performed to get a general idea of the bacteria present, and then subcultures are run on agar plates to identify the specific bacteria.

L. monocytogenes infection prevention

Healthy persons should take standard precautions to prevent food-borne illness: fully cooking meats, washing fresh vegetables, carefully cleaning utensils, and avoiding unpasteurized dairy products. In addition, persons at risk for listeriosis, including pregnant women, should avoid soft cheeses (although hard cheeses and yogurt are not problematic) and should avoid or thoroughly reheat ready-to-eat and delicatessen foods, even though the absolute risk they pose is relatively low.

2020 major causes of death

Heart disease Cancer Stroke

Physical sterilants

Heat- The most common sterilization method used in hospitals, efficacy depends on time and temp of exposure -Autoclaves generate moist heat using high pressure steam sterilization (121C, 15 lb/sq in pressure at least 15 mins) -Ovens generate dry heat to keep air temperature high for long periods of time (170C for 1 hr or 160C for 2 hr) Filtration -HEPA filters --> airborne particles -0.2 µm pore size filer --> liquids Ionizing radiation (gamma rays, X-rays) --> items that cannot be treated by heat or other chemicals UV radiation --> used to decontaminate rooms, biosafety cabinets

Mannitol salts agar

High concentration of NaCl (7.5-10%), mannitol, and phenol red Selective for Staphylococcus (other gram positive and gram negatives won't grow) S. aureus ferments mannitol and produces acid that changes the medium from red to yellow S. epidermis, doesnt ferment mannitol so the medium stays red

Waksman

Streptomycin isolated Streptomyces griseus Applied the term antibiotic 1st randomized control trial

Enviroment of Duodenum/Jejunum

High pH (8-10) Bile salts 10^7 CFUs per gram Enterococci, Lactobacilli, Diphtheroids

Primary syphilis

Highly infectious, hard, painless ulcer (chancre) with raised borders on genitalia or mouth Regional lymphadenopathy You can remain asymptomatic for 2-24 weeks 50% cases can spontaneously resolve

63-year-old man presents with anemia and loss of appetite. He denied rectal bleeding. Laboratory studies showed low hemoglobin level, which had been progressively lowering in the past several months. Results were also remarkable for leukocytosis. Colonoscopy revealed no evident source of bleeding. However, a capsule endoscopy demonstrated multiple worm-like objects in the midjejunum, all with a similar curvature and large "heads". Upon further questioning, the patient reported that he frequently walked outside on his farm without shoes.

Hookworm

EF2

Host protein that mediates translocation of the ribosome that is translating an mRNA molecule If this is ribosylated, it halts protein synthesis and will kill the host cell

Intermediate host

Host where maturational stages occur

Definitive host

Host which contains the sexually mature stages

Paratenic host

Host which paints the parasite thru time and space

infectivity

How severe the disease is

Candida spp.

Human commensal, colonize GI tract GI translocation, indwelling device Most common opportunistic fungal pathogen Pleomorphic (yeast, pseudohyphae, hyphae)

How is Chlamydophilia pneumoniae transmitted?

Human respiratory secretions in the form of aerosol droplets

Hyaline vs dematiaceous hyphae

Hyaline is light colored Dematiaceious is dark

Host hygiene and behavior effect on infection susceptibility

Hygiene plays an important role in preventing disease despite exposure. For instance, among a population of people exposed to influenza virus, those who frequently wash their hands or use hand sanitizers are less likely to contract the flu.

Infection by R. typhi diagnosis

IFA/MIF

____ should be used for more serous infections

IV Note: bactericidal is better than bacteriostatic

Important effects of combining two or more different antibiotics: Antagonism

If one antibiotic works kinda well and the other works really well, you can have intermediate killing (the killing effect of the better drug is reduced, but the poorer drug is improved)

septate vs aseptate hyphae

If they have septate, it is the same material as the cell wall but it separates the segments. This is to protect the fungus and prevent the spread of bad things through the whole thing This can be used in the identification Note: this is a special characteristic of hyphae

How is bacterial DNA usually found?

In the cytosol as a single, supercoiled, circular chromosome

Cephalosporins

In contrast to penicillin: -Broader spectrum -More resistant to ß-lactamases Disadvantages: Less potent More expensive Note: these make up 40% of the antibiotics prescribed

Treatment for fever

In normal people, begin with oral acetaminophen. Oral ibuprofen is an alternative to acetaminophen, particularly if anti-inflammatory effect is desired in addition to antipyresis Note: these shouldn't be combined or alternated Note: if the temp remains elevated and the childs discomfort is not improved 3-4 hrs after administration, it is reasonable to switch the medications

Parasites

In the broadest sense, include any organism that colonizes and harms its host. In medical usage, the word "parasite" is reserved for disease-causing protozoa (single-celled eukaryotic organisms) and worms

Plasmid

Independent, self-replicating, circular units of dsDNA, some of which are relatively large (60-120 kb) while others are quire small (1.5-15 kb) Numbers per bacterial cell (copy number) varies for different plasmids ranging from 1-1000 copies/cell. Some are able to replicate in many different bacterial species, others have a more restricted host range

MOA of ionizing radiation (including UV)

Induces lethal DNA damage

Toxocariasis canis lifecycle

Infected animal such as dog or cat is the definitive host. Where the eggs are passed in the feces (note: can be vertical transmission as well) Or from eating infected animals They embryonate in the environment and the L3 larvae can infect other animals, or us The L3 larvae will then migrate to different tissue Note: the Adults are not in our body! therefore we are the intermediate hosts

nosocomial infection

Infection acquired during a hospital stay (hospital-acquired infection) MRSA (methicillin-resistant Staphylococcus aureus)

community acquired infection

Infection acquired in the community, not in a hospital Some MRSA strains are community acquired

disseminated infection

Infection caused by organisms traveling from a focal infection; when affecting several organ systems, it is called a "systemic" infection Tularemia (Francisella tularensis)

mixed infection

Infection caused by two or more pathogens Appendicitis (Bacteroides fragilis and Escherichia coli)

Spaulding Scheme

Infection control strategies used to prepare items/instruments that come in contact with patients are categorized according to the degree of risk and intended use Critical- objects that enter normally sterile tissue or the vascular system should be sterile Semi-critical- objects that touch mucous membranes or skin that is not intact require a disinfection process (high/intermediate level) that kills all but bacterial spores Non-critical- objects that touch only intact skin requires intermediate/low level disinfections

Subclinical infection

Infection has not yet caused signs or symptoms

primary infection

Infection in a previously healthy individual Syphilis (Treponema pallidum)

chronic infection

Infection in which symptoms develop gradually, over weeks or months, and are slow to resolve (heal), taking 3 months or more Tuberculosis (Mycobacterium tuberculosis)

acute infection

Infection in which symptoms develop rapidly; its course can be rapid or protracted Strep throat (Streptococcus pyogenes)

subacute disease

Infection in which symptoms take longer to develop than in an acute (rapid) infection but arise more quickly than for a chronic infection Subacute bacterial endocarditis (Enterococcus faecalis)

Encephalitis

Infection of brain tissue (parenchyma)

A 32-year-old man presented to the emergency department with an 11-month history of fevers, night sweats, paroxysmal coughing, fatigue, and weight loss. He had been treated with a variety of antibiotics for bronchitis during this period but they were not effective. His past medical history was significant for congenital heart disease and he had had a shunt placed as an infant. Farming is his occupation and he participated in birthing his calves. His cardiac exam upon admission revealed a murmur. All standard bacterial and fungal blood cultures were negative. However, serology for Coxiella phase I and phase II antibodies were markedly elevated. Treatment with doxycycline and rifampin was initiated, and the patient rapidly improved. Prolonged treatment was recommended; the patient was non-compliant and rapidly became symptomatic every time he discontinued one or both antibiotics

Infection with Coxiella burnetii

zoonotic diseases

Infections that normally afflict animals but can be transmitted to humans Note: humans typically contract a zoonotic disease after accidentally encountering the animal reservoir.

Arthroconidia

Infective particles of the vegetative hyphae Barrel shaped, thick walled (can withstand harsh conditions) Segementation of hyphae

Chlamydoconidia

Infective particles of the vegetative hyphae Thick-walled Terminal or intercalary

Bastoconidia

Infective particles of the vegetative hyphae Yeasts Bud growth and separation

Why does P. falciparum cause more severe disease?

Infects more RBCs

Lymphadenitis

Inflammation of a lymph node

Infrared thermometry

Infrared TM thermometers measure the amount of heat produced by the tympanic membrane. Temperature readings are close to core temperature, although the infrared TM reflective devices commonly used in homes, hospitals, and offices are considerably less accurate than TM thermistors used in research and by anesthesiologists.

Bacterial portals of entry

Ingestion Inhalation Trauma Skin perforation Arthropod borne (mosquito, etc) Sexual transmission

Ascaris lumbricoides life cycle

Ingestion of eggs from contaminated soil Larvae hatch in duodenum(L1-L2) L2 invade intestinal mucous and travels via systemic circulation to the lungs When in the lungs, they will be come L3 which will migrate across the avelolar wall to the larynx and into the small intestine When you cough, the L3 come up and are then swallowed and will nvade intestinal mucous and travels via systemic circulation to the lungs Other L3 then moults again to form L4 then the adult worm The adult worm lives in the lumen of the small intestine where the female lays eggs which are placed in the stool

Fungi route of infection via infective propagules

Inhalational Traumatic inoculation (splinter, glass, etc. ) Endogenous (part of natural flora)

Rifamycins

Inhibit RNA synthesis by interacting with DNA-dependent, RNA polymerase Therefore it prevents transcription Note: nucleic acid synthesis as an antimicrobial target

Imidazoles and triazoles

Inhibit fungal enzymes to inhibit ergosterol synthesis. Causes Toxic intermediate backup and increased membrane permeability Ex. ketoconazole, itraconazole, fluconazole, voriconazole Note: these are the largest class Note: these can be given orally but are only fungistatic

Bacitracin

Inhibits Bactoprenol cycling therefore inhibiting cell wall synthesis This makes bacteria susceptible to lysis by osmotic stress Note: these are often topical

Vancomycin

Inhibits transpeptidation by binding the D-Ala-D-Ala which prevents it from being used in cross linking reactions It also inhibits the transglycosylation step (I.e. generation of the ß-1,4 sugar linkages) but the underlying mechanisms are less understood The net result is disruption of the cell wall cross linking and synthesis, making bacteria susceptible to lysis by osmotic stress

Ibuprofen

Initial antipyretic gent for children >6mo when antipyretic and anti-inflammatory activity are desired 10mg/kg dose every 6 hours Not for infants younger than 3 mo SE include gastritis and GI bleeding Response should be seen in 60 mins and peaks within 3-4 hr

focal infection

Initial site of infection from which organisms can travel via the bloodstream to another area of the body Boils (Staphylococcus aureus)

Gram positive cross linking: Transpeptidation

Instead of a covalent bond being formed directly between the L-Lys and D-Ala, they have another pentapeptide called a pentaglycine bridge which forms the covalent linkage Therefore, gram positive have a more extensive cross-linking peptidoglycan The D-Ala - D-Ala bond is broken to supply energy for crosslinking and the covalent bond is formed between polymer

Echinocandins

Interfere with synthesis of 1,3-ß glucan synthase Disrupt cell wall integrity Must be given IV Effective against invasive Aspergillosis and systemic Candidiasis Ex. caspofungin, micafungin, anidulafungin

Tetracycline mechanisms of resistance

Interference with transport (ex. drug efflux pumps)

Ketoconzaole

Interferes with synthesis of ergosterol by blocking cytochrome p450 (fungal are more sensitive than mammalian) Fungiostatic Can be used orally SE: related to inhibition of mammalian cytochrome p450 including synthesis of testosterone and estradiol May have important drug-drug interactions

What are the sterile sites in the human body?

Internal organs, blood, CSF These are all sequestered, sterile Note: they might have transient introduction of bacteria into these sites, but we have soluble effectors to clear it out quickly

What locations do adult human flukes parasitize?

Intestines: Fasciolopsis buski Tissues: Paragoniumus westermani Blood: Schistosoma mansoni

C. trachomatis STI

Most frequently reported bacterial STI in US (referred to as a non-gonococcal urethritis- NGU) 1.5 million reported cases ,but prob under reported because many are non-symptomatic Caused by D-K serotypes

Aminoglycosides

Irreversibly binds to the 30S ribosomal subunit causing protein synthesis shutoff and depletion of the 30S ribosome pool. They also can cause misreading of the code leading to defective proteins They are broad spectrum but doesn't affect anaerobes because their import is dependent on oxidation state, so it is harder for them to get in in the absence of oxygen They are synergistic to penicillins Bactericidal

why are there so few invasive fungal infections?

Most fungi are not thermotolerant and cant live in 37C Few have true virulence factors Most people are more "immune normal"

How does tetanus toxin prevent exocytosis of GABA

It is a protease that cleaves synaptobrevin or SNARE proteins that bind the exocytotic vesicles to the membrane

What is the only cell type encode Type III protein secretion apparatus

It must pass through bacterial inner membrane, bacterial outer membrane, and host membrane Therefore only Gram negative cells produce it

Does the response of the fever to an antipyretic agent help to distinguish bacterial from viral infection?

NO

Major clinical findings of Ascariasis

Leukocytosis w/ eosinophilia -Peak during lung phase, decreases as worms mature Hepato- and/or splenomegaly Elevated IgG, IgE and IgA (Serology) Pediatric Findings -Significant cause of malnourishment (impaired intellectual development & motor skills) -Bowel perforation leading to peritonitis -Usually see RTN after treatment

Is DNA ever directly translated to protein?

NO

What are the 3 major direct prep methods for fungal diagnosis

KOH prep (usually with Calcofluor White) (this is rapid and the KOH dissolves away mammalian tissues and not fungi because of cell wall chitin) India ink (not taken up in the cryptococcus) Histopathology & cytology stains: -Gram stain -GMS (best stain for all fungi, fungi stain black) -PAS -H&E -Mucicarmine (stains polysaccharide capsules red)

Is there a fitness cost to expressing virulence genes?

Keeping these things off may be advantageous but turning them on might help in the times of need

Important effects of combining two or more different antibiotics: Synergism

Killing is much more efficient than either antibiotic alone

Bactericidal

Kills, important for serious infection or when natural ability is impaired (diabetes, immune disorders)

Pentapeptide found in Gram negative

L-Ala - D-Glu - DAP - D-Ala - D-Ala Note: DAP is diaminopimelic acid

L. monocytogenes causing meningitis

L. monocytogenes causes ~5-10% of all cases of community-acquired bacterial meningitis in adults in the United States. This diagnosis should be considered in all older or chronically ill adults with "aseptic" meningitis The CSF profile in listerial meningitis most often shows white blood cell (WBC) counts in the range of 100-5000/µL (rarely higher); 75% of patients have WBC counts below 1000/µL, Low glucose levels and positive results on Gram's staining are found ~30-40% of the time.

Common therapy for Leptospira interrogans

Leptospirosis: penicillin, ceftriaxone or doxycycline are used. Ceftriaxone is first choice for meningitis

innate resistance against P. vivax

Lack of duffy blood type determinants on RBCs These serve as receptor sites for P. vivax merozoites

sporotrichosis

Landscaper presents with ulcerated lesions Direct prep: KOH/Calcofluor negative Culture: positive after 14 days at 25C Can undergo thermal conversion to form cigar shaped yeast and hyphae forms

Chalmydiaceae Reticulate body

Larger These begin to form once in the cell within the inclusion Metabolically active/ replicating form Non-infectious No outer membrane protein cross linking --> osmotically fragile

Transposons

Larger, more complex elements than insertion sequences, that encode multiple genes They are >2kb in size and contain genes in addition to those required for transposition (often encoding resistance to one or more antibiotics) Virulence genes, such as this encoding heat-stable enterotoxin from E. coli, have been found on transposons

Environment of the Ileum and colon

Less Bile salts pH 5-7 Anaerobic environment Colonized by facultative aerobes and anaerobes (1/1000 ratio) 90% are Baceroidetes and Firmicutes app

Toxocariasis canis (Toxocariasis)

Life cycle/Epi in Paratenic Human Host: Mouth --> Gut --> Blood --> Tissues Disease: CLM, VLM and OLM -OLM: larvae migration in the eye causes inflammation and scarring on the retina, irreversible vision loss -VLM: larvae migration through parts of the body such as the liver, lungs, or central nervous system and cause symptoms such as fever, coughing, enlarged liver or pneumonia. Diagnostic: Blood test, clinical signs of CLM/VLM/OLM, compatible exposure history Transmission: Humans are accidental hosts who become infected by ingesting infective eggs or undercooked meat/viscera of infected paratenic hosts. After ingestion, the eggs hatch and larvae penetrate the intestinal wall and are carried by the circulation to a variety of tissues (liver, heart, lungs, brain, muscle, eyes). Treatment: VLM --> albendazole or mebendazole

Schistosoma mansoni, S. japonicum, S. haematobium, other species (Schistosomiasis)

Life cycle/Epi: Eggs --> Miracidia --> Snail tissue --> Cercariae --> Human Skin --> Blood/liver Disease: -Early acute phase --> schistosomulum; Th1 immunity (TNFα, IFNgamma, IL1, IL2) ~Upon infection: Skin rash / 1-2 months: fever, chills, cough, and muscle aches Chronic phase --> adults; Th2 immunity (IL4, IL5, IL10, IL13, IgE) -Can persist for years: abdominal pain, enlarged liver, blood in the stool or blood in the urine, and problems passing urine. Chronic infection with S. haematobium can lead to bladder carcinoma and pulmonary hypertension. Diagnostic: Microbiological - Stool O & P / Urine O & P Molecular - Serology, PCR Histology Distribution: South America, Africa, Middle East, Asia Transmission: Skin contact with contaminated freshwater in which certain types of snails that carry the parasite are living. Treatment: Praziquantel

Enterobius vermicularis (pin worm)

Life cycle/Epi: Mouth --> Gut Disease: Incubation 1-2 months. Characteristic symptom: perianal itching. Diagnostic: Tape-prep, 2-3 hours after the child sleeps. (note: eggs are not found in stool!) Distribution: Most frequent in children and caregivers. Transmission: Contaminated hands/surfaces --> mouth Treatment: Mebendazole, pyrantel pamoate, or albendazole. ( one dose--> 2 weeks --> second dose) Note: the medication doesnt reliablly kill pinworm eggs. therefore the second dose is to prevent reinfection by adult worms that hatch from any eggs not killed in the first treatment

Ascaris lumbricoides (Ascariasis)

Life cycle/Epi: Mouth --> Gut --> Lung --> Gut Disease: -Pulmonary symptoms (Loeffler's Syndrome) -High burden: Intestinal obstruction Diagnostic: Stool exam --> O&P (Ova & Parasite) Distribution: Soil-transmitted helminth (STH) prevalent in tropical regions but exists worldwide. Disease of poverty. Transmission: Food contaminated with embryonated eggs Treatment: Albendazole, Mebendazole, Ivermectin

Giardia lamblia and Giardia duodenalis (giardiasis)

Life cycle/Epi: Mouth--> Gut -Cysts are infective stage -Trophozoites multiplying in the small bowel. Disease: Symptoms vary from asymptomatic to severe diarrhea and malabsorption. Acute giardiasis develops after an incubation period of 1 to 14 days (average of 7 days) and usually lasts 1 to 3 weeks. Symptoms include diarrhea, abdominal pain, bloating, nausea, and vomiting. Distribution: Worldwide, travelers, backpackers Diagnostic: Stool O & P Transmission: Contaminated food or water, fecal-oral route (hands and fomites). Treatment: metronidazole Note: GI protozoa

Necatur Americanus, Ancylostoma duodenale (Hookworm)

Life cycle/Epi: Skin --> Lung --> Gut Disease/Clinical: Anemia, pulmonary symptoms Diagnostic: Stool exam --> O&P (Ova & Parasite) Distribution: STH prevalent in tropical regions but exists worldwide. Disease of poverty. Transmission: Skin contact with soil contaminated with human feces. Rhabditiform larvae grow in the feces and/or soil, and molt into filariform larvae (infective). Ancylostoma spp can also be transmitted by oral and transmmamary routes. Treatment: Albendazole, mebendazole. Iron supplements to treat anemia. Prevention: No walking barefoot! Avoid skin contact with contaminated soil.

Taneia solium(pork) and Taenia saginata (beef): Taeniasis & Cysticercosis

Life cycle/Epi: Taeniasis: ingestion of raw/undercooked meat --> tapeworm (gut) Cysticercosis: ingestion of eggs --> cysticerci in tissues (brain, muscles) Disease: Taeniasis vs. Cysticercosis Distribution: worldwide Diagnostic: -Taeniasis: stool for O&P -Cysticercosis: MRI or CT scan; antibody detection in the serum and cerebrospinal fluid Transmission: Ingestion of food contaminated with eggs (cysticercosis) or cysticerci. Prevention: -Taeniasis: cook meat to safe temperature -Cysticercosis: proper sanitation, wash hands, wash well raw vegetables and fruit, good food and water safety practices while traveling in developing countries. Treatment: Taeniasis: Praziquantel or niclosamide Cysticercosis: complex, not always needed; may involve albendazole + praziquantel & anti-inflammatory medication. Symptomatic treatment remains the cornerstone of NCC management.

Trichomonas vaginalis (trichomoniasis)

Life cycle/Epi: woman----> (sex)-->man Disease: -Women: frequently symptomatic. Vaginitis with purulent discharge; vulvar and cervical lesions; abdominal pain; dysuria and dyspareunia. Incubation period is 5 to 28 days. -Men: frequently asymptomatic; occasionally, urethritis, epididymitis, and prostatitis can occur. Distribution: worlwide Diagnostic: wet mounts of vaginal and urethral secretions for women, of urethral and prostatic secretions for men. Transmission: Sexually transmitted disease Prevention: condoms do not provide full protection Treatment: metronidazole or tinidazole

Sarcoptes scabiei (scabies mite)

Life cycle: Egg --> Larva --> Nymph--> Adult Disease: Mite burrow into the intact stratum corneum (outermost layer of the epidermis) and serpiginous burrows in webspace of hands and feet, causing itchiness and rashes. Diagnostic: Based upon the appearance and distribution of the rash and the presence of burrows; confirmed by isolating mites, ova or feces in a skin scraping especially on the hands between the fingers. Distribution: Worldwide. Common in children, crowded populations (jails, nursing homes). Transmission: Skin-to-skin (most common) or via fomites (bedding or clothing). Treatment: permethrin cream, washing/drying all clothing/bedding, treat close contacts.

Pediculus humanus (head lice)

Life cycle: Egg --> Nymph --> Adult Disease: Blood-sucking lice cause intense pruritus with associated excoriations, commonly on scalp and neck (head lice) or waistband and axilla (body lice). Diagnostic: finding live a nymph or adult louse on the scalp or hair of a person, and/or nits attached firmly within ¼ inch of the base of hair shafts. Distribution: Head lice most common among preschool- and elementary school-age children and their household members and caretakers. Much less common among African-Americans. Transmission: head-to-head contact with a person who already has head lice. Treatment: pyrethroids, malathion, or ivermectin lotion, and nit combing. Children with head lice can be treated at home without interrupting school attendance.

Penicillin G (benzyl) and Penicillin V (phenoxymethyl)

Limited spectrum ß-lactamase sensitive

L. monocytogenes causing bacteremia

Listeria rarely causes sepsis or meningitis in immunocompetent individuals. Serious disease typically occurs in the very young, the very old, and immune-deficient individuals. L. monocytogenes septicemia presents with fever, chills, and myalgias/arthralgias and cannot be differentiated from septicemia involving other organisms A nonspecific flulike illness with fever is a common presentation in pregnant women

Clinical manifestations of L. monocytogenes

Listerial infections present as several clinical syndromes, of which meningitis and septicemia are most common.

L. monocytogenes epidemiology

Listeriosis is most often sporadic, although outbreaks do occur No epidemiologic or clinical evidence supports human-to-human transmission (other than vertical transmission from mother to fetus) commonly found in processed and unprocessed foods of animal and plant origin, especially soft cheeses, delicatessen meats, hot dogs, milk, and cold salads

What is the challenge for treatment and diagnosis for human mycoses?

Little is known of pathogenic mechanisms Few are primary ("true") pathogens= insidious Slow growing= culture can be difficult Diverse group of pathogens, many emerging

Endemic dimorphic fungi

Live kinda in the mid eastern US Blastomycosis -Blastomyces dermatitidis -Like to live in soil and decay leaf litter Histoplasmosis -Histoplasma capsulatum -Like to live in bat and bird droppings (High nitrogen)

ectoparasites

Live on the outside of the body, rather than in their hosts usually arthropods (invertebrate animals with an exoskeleton, segmented body and paired jointed appendages) Note: if they themselves dont cause disease, they often serve as vectors of disease (Tick, fleas, etc)

How do we determine whether an antibiotic is bactericidal or bacteriostatic?

Look at turbidity or viability

Common therapy for Borrelia recurrentis

Louse-borne relapsing fever: penicillin or doxycycline are commonly used and effective, For sepsis or mennigitis/cns: intravenous penicillin or ceftriaxone are recommended.

Thryombocytopenia

Low platelet count

Erythromycin

Macrolide that is used primarily against Gram positive bacteria Derivates: Azithromycin and Clarithromycin

Triclosan

Main ingredient in antibacterial soaps Failing out of favor for use due to promoting antimicrobial resistance and issues associated with adverse effects on endocrine function

Case: A 34-year-old woman from Sierra Leone was seen at an emergency department in the Netherlands because of periodic spiking fever that lasted for two weeks. Her medical history was unremarkable, except for uterine fibroids and an episode of malaria several years ago. She has not traveled to malaria endemic regions in the past 10 years. Most striking lab findings were an anemia, thrombocytopenia, and slight leukocytopenia.

Malaria

Two component regulation

Many bacterial virulence genes are subject to positive regulation by these two component regulators which are signal transduction molecules and are typically comprised of two separate proteins One acts as a sensor to detect environmental changes while the tore acts as a DNA binding protein capable of activating (or repressing in some cases) transcription

Aspergillus spp.

Most common opportunistic mould (A. fumigatus) Environmental saprobe

Fungi as pathogen

Massive danger for rice cultivation -Fungal infections destroy enough rice to feed about 600 million people per year $200 billion/year in crop losses Not just due to plant destruction (Aflatoxin in stored foods) Fungal outbreaks currently seen in many animal populations: -Bats - northeast Frogs - worldwide Cats, dogs, and dolphins - northwest 4th most common blood isolate in humans

Common therapy for S. aureus (gram positive)

Methicillin-susceptible -1st generation cephalosporin: cefazolin 2 grams iv every 8 hours or Antistaphylococcal penicillin: nafcillin 2 grams iv every 4 hours -If penicillin or cephlosporin allergic: vancomycin 1-2 grams iv every 12 hours. -The addition of the aminoglycoside often recommended: gentamicin 1mg /kg iv every 8 hours for any of the above therapies Methicillin-resistant -Vancomycin 1-2 grams iv every 12 hours or Daptomycin 6 mg/kg iv every 24 hours

What are the benefits of host-microbe interactions?

Microbes possess biochemical pathways to metabolize substrates into a form that is useable by the human host. Discovering unique biochemical pathways designed by microbial "committee" (they talk to each other, so one produces something that is used by another which then produces something we can use) Microbes produce compounds that we are unable to produce for ourselves (e.g., Vitamins B12 and K) Microbes set up a niche that is fiercely competitive, limited for space and nutrients --> protects us from colonization by pathogenic microbes

Upside of microbiota

Microbiota aid host organ development Help train the immune system Capture carbon and energy for host use Synthesize some vitamins Keep pathogens at bay

Diagnosis of Rickettsia prowazekii infection (epidemic typhus)

Microimmunofluorescence (MIF) test can document epidemic typhus

Majority of fungal pathogens can be classified in 2 major ways:

Mode of sexual reproduction Anatomic site of pathology

Mechanisms of Resistance

Modification of the target so that it is insensitive to an inhibitor but still functions. (ex. Rifamycin where the ribosome mutates to preventing binding of the drug, same for PBP) Duplication of the target enzyme Prevent access to the target Depression of a metabolic activity that normally converts an inert agent into an active agent * Synthesis of enzymes that inactivate an antimicrobial agent or modify the agent to alter entry or binding to a receptor (ex. ß lactamase)

Antibiotics

Molecules (low molecular weight metabolites) produced by microorganisms that kill other microorganisms or inhibit their growth Some common organisms include: Streptomyces, Bacillus, Penicillium, Cephalosporium Note: some are now semi-synthetic or synthetic antimicrobial agent, chemotherapeutic agent

ß lactams

Monobactam Penicillin Cephalosporin Clavulanic Acid (Clavulanate) Carbapenem

2 reproductive styles of human flukes

Monoecious - sexes combined in ea individual fluke Dioecious - live in permanent copula, separate sexes;

Fungal culture

Must be ordered separately from bacteria! Culture allows: -Sensitive recovery of pathogen -Definitive ID by analysis of morphology -Antifungal susceptibility testing Common media: -Non-selective media = Sabouraud-dextrose agar (SDA) -Selective media=SDA-Cycloheximide/Chloramphenicol (SDA-CC) and Inhibitory Mold Agar (IMA) - chloramphenicol -Enriched agar = Brain-Heart Infusion (SABHI) -Blood Culture - automated and manual (media above)

Fungal cell wall: chitin

N-acetylglucosamine chain with (1,4) linkages Major structural component of the wall Biosynthesis is regulated by 3-8 chitin synthase (there is redundancy so cant really target with with antifungals)

Can you grow syphilis in the lab?

NO

Do bacteria have nucleus?

NO

Do killed vaccines for L. monocytogenes provide protective immunity?

NO

Does Orientia tsutsugamushi have PG or LPS?

NO

Does induced or congenital malaria have an exoerthrocytic cycle in the liver?

NO

Do bacteria have introns?

NO! they have co-linear transcripts

Are many pathogens restricted to one system?

NO, bacteria may have tissue preferences but few are restricted to one system Most can disseminate and affect multiple organ systems

For chamydial STI, does previous infection confer protection abasing re-infection?

NO, it confers very little protection

Do Rickettsia prowazekii have actin tails?

NO, they grow to high humber and the cell bursts They replicate in endothelial cells and are spread after lysis of the cell resulting in loss of vascular integrity and rash

Fusidic Acid

Narrow spectrum used mainly for Staphyloccous, but it rarely used Doesnt bind ribosome, it binds the elongation factor G (EF-G)

1st generation cephalosporins

Narrow spectrum (Gram positive cocci)

Transcriptional repressors

Negative regulation and inhibit transcription repressor binds to promoter and prevents RNAP from binding

C. trachomatis STI is often co-associated with ___

Neisseria gonorrhoeae Note: ß lactams are affective against Neisseria but NOT chlamydia they will require a different round of antibiotics

Properties of nematodes

Nematodes are nonsegmented roundworms Most are host-specific 1 of most prevalent communicable diseases of humans (Major cause of childhood malnutrition, growth retardation and impaired cognitive & intellectual development) Larvae & adults are covered by a flexible, durable outer cuticle that is resistant to chemicals Digestive and excretory systems are perforate Genders are separate (ex. Strongyloides stercoralis) -Females are reproductive factories -Most females release shelled eggs, some release live larvae Nematodes utilize a variety of transmission modes

Case History 2: Cindy, a 3-week-old baby was brought to the emergency department because of uncontrollable crying especially when someone tried to turn her head (likely a headache with neck stiffness). She also vomited several times after admission. Other members of Cindy's family were well. Cerebral spinal fluid (CSF) was collected from a spinal tap and sent to the diagnostic laboratory. The CSF appeared cloudy (it should be clear) and contained 871 white blood cells per microliliter (normal is 0-10/µl); the glucose level was 1 mg/dl (normal is 50-80 mg/dl); and the total protein level was 417 mg/dl (normal is under 45 mg/dl). Gram stain of a CSF smear revealed Gram-negative rods. The sample was struck onto chocolate, blood and Hektoen agars for microbial identification.

Neonatal Menigitis caused by Escherchia coli

What is the result of a blood agar culturing Enterococcus faecalis

Non (gamma) hemolysis

Chocolate agar

Non-selective, modified blood agar in which RBCs are partially lysed by heat This medium support the growth of most bacteria, including some that dont grown on blood agar such as Haemophilus and Neisseria strains Haemophilus requires Factor X (hemin) and V (NAD) present in RBCs but they normally lack the ability to lyse RBCs and acquire it Used only to process specimens from microbiota-free sites (blood, CSF)

Do pathogens always leave the same way they came in?

Not always. Obvious examples are diarrhea- causing bacteria and viruses, which enter by ingestion but leave by defeca- tion, where they can again be ingested when food, water, or hands become contaminated (this is the oral-fecal route of transmission

New Delhi Metallo-beta-lactamase-1 (NDM-1)

Not closely related to other metallo-beta lactamases or carbpenemases. Renders ALL the beta lacteal drugs ineffective with the exception of aztreonam Carried on plasmids Produced by antibiotic resistant Gram negative Enterobacteriaceae

Acetaminophen

Not for infants younger than 3 mo 10-15 mg/kg every 4-6 hr Free of SE mostly Response should be seen in 60 mins and peaks within 3-4 hr

Bartonella

Not obligate intracellular Can grow on agar medium with serum and hemoglobin Small Gram negative rod Include: -B. bacilliformis -B. quintana -B. henselae

Serotypes of E. Coli

O Ag (LPS), H Ag (flagella), K Ag(capsule)

Are rickettsia facultative or obligate intracellular pathogens?

Obligate They enter host cell by induced phagocytosis, escape the endoscope, and reside within the cytosol

Coxiella burnetii

Obligate Intracellular bacterium (but can be cultured) Gram negative like rods Grow in acidified vacuole (REQUIRED phagolysosomal fusion) Very stable in the environment Closely related to legionella Causative agent of Q fever

Bacteriophage

Obligate intracellular parasites that consists of a protein coat surrounding a central nucleic acid core

R. rickettsii

Obligate intracellular pathogen Causes Rocky mountain spotted fever Enter via endocytosis and escape to the cytosol which provides immune avoidance Exits via movement within and between cells by actin tails

Ehrlichia and Anaplasma

Obligate intracellular residing within hematopoietic cells Survive in vacuoles (prevent phagolysosomal fusion) Infects monocytes and granulocytes (NOT erythrocytes) Form large membrane- enclosed masses- Morulae

Infection

Occurs when a pathogen or parasite enters or begins to grow on a host.

epidemic disease

Occurs when many cases develop in a community over a short time. An organism need not be endemic to an area to cause an epidemic

Rickettsialpox symptoms

Papule forms at bite site (1 week) followed by Eschar (diagnostic) Systemic symptoms (high fever, severe headache, chills, sweats, myalgia, photophobia) develop after 9-14 days Generalized papulovesicular rash (pox-like)

Many virulence genes are NOT expressed until a biofilm is formed, why?

Often this will protect them from the immune system and allow them to grow to a number sufficient enough to stick around and promote disease

How many chromosomes do bacteria usually have?

One

Is DNA created from RNA?

Only in some viruses

Optochin test

Optochin is a chemical used in paper disks (TaxoP) to identify Streptococcus pneumoniae, which is optochin-sensitive, from other α-hemolytic streptococci such as Streptococcus mutans (Normal oral flora) which are resistant. Taxo P Discs are 6 mm discs made from high quality absorbent paper impregnated with approximately 5.0 g of ethylhydrocupreine hydrochloride (optochin). A blood agar plate is heavily streaked with an alpha-hemolytic Gram positive streptococcus isolated from a clinical specimen, and a TaxoP disk is placed over the streak. During overnight incubation the chemical diffuses into the agar and prevents growth of susceptible species. A zone of growth inhibition around a Taxo P disc is seen if the species is Streptococcus pneumoniae.

Oral thermometry

Oral thermometry generally is preferred in children who are old enough to cooperate. Oral temperature is typically 0.6°C (1.0°F) lower than rectal temperature because of mouth breathing, which is particularly important in patients with tachypnea. Oral temperatures also may be affected by recent ingestion of hot or cold liquids

Strict pathogens

Organisms ALWAYS associated with human disease Note: these are not part of the normal flora

Opportunistic pathogens

Organisms that cause disease only under the 'right circumstances' Note: these are often caused by normal flora

Other epidemiological factors of HAIs include

Organisms with a propensity for transmission within healthcare facilities (e.g. C. difficile, norovirus, respiratory syncytial virus, influenza, group A streptococcus) Organisms that are resistant to first line therapies (e.g. MSRA, VRAS, VRE, ESBL) Organisms that are difficult to treat because of innate or acquired resistance to multiple classes of antimicrobial agents (e.g. Acinetobacter spp. Burkholderia cepacia, Stenotrophomonas maltophilia, quinolone resistant strains of P. aeruginosa) Organisms associated with serious clinical disease and increased morbidity/mortality (e.g. MRSA and MSSA, group A streptococcus)

Superficial and cutaneous mycoses

Outermost layer, epidermis, hair, nails Dermatophyes (ringworm, athletes foot, onychomycoses) Illicit little to no host response Ex. Pityriasis versicolor (Malassezia furfur)

autolysins

PBP enzymes that degrade peptidoglycan at site where new units are added

Malaria pathogenesis

Parasitized RBCs bind vascular endothelium (cytoadherence) Disrupted blood flow Tissue hypoxia and lactic acidosis

Chalmydiaceae

Peptidoglycan is present but is Gram negative like Transports host ATP (energy parasite, pathogen takes up host ATP and spits out ADP to be recharged by the host via obligate antiport systems) They live within a modified phagosome --> Do so by inhibiting phagolysosomal fusion Distinct Life cycle

Chemical sterilants

Peracetic acid -Used on medical/surgical instruments such as endoscopes -Excellent activity with low toxicity Glutaraldehyde -Widely used, especially on respiratory therapy equipment -Non-corrosive, safe for items that are heat/moisture sensitive Ortho-phthalaldehyde (OPA) -Similar to glutaraldehyde

rash pattern in rocky mountain spotted fever

Periphery to body

What is a membrane used for?

Permeability barrier- prevents leakage and functions as a gateway for transport of nutrients into and out of the cell Protein anchor- site of many proteins involved in transport, bioenergetics, and chemotaxis Energy conservation- site of generation and use of the proton motive force

What is the primary phospholipid in bacteria?

Phosphotidylethanolamine Note: eukaryotic's is phosphotidylcholine

How do bacteria attach/adhere/colonize on our body. e.g. How do bacteria in the bladder or colon prevent being swept away?

Pilli Non Pili adhesins (surface protein or carbs) Biofilms Pedestal

A 5 year-old has been constantly scratching the perianal area. The mother noticed restlessness during sleep and fussiness in the past several days. While talking to other parents in the daycare, she found other children with similar behavior.

Pinworm infection

Exotoxins actions:

Plasma membrane disruption: Exemplified by the alpha (a) toxin of Staphylococcus aureus, form pores in host cell membranes and cause leakage of cell constituents. Protein synthesis disruption: Exemplified by diphtheria and shiga toxins, targets eukaryotic ribosomes and destroys protein synthesis. Signal transduction disruption: Subverts host cell secondary messenger pathways. Cholera toxin and E. coli ST (stable toxin), for instance, cause runaway synthesis of cAMP (described later) and cGMP, respectively, in target cells. Elevated cAMP or cGMP levels, in turn, trigger critical changes in ion transport and fluid movement. Cell-Cell adherence: These exotoxins are proteases that cleave proteins binding host cells to one another. Exfoliative toxin of Staphylococcus aureus, breaks the connection between dermis and epidermis (desmoglein 1 is cleaved by the toxin), giving victims a gruesome scalded skin appearance. Exocytosis: Protease toxins that alter the movement of nerve cell cytoplasmic vesicles to membranes where they release neurotransmitters. One example is tetanus toxin, which cleaves host proteins required for exocytosis of the inhibitory neurotransmitter gamma amino butyric acid. Superantigens: Activate the immune system without being processed by antigen-presenting cells. The pyrogenic (fever-producing) toxins of Staphylococcus aureus (such as toxic shock syndrome toxin) and Streptococcus pyogenes are examples of superantigen toxins.

_____ carriers genes for resistance to several different antibiotics

Plasmid, transposon, integron

Malaria is caused by _____

Plasmodium falciparum -It can be rapidly fatal and must be immediately ruled out in all febrile persons who have recently visited an area when malaria is endemic (sub-saharan africa) -Most begin having symptoms within 1 month of return Plasmodium vivax -Acquired in Asia or Latin America -Less likely to begin having symptoms within 1 month of return Note: patterns of fever are rarely diagnostic, but infections with P. vivax, P. ovale, and P. malaria infections occur at regular intervals of 48 to 72 hrs

Recrudescence of falciparum and malariae

Plasmodium falciparum and P. malariae do not develop latent hypnozoites in the liver and thus lack the capacity to relapse Recrudescence of falciparum and malariae is different from relapse (vivax and ovale) because there are no liver hypnozoites in the former that become latent. Therefore, effective treatment with exoerythrocytic drugs will not leave latent parasites. Only need to destroy parasites in the peripheral circulation

Antifungal toxicity

Polyenes -Renal toxicity (non-lipid formulations) -Liver toxicity (high dose lipid formulations) Triazoles -Liver and renal toxicity with some chemotherapeutics Echinocandins -Less toxic (very fungal-specific), limited clinical efficacy -Expensive!

Are Neisseria meningitidis and Neisseria gonorrhoeae oxidase positive or negative?

Positive

Is staphylococcus aureus catalase positive or negative?

Positive

Benefits of fever

Potential benefits of fever include retardation of the growth and reproduction of some bacteria and viruses (perhaps related to decreased serum iron) and enhanced immunologic function at moderately elevated temperatures (although some of the benefits are reversed at temperatures approaching 40°C [104°F]).

Factors promoting susceptibility of patients to HAIs include:

Preexisting conditions that weaken the immune system Use of diagnostic procedures, therapeutic procedures (e.g. IV antibiotics), invasive techniques, and medical devices (e.g. in-dwelling catheters and mechanical ventilation) that provide microbes with portals of entry (infection risk increase that longer devices remain in-dwelling) Lack of complacent with basic infection prevention measures (e.g. hand washing or use of alcohol based hand cleansers by hospital staff)

septicemia

Presence and replication of bacteria in the blood (blood infection) Bubonic plague (Yersinia pestis)

bacteremia

Presence of bacteria in blood. Usually transient, little, or no replication May occur during dental procedures (Streptococcus mutans)

Chlorhexidine

Present in skin cleansers and oral rinses; not as effective as alcohols at killing

Indications for use of antimicrobial combinations

Prevent the emergence of resistant organisms (odds to having two or more different mutations that provide resistance to many different antibiotics is lower) Polymicrobial infections Initial therapy Decreased toxicity Synergism

Chlamydophila psittaci

Primarily zoonotic coming from births (ornithosis) and parrots (psittacosis) Can be transmitted to humans Leads to respiratory tract infection which can spread to the liver/spleen and then back to the lungs via the blood Fewer than 50 cases in U.S. but very dangerous and highly infectious with 5% mortality Note: people working with animals are most at risk

Botulinum toxin

Produced by Clostridium botulinum Works at the neuromuscular junction by inhibiting release of ACH (It is a protease that cleaves synaptobrevin or SNARE proteins that bind the exocytotic vesicles to the membrane) This leads to flaccid paralysis Note: this can come from improper home canning, honey, etc

Diphtheriae Toxin

Produced by Corynebacterium diphtheria and results in a grey/white exudate in the back of the throat This toxin comes from bacteriophage beta (a lysogenic phage) which carries the toxin gene Has 'A' subunit which is an ADP-ribosylating enzyme targeting host protein . This adds NAD+ to the target protein (EF2) inactivating the ribosome Has 'B' subunit which binds to a host receptor to facilitate toxin uptake This halts host cell protein synthesis and causes its death

Cholera toxin

Produced by Vibrio cholera which is an enteric pathogen (Gram negative, curved rod) and disrupts host cell signal transduction pathways Infection produces watery diarrhea --> rice water stools CTX is an ADP-ribosyltransferase (encoded by a lysogenic phage) It adds an ADP ribose to a G-factor that controls adenylate cyclase. This results in high cAMP levels which stimulate ion export out of the cell and water follows, causing diarrhea

Examples of factors contributing to a microbes ability to cause disease

Production of extracellular polysaccharides (e.g., capsules & biofilms) Growth and consequent destruction of host tissues Cell-to-cell spread via actin motility (dont need to enter extracellular space) Ability to disseminate from the initial site of infection (bacteremia, SIRS, sepsis, septic shock) Induction of host inflammatory responses that causes cell and tissue damage (mediated by PAMPs and DAMPs overstimulating TLRs resulting in a cytokine storm) Secretion of toxins and effector proteins that alter normal host cell physiology (sometimes ingestion of a toxin is enough to make you sick) Secretion of factors to scavenge nutrients (e.g., siderophores scavenge iron from host proteins such as transferrin) Secretion of 'stealth' factors that hide pathogens from the immune system (ex. Hep B)

Where is bacterial transcription initiated?

Promoter regions which are recognized by sigma factors includes: -35 box (TTGACA) -10 box (TATAAT) Note: this helps bacteria coordinate gene expression

Use of antifungal agents

Prophylactic -Prevent infection in high-risk patients (ex. burn patients) Preemptive -Use in patient with positive diagnostic test, but no sign of disease Empiric -Sign and symptoms but no definitive ID Definitive therapy -Proven fungal infection

Lincomycin and the derivative Clindamycin

Protein inhibitor with increased spectrum and potency Interferes with peptide bond formation Effective against anaerobes (e.g. Bacteriodes fragilis) However, it may induce overgrowth of Clostridioides difficile leading to pseudomembranous colitis (inflammatory problem in gut)

LacI Repressor

Protein which negatively regulates the lac operon Encoded by lacI gene, which is located immediately upstream of the lactose operon and transcribed by a separate promoter

To stay with us, members of our normal microbiota have _______ that allow them to attach to and colonize epithelial cells lining mucous membranes (intestines, urinary tract, mouth, nose)

Proteins on their surface called adhesins

Major groups of endoparasites

Protozoans: single cell organisms Flatworms & Roundworms: multicellular worms

A 42-year-old female presents to the Emergency Department (ED) complaining of passing profuse green-colored loose stools she describes as foul smelling and 'greasy and bloody' in appearance. She also complains of frequent cramping and nausea. Patient's temperature is 104 oF / 40 oC. She reports being treated over the last 2-3 weeks with several different 'kinds' of antibiotics as part of a recent surgery but doesn't recall the specific antibiotics. The patient is admitted and a colonoscopy ordered.

Pseudomembranous enterocolitis caused by Clostridioides difficile

_____ makes a similar toxin to the diphtheria toxin

Pseudomonas aeruginosa

Pathogenesis of Ascarasis

Pulmonary Phase -Eosinophil-rich pneumonitis (Cough, bloody sputum) -Parasite metabolites are Th2 stimulants ~IL-4, IL-5, IL-13 are signature cytokines ~IgE, Eosinophils, Airway Hyperresponsiveness Intestinal Phase -Symptoms proportional to adult worm burden ~Most patients have a few worms, a few patients have the most worms (truism for many helminthic infections) ~Most patients tolerate their infections well Small children often have intestinal or biliary obstruction

Acute infection with Coxiella burnetii

Q fever Severe headache Fever Chills Myalgia Symptoms of atypical pneumonia

What are the 2 important factors of success in management of fungal infections

Rapid diagnosis Immune status of host (must be good)

Pathogen attachment

Recall that specific proteins (adhesins) on the surfaces of microbes help them adhere to host cells, like a thumbtack to a corkboard. Microbial adhesin proteins bind to structures called receptors on host cell surfaces. Because different host cells in different tissues have different receptors, a pathogen will have a preference (predilection) to infect tissues whose cells are lined with the right receptors. Pathogens that fail to attach to the host can be expelled.

Sigma 38

Recognizes promoter sequence and coordinates general stress genes such as in the stationary phase Note: this helps bacteria coordinate gene expression

Sigma 70

Recognizes promoter sequence and coordinates housekeeping genes Note: this helps bacteria coordinate gene expression

Sigma 54

Recognizes promoter sequence and coordinates nitrogen stress genes Note: this helps bacteria coordinate gene expression

Rectal thermometry

Rectal thermometry is generally considered the reference standard for measurement of core body temperature, but there is a lag between changes in core body temperature and temperature in the rectal vault. Rectal thermometry is usually performed in infants and young children if the result has clinical implications. The majority of studies establishing the risk of serious infections in febrile infants and young children have relied on rectal temperatures. Rectal thermometry is contraindicated in patients with neutropenia

Orientia tsutsugamushi Reservoir and vector

Reservoir: Mite (rodent serves as reservoir for mites) Vector: Mite (transovarian reservoir)

R. typhi vector and reservoir

Reservoir: Rodents Vector: Flea- rat and cat (cat flea thought to be important in U.S.)

R plasmids

Resistance genes on conjugative plasmids which confer resistance to antimicrobials May carry genes for resistance to several antimicrobials (ex. R1 confers resistance to 6 antibiotics) Can recombine so that individual plasmids can be responsible for new combinations of multiple drug resistance

Properties of stationary phase cells

Resistant to: -Acid pH -Heat shock -Oxidative stress Note: they change their genes and therefore 'differentiation' is used as a mechanism for coping with stress

Upper respiratory tract infection

Rhinitis Sinusitis Pharyngitis (strep throat) Tonsilitis Tracheitis Epiglotittis Laryngitis Note: this is a mucosal infection

Phenotype

The physical characteristics of an organism based on its genotype and interaction with ints environment

Endemic Typhus

Saused by Rickettsia typhi Found in warm, humid areas (gulf states) Similar in incubation and symptoms to other rickettsial diseases

Case History 3: Parents bring their 2 month old baby to the emergency department. The baby has blisters over much of her body and her epidermis was peeling off in patches. The child, in obvious pain, looked like she was bathed in boiling water. The parents said that the symptoms started as a single blister that spread over the next 12 hours.

Scalded skin syndrome. Organism set up an infection at some body site (nose?) and secreted the exfoliation toxin.

Hektoen Agar

Selective for gram negative (contains bile salts and acid fuchsin inhibiting gram positive) Medium contains lactose and sucrose, any organism that can ferment either of those sugars such as E. coli acidifies the medium and absorbs dyes that give colonies a yellow-orange hue Non fermentors colonies appear colorless such as Salmonella and Shigella. These are differentiated by H2S production. Salmonella produces H2S which reacts with Fe to make FeS and a black center

52 year-old Sudanese woman admitted to hospital complaining of left hypochondrium pain. Vitals normal, no stigmata of chronic liver disease and infective endocarditis, no jaundice. On abdominal examination, there was massive splenomegaly. Blood test showed pancytopenia. Patient said her sources of drinking water are from canals and wells, where both are infested with snails. Sanitation is poor, canals used as toilets.

Schistosomiasis

Common therapy for N. meningitidis (gram negative cocci)

Sepsis with predilection for CNS and meningitis -3rd generation cephalosporin, eg.,Ceftriaxone, high doses. This class of antibiotic is used because of its excellent penetration into the CNS for treatment of meningitis (readily crosses the blood brain barrier)

Common therapy for S. typhi (gram negative rod)

Septicemia and typhoid fever -Many cases resolve without antibiotics but may need hospitalization for supportive care -Resistance to penicillins, cephalosporins, tetracyclines is common worldwide. -Quinolone class of antibiotics are usual 1st choice (although resistance to this class is also increasing) -May need very broad spectrum iv antibiotics (carbapenem class of antibiotics)

Septicemia and disseminated infections

Septicemias are one of the most serious and often life-threatening infections. Once in the bloodstream, the pathogens can be disseminated throughout the host Multiorgan involvement and damage is the rule Important to start antibiotic therapy as soon as possible - Treat broadly for empiric coverage of the most likely pathogens (cannot risk missing a common pathogen) - Narrow spectrum once the pathogen has been identified Important to find and remove the source of the sepsis (source control), eg., surgically drain an abscess, whenever possible

Shine-Dalgarno sequence

Sequence in the bacterial mRNA where ribosomes bind and begin translation at a start codon (AUG) which hydrolyzes with a spefici complementary sequence (anti-codon) of the fMet

Chlamydophila psittaci diagnosis

Serology (can be grown in cell culture, although it is rarely done)

Diagnosis of Coxiella burnetii

Serology used for diagnosis and IFA and PCR is available

How do you diagnose pathogens that do not grow in the lab?

Serology: -Look for antibodies in the blood that specifically bind the organism. -These antibodies only arise if the patient was infected AT SOME TIME. -Typically we look for a specific high titer of antibody, or a greater than 4-fold rise between antibodies in acute vs convalescent phases of disease. Polymerase chain reaction - you can find signature DNA markers of microbes currently infecting the patient.

Transmission of syphilis

Sexual (horizontal transmission) Vertical transmission to fetus

Basidomycota

Sexual reproduction Asexual = rare Septate Many are mushroom forming Cryptococcus, Schizophyllum, and Malassezia

Mucormycotina

Sexual reproduction Less than 1000 spp. Asexual reproduction = sporangiophores Aseptate hyphae Fast growing Mucor spp. Rhizopus spp.

Ascomycota

Sexual reproduction More than 30,000 spp. Asexual reproduction = conidiophore Septate hyphae Candida

The patient was a 6-year-old female from North Carolina. She was in the usual state of good health until 10 days prior to admission, when she had a tick removed from her scalp. She developed sore throat, malaise, and a low grade fever 8 days after tick removal. She was seen by her pediatrician when she began developing a pink, macular rash, which started on her palms and lower extremities and spread to cover her entire body. The pediatrician's diagnosis was viral exanthem. One day prior to admission, she developed emesis, diarrhea, myalgias, and increased fever. On the day of admission she was taken to her local hospital emergency room because of mental status changes and was admitted. Ampicillin and chloramphenicol therapy was begun, and she was intubated and transferred to a larger hospital. She died soon after.

She had Rocky mountain spotted fever caused by R. rickettsia

______ toxin causes hemolytic uremic syndrome

Shinga

What are some exotoxins produced by Escherchia coli

Shinga toxin Cholera-like toxin (LT)

Indications for the short-term treatment of fever may include:

Shock Underlying neurologic or cardiopulmonary disease, or other condition with increased metabolic rate (eg, burn, postoperative state) Alteration in fluid and electrolyte balance High fever (ie, ≥40°C [104°F]) Discomfort Major head trauma Postcardiac arrest

prodromal phase

Short and may not even be apparent. It involves vague symptoms, such as headache or a general feeling of malaise (fatigue and mild body discomfort), that serve as a warning of more serious symptoms to come.

malaria treatment

Should get as soon as possible Halofatrine not for use in USA because of adverse heart effects those who take chloroquine were there is a resistance or use less than optimal drug regimens are at increased risk for acquiring malaria Two malaria treatment regimens can be prescribed as a reliable supply treatment: atovaquone- proguanil and artemether-lumefantrine

Spectinomycin

Similar to ahminoglycosides (aminocyclitol) Binds to 30S therefore inhibiting protein synthesis but is bacteriostatic

diagnosis of malaria

Smear microscopy Various rapid diagnostic test kits (RDTs) to detect antigens derived from malaria (cant determine species or quantity)

What are the properties of protozoans

Singled celled, eukaryotic organisms May be intracellular -Leishmania spp. -Plasmodium spp. (Malaria) -Trypanosoma cruzi (Chaga's organism) May be extracellular -Amoebae (Entamoeba histolytica and Naegleria fowleri- brain eating amoebae) -Giardia intestinalis -Trypanosoma brucei -Trichomonas vaginalis Replicate by binary fission with variations to enhance fecundity Can live in GI, tissues or vasculature

Where is Staphylococcus aureus found?

Skin, nares (it is a part of the normal flora)

Rickettsia

Small (0.4 x 1.0 µm) Gram negative rods (have peptidoglycan and an outer membrane) Grow in the cytosol (no vacuole) They are unstable in the environment Energy parasites (ATP/ADP translocase) Biosynthetically deficient (e.g. cant synthesize amino acids) Transport is important (need to be able to move things across their membrane are very important)

Insertion sequences

Small (<2kb) jumping genes composed of a transposase gene (required for transposition) flanked by short inverted repeat sequences (required for locating/inserting into DNA) Serve important functions as portable regions of homology throughout bacterial genomes. They enable chromosomal integration of plasmids into the bacterial chromosome

Bacterial forms of coxiella burnetii

Small cell variant- Environmentally stable form that can last months to years and is the infectious form Large cell variant- replicating form

Chalmydiaceae Elementary body

Small, theses differentiate from the reticulate body within the inclusion Infectious Outer membrane protein highly cross-linked [S-S] to give environmental stability and persist for long periods of time once it's released Metabolically inactive

What is the result of a blood agar culturing staphylococcus pneumoniae

α hemolysis

How do anaerobes establish a proton motive force if they dont possess an ETS?

Some anaerobes don't have complex 4 because they lack an ETS, but they do have a complex 5! It runs in reverse such that H+ are pumped out of the cell into the extracellular environment and build up the proton gradient Note: this requires ATP generated from fermentation to power

Pedestal formation

Some diarrheagenic E. coli inject their own receptor made in their cytoplasm into the host cell cytoplasm, along with other bacterial proteins via Type III protein secretion apparatus (like a molecular syringe and) This allows them to hijack host actin polymerizing mechanisms and form the pedestal Note: they inject a virulence factor into the cell and then express a protein that binds to the virulence factor and allow the microbe to attach tightly to the host. As a consequence, the bacteria will remodel its actin cytoskeleton and get pedestal formation

What are the different options for intracellular pathogens once they are in the cell?

Some thrive in acidic conditions and reside within the phagolysosome such as Coxiella Some prevent the fusion of the phagolysosome such as Salmonella. They can use their Type II secretion to remodel the vacuole make it not "appear" as a endosome and therefore it doesn't fuse Some escape the phagosome and reside in the cytoplasm such as Shigella and Listeria (note: these use proteins that can cause actin remodeling and this polymerization can be used to move around and propel into another cell)

Viability

The process of making serial dilutions, plating each concentration, and looking for growth on a plate This involves only the live specimens

Resistance to multiple antibiotics

Soon after antibiotics became common therapeutic agents (sulfonamides, streptomycin, chloramphenicol, and tetracycline) strains of Shigella were isolated from patients in Japan that were resistant to all four drugs. These strains began to appear frequently and similar resistance was subsequently found in Escherichia coli and in Salmonella species. It was discovered that these resistances could be transferred simultaneously to a number of different organisms and that the transfer required cell-to-cell contact (conjugation).

neurocysticercosis treatment

Specific anthelminthic therapy, surgery, corticosteroids, and treatment of symptoms Praziquantel or albendazole for anthelminthic or a combination of both is indicated for parenchymal lesson s and meningoencephalitis surgical removal is indicated in single parenchymal, intraventricular, spinal, and ocular cysticerci. Supportive measures include ventricular shunts for hydrocephalus, corticosteroids which can help in reducing mass related oedema, and anti-epileptic agents.

Factors to consider when selecting an antibiotic

Spectrum Tissue penetration (bone infections are often hard to treat because the penetration is poor) Antibiotic Resistance Safety profile Cost

Spirochetes phenotype

Spiral shape (unique flagella that allows them to move in a corkscrew fashion)

Does Mucor, Rhizopus aerial hyphae produce conidia or spores?

Spore

Case History 2: 25 y old pastry chef cut her left forearm with a knife during work. Over the week her arm became red, swollen and warm at site. 4 days later, she developed fever with shaking chills. Presented to emergency room with severe low back pain. Temp of 39.4C (102F), right forearm swollen with area of central softness indicating abscess. Also tenderness to pressure over lower spine. Lab reported high white cell count (left shift), Gram stain of pus showed purple clusters of cocci X rays of lower spine showed erosion of 3d lumbar vertebra suggesting osteomyelitis. Antibiotic resistance tests showed org. was penicillin-resistant but oxacillin-sensitive.

Started as an abscess. Organism disseminated through blood stream to infect vertebrae and her other arm (metastatic lesions).

Bacteriostatic

Stops growth allowing host defenses to catch up and clear it out

Quinupristin/Dalfopristin (Synercid)

Strepogramins Used against Gram positive bacteria A synergistic combination- Dalfopristin prevents peptide chain elongation while quinupristin initiates premature release of peptide

Underlying noninfectious diseases or conditions effect on infection susceptibility

Substance abuse as well as several medical conditions can place an individual at higher risk of infections. For example, alcoholics are very susceptible to infections because, along with decreasing the libido, alcohol use can depress facets of the immune system. Diabetics are at increased risk for many infections because of hyperglycemia-related impairment of immune responses, vascular insufficiency (decreased blood flow), increased skin and mucosal colonization, as well as other factors. Serious infections on the soles of the feet are common in diabetic patients because sensory nerve damage (neuropathy) caused by hyperglycemia (excess glucose in the blood) prevents them from feeling the beginning of an infection. Smoking not only increases the risk of lung cancer but also increases the number of respiratory infections because of smoke's paralyzing effect on the mechanisms designed to sweep bacteria up and out of the lung. Even sleep deprivation can dampen immune responses.

Domagk

Sulphanilamide & Isoniazid

Types of fungal infections

Superficial and cutaneous mycoses Subcutaneous mycoses Systemic mycoses Opportunistic pathogens

Acute infection

Symptoms arise quickly, short course

Chronic infection

Symptoms arise slowly, long course, major immunological component

Toxemias

Symptoms due to toxin rather than bacterial growth (botulism, tetanus, toxic shock syndrome)

L. monocytogenes diagnosis

Symptoms of listerial infection overlap greatly with those of other infectious diseases. Timely diagnosis requires that the illness be considered in groups at risk: pregnant women; elderly persons; neonates; individuals immunocompromised by organ transplants, cancer, or treatment with TNF antagonists or glucocorticoids; and patients with a variety of chronic medical conditions, including alcoholism, diabetes, renal disease, rheumatologic illness, and iron overload. Meningitis in older adults (especially with parenchymal brain involvement or subcortical brain abscess) should trigger consideration of L. monocytogenes infection. The diagnosis is typically made by culture of blood, cerebrospinal fluid (CSF), or amniotic fluid

Latent state

T he organism cannot be found by culture. Herpes virus, for instance, can enter the peripheral nerves and remain dormant for years and then suddenly emerge to cause cold sores Note: there are no symptoms or clinical evidence of the infection

Dilution streaking technique

Take specimen and spread over the agar and streak from the previous quadrant (after the loop has been heated) As we spread them out, we can get single colonies which are assumed to arise from a single bacterium We then can culture this colony and get a pure (clonal) culture of the causative bacteria

Polyene antifungals

Targets fungal cell membranes They affect membrane permeability by interfering with ergosterol biosynthesis Ex. Imidizoles (Miconazole, Ketoconazole, Fulconazol) and Amphotericin B

Polymyxin (colistin)

Targets the cell membrane and is used as a last resort They get into the membrane and have detergent like properties which will solubilize the phospholipid molecules. This weakens the cell membrane and causes lysis

Translation

The process by which mRNA is decoded to produce a protein which is achieved by ribosomes and tRNA molecules

Chlamydophila psittaci treatment

Tetracycline or Macrolides

Treatment for R. typhi infection (endemic typhus)

Tetracyclines

What antibiotics should not be used in pregnant

Tetracyclines Doxycyclines Quinolones Chloramphenical

Susceptible

The MIC for the pathogen can be achieved in the body at recommended doses

Resistance

The MIC for the pathogen can not be achieved in the body at recommended doses

A 35 year old vegetarian Indian woman who had been living in the UK for three years presented in the emergency department with a first episode of seizure after a trip to India. She had undergone total thyroidectomy for toxic nodular goitre in the UK earlier in the year and was taking calcium supplements. She had experienced vague abdominal discomfort two weeks before the seizure. The patient's grandmother, whom the patient visited during her trip to India, had experienced delirium, dizziness, and headaches two months before the patient's visit. These symptoms self resolved and were not investigated. In addition, the patient's husband also experienced vague abdominal discomfort similar to the patient's, two weeks before she presented. The woman had a magnetic resonance imaging (MRI) scan in the emergency department (). What is the diagnosis based on the MRI findings?

The MRI shows a lesion with scolices and perilesional oedema around the right frontal lobe. This is a classic sign of neurocysticercosis. The patient was treated with a combination of anthelmintic therapy with albendazole and praziquantel for two weeks. She also received a week's course of corticosteroids and remains on anti-epileptic treatment with carbamazepine. She remains stable at present with no further seizures.

Colonization

The ability of a microbe to stay affixed to a body surface and replicate

Biofilm Quorum Sensing

The bacteria secrete small signal molecules and the concentration of the molecules is proportional to the number of microbes in the community. They use this to "count" and turn genes for biofilms on or off

Coagulase test

The coagulase test is used to differentiate between different species of Staphylococcus. S. aureus is coagulase positive, S. epidermidis coagulase negative. The test is carried out on a glass slide as a latex agglutination. Latex beads coated with plasmin are mixed with bacteria. If the bacteria produce coagulase, the latex beads agglutinate (clump).

Chaga disease diagnosis and treatment

The cardiac form is the most serious and frequent manifestation of chronic Chagas disease. It develops in 20-30% of individuals and typically leads to abnormalities of the conduction system, bradyarrhythmias and tachyarrhythmias, apical aneurysms, cardiac failure, thromboembolism, and sudden death. Diagnosis: serology and tissue biopsy Treatment: Benznidazole or Nifurtimox / Heart transplant Pregnancy: In pregnant women, consider risk-benefit ratio as with other potentially teratogenic drugs. Limited experience with benznidazole has not shown neonatal abnormalities. Treatment failure is usually seen as a positive PCR result. Consider retreatment. Combination therapies and longer drug courses can be considered.

Selective Toxicity

The central concept of antimicrobial action The growth of the infecting organism is selectively inhibited or the organism is killed without damage to the cells of the host

Defined growth media

The chemical makeup is known because you added it.

How do you tell one E. Coli from another?

The classification is important for epidemiological purposes Different pathogenic E. coli are assailed with different O, H, or K antigen serotypes (e.g. O157:H7) You could use PCR (NAAT tests) to distinguish They also have pathogenicity genes associated with: -plasmids -prophages -pathogenecity islands on chromosomes

Properties of ideal antibiotic

The drug should be low in toxicity to the host's cells while destroying or inhibiting the disease agent; (i.e., it must demonstrate selective toxicity) The host should not become hypersensitive (allergic) to it. The host should not destroy, neutralize, or excrete the drug until after the drug has performed its function. The organism should not readily become resistant to the drug.

CDC campaign to prevent antimicrobial resistance

The first and best way is to vaccinate and prevent the infection to begin with!

Hygine hypothesis

The idea that our lessened exposure to diverse microbes has predisposed us to allergies and autoimmune diseases

Lifecycle of Trypanosoma cruzi

The kissing bug ingest kissing bug epimastigotes which travel to the handout and differentiate into metacyclic tryposmatigoes that are released by deification Trypomastigoes are the infective form which infect humans and travel to the blood stream and affect many different tissues Especially the heart causing cardiomyopathy, colon, esophagus, within the chronic phase The acute phase will see romana sign and chagoma

Minimum inhibitory concentration (MIC)

The lowest concentration that inhibits the growth of the organism

Minimum bactericidal concentration (MBC)

The lowest concentration that kills the population

Empiric therapy signs and symptoms that prompt antifungals

The management of fungal infections is often more difficult than bacteria, therefore treatment is often started before etiologic agent is identified These signs and symptoms include: Profound neutropenia and fever of unknown origin failing to respond to antibacterials

Sites of temperature measurement

The most common sites of temperature measurement in clinical practice are the rectum, mouth, and axilla; in addition, pattens and caregivers may measure temperature at the tympanic membrane or forehead (each of these sites has its own range of normal values)

Lethal dose 50% (LD50)

The number of bacteria or virus particles (virions) required to kill 50% of an experimental group of animal hosts (usually mice or guinea pigs). An organism with a low LD50, in which very few organisms are required to kill 50% of the hosts, is more virulent than one with a high LD50

Genotype

The physical arrangement of nucleotides in the DNA of an organism; often discussed in terms of gene arrangement

Transovarial transmission

The transfer of a pathogen from parent to offspring by infection of the egg cell. Typically seen in insects.

Transformation

The uptake and stable expression of exogenous DNA

Self prescription (get from relatives, etc)

The use of these antibiotics in these uncontrolled and often unnecessary conditions is high in developing countries, ranging from 20 to 40% Promoting compliance also reduces a common source of self-prescription; the use of antibiotic leftovers, often inadequate and expired

L. monocytogenes infection in pregnant women and neonates

The usual presentation is a nonspecific acute or subacute febrile illness with myalgias, arthralgias, backache, and headache. Pregnant women with listeriosis are usually bacteremic. This syndrome should prompt blood cultures, especially in the absence of another reasonable explanation. Involvement of the CNS is rare in the absence of other risk factors. As many as 70-90% of fetuses from infected women can become infected. Prepartum treatment of bacteremic women enhances the chances of delivery of a healthy infant. Granulomatosis infantiseptica is an overwhelming listerial fetal infection with miliary microabscesses and granulomas, most often in the skin, liver, and spleen "Late-onset" neonatal illness typically develops ~10-30 days postpartum

Bacteriostatic protein synthesis inhibitors

Their structure differ considerably and in many cases the structure cannot be associated with the mechanism of action Most bind to the 50S ribosomal subunit Though a few dont! -Tetracycline: 30S -Spectinomycin: 30S -Fusidic acid: Elongation factor -Oxazolidinones: Initiation complex (and 50S?)

Systemic mycoses: endemic dimorphs

There are certain parts of the US where you will find these Must travel through these areas to come in contact with the fungus These are saprophytic fungi which means they grow out in nature and consume decaying material They can cause mild, flu like symptoms but can also cause severe invasive disease

Problem with Hfr strains

These are able to transfer large region of genomic DNA to the recipient DNA transfer never goes to completion, thus the recipient cell does not become Hfr (I.e. the recipient cannot initiate subsequent gene transfer)

Diarrheagenic statins of E. Coli

These are all highly acid resistant! Enterotoxigenic strains (ETEC) Enteroinvasive strains (EIEC) Enterohemorrhagic strains (EHEC) Enteropathogenic strains (EPEC) Enteraggregative strains (EAEC)

Mycelium

These are colonies and are basically a network of filaments

CDC Urgent Threats

These are high-consequence antibiotic-resistant threats because of significant risks identified across several criteria. These threats may not be currently widespread but have the potential to become so and require urgent public health attention to identify infections and to limit transmission. Include: Clostridium difficile Carbapenem-resistant Enterobacteriaceae (CRE) Drug-resistant Neisseria gonorrhoeae

CDC Serious threats

These are significant antibiotic-resistant threats. For varying reasons (e.g., low or declining domestic incidence or reasonable availability of therapeutic agents), they are not considered urgent, but these threats will worsen and may become urgent without ongoing public health monitoring and prevention activities.

Gnotobiotic Housing

These produce a sterile environment for animals to live in. These animals have: -poorly developed immune system -lower cardiac output -thin intestinal walls -more susceptible to infections -colonization with normal flora alters host gene expression

In humans, how does R. rickettsii cause problems

They grow within endothelial cells of various organs This causes damage to the cells, vascular leakage, and rash Note: rash typically beings on extremities, involving palms and soles, then covers obeyed. Rash may not be been in some cases (10%)

What cell types do C. trachomatis (trachoma and STI) like?

They have a limited range of cell types that infect in vivo They like Non-ciliated columnar, cuboidal, and transitional epithelial cells (mucous membranes or urethra, cervix, conjunctivae, etc.) They gain access through micro abrasions

Why are virulence factors essential to the pathogen?

They help establish colonization: Modes of Transmission (how we come in contact) and Portals of Entry (how the get in) "Sticking Around" (Adhesion) "Location, location, location" (Extracellular vs. Facultative Intracellular vs. Obligate Intracellular Pathogens) Surviving Host Defenses (Physical Barriers vs. Innate Immunity) Deployment of specific virulence factors to alter host physiology (toxins)

Penicillins mode of action

They interact with penicillin binding proteins (PBPs) (example of a PBP is transpeptidase) which are used in the synthesis and remodeling of peptidoglycan It prevents crosslinking causing a weakened cell wall and a cell that will eventually pop due to osmotic pressure

Thayer-Martin agar

This medium is a selective form of chocolate agar. It contains a variety of antibiotics that inhibit the growth of normal genitourinary tract microbiota but allows the growth of Neisseria species

Fecal transplant

This is a way to help treat a patient who is having recurrent episodes of C. Diff. It helps to replenish the normal microbiome Note: there are select microbes combined in pill form and swallowed too

Timeline of antibiotics

This posses a problem for antibiotic resistance! We are really only tinkering with the current treatments we have (adding side chains, etc). Once the bacteria become resistant to the current treatment, we dont have anything new to combat them!

catherized urine specimen

This technique is preferred when a patient with suspected UTI cannot urinate on their own. The urine will then drain into a sterile container. The process of catheterization can introduce bacteria and potential pathogens into the bladder.

Case History. Maria, a rambunctious 5 year old from San Francisco, was taken to the emergency department after having a severe cough for two weeks. Her illness started as a runny nose, dry cough and a low grade fever. But now the coughing comes in violent fits lasting up to one minute (called a paroxysm). Unable to breathe between coughs, the girl became cyanotic.

This telltale "whoop" indicated whooping cough, a highly contagious disease in its early stages. Cough persists for weeks from damage caused by the pertussis toxins. The resident took a nasopharyngeal swab sample for culture and prescribed azithromycin (a macrolide antibiotic which inhibits protein synthesis). A blood sample was also drawn to test for anti-Bordetella pertussis IgA antibody, positive next day. Despite extensive efforts at vaccination, over 41,000 cases of whooping cough were reported in the US in 2012 (18,000 in 2011).

Bile solubility test

This test is used to differentiate Streptococcus pneumoniae from other species of alpha- hemolytic streptococci. In this test, a sample is taken and cultured either in broth or on agar. Once cultures have grown, a bile salt is added directly to the colony, which will selectively trigger autolytic enzymes leading to lysis of Streptococcus pneumoniae . The pathogen S. pneumoniae will lyse. Normal alpha-hemolytic Gram positive cocci will not lyse.

Exogenous sources

Those external to the patient such as patient care personnel, visitors, patient care equipment, medical devices, or the healthcare environment

Nystatin

Topical antifungal

Human stages of the malaria life cycle

Transmitted by mosquitos in the form of sporozoites which injects the liver It stays in the liver phase for 7-14 days where they can differentiate into hypnozoites which lay latin for weeks to months They will travel to the blood stream where they have erythrocytic cycle where they invade RBCs and grow to asexual form Gametocytes will form which can be picked up by mosquitos

Active Transport

Transport against concentration gradient Energy required -Uniport -Symport -Antiport

Common therapy for B. anthracis (gram positive rod)

Typically susceptible to many penicillin antibiotics...But - Problem is with concerns for extended resistance of "weaponized" strains for biological warfare. So the recommendation is... -Quinolone class of antibiotics, eg ciprofloxacin or tetracycline class of antibiotics, eg doxycycline. -May need combination for serious, disseminated infections

UTI vs. C. trachomatis STI

UTI are usually accompanied with lower back pain Very rarely is there a discharge with UTIs

Case History 1: Melissa, a 25-year-old woman, visited her doctor's office complaining of a terrible burning sensation while urinating and back pain. The physician assistant suspected the patient was suffering from a urinary tract infection (UTI) in her bladder and sent a sample of urine to the laboratory. Microscopic analysis of the urine revealed presence of neutrophils and red blood cells. The laboratory took a small but exact volume of urine and spread it onto blood agar medium. After 24 h of incubation, the clinical microbiologist found large numbers of colonies corresponding to 100,000 bacteria per ml of urine. The culprit was a Gram-negative rod.

UTI caused by Escherchia coli

Possible indications for concomitant antipyretic administration and mechanical cooling in children include:

Uncertainty about the cause of elevated temperature (heat illness versus fever) Fever combined with a component of heat illness (eg, from over-wrapping, hypovolemia, or drugs such as atropine) Underlying neurologic disorder, in which the child may have abnormal temperature control and poor response to antipyretic agents

Antigenicity phenotype

Unique epitopes (OAg, HAg) Note: can use antibody profile to categorize

Obligate Intracellular bacteria phenotype

Unique growth niche (most grow in eukaryotic host cell)

ExPEC strains (Extraintestinal)

Uropathogenic E. Coli (UPEC) Neonatal Menigitis strains

Metronidazole

Used against anaerobes and parasites Inhibits nucleic acid synthesis by disrupting the DNA of microbial cells. This function only occurs when metronidazole is partially reduced, and because this reduction usually happens only in anaerobic bacteria and protozoans, it has relatively little effect upon human cells or aerobic bacteria.

High level disinfectants

Used for items involved with invasive procedures that cannot withstand sterilization procedures Ex: germicides, boiling/pasteurization, and liquid forms of H2O2, glutaraldehyde, bleach

Posaconazole

Used for resistant candida species, aspergillosis, and mucoromycosis

Intermediate level disinfectants

Used for surfaces and instruments where contamination by spores is unlikely Ex. alcohols, iodophors, and phenolics

Low level disinfectants

Used to treat non-critical items such as BP cuffs, ECG electrodes that are noninvasive Ex. quaternary ammonium compounds such as benzalkonium chloride

Oxozolidinones (Linezolid-ZYVOX)

Useful for Gram positive infections: One of the more recent new drug treatment for Staphylococcus infections Thought to attack an unexploited site: The proper assembly of the feet-tRNA with mRNA and the 30S subunit. May also act by binding 50S and preventing 70S formation

Symptoms of C. trachomatis STI

Usually occur within 1-2 weeks post infection (takes time for them to build up) Discharge and burning when urinating In women, if infection spreads to fallopian tubes, possible abdominal pain, low back pain, nausea, fever

Fungal virulence attributes

VIRULENCE IS MULTIFACTORIAL! Adherence to host tissues Invasion -Hyphal formation (must grow in tissues) -Secretion of proteinase, elastases, etc. Evasion of host response -Protection from ROS-mediated killing, physical barriers (capsule production) to inhibit phagocytic killing Immunomodulation -Skewing towards TH2 response

Reproductive Tract infection

Vaginitis (inflammation and itching of the vulva) -bacterial vaginosis, vaginal candidiasis, syphilis, Trichomonas, Chamydia, Neisseria gonorrhoeae Note: this is a mucosal infection

Prevention of malaria

Vector control (community): -Bed nets (insecticide treated) -Indoor spraying of insecticides Insect avoidance (individual): -Insect repellants -Chemoprophylaxis

R. Akari vector and reservoir

Vector- Mite Reservoir- Mite, Wild rodents

R. rickettsii vector and reservoir

Vector-tick Principal reservoir- Hard Tick -> 6 hours Can be transmitted via transovarion transmission (persists in the vector) and wild rodents Resides in Tick salivary glands

Malaria Epidemiology

Vector: Anopheles mosquitos Species: Plasmodium species P. falciparum (common and severe) P. ovale/vivax (latent phase) P. malariae Cases: >200 million/year Deaths: >600,000/year (mostly African children)

A. phagocytophilium vector and reservoir

Vector: Deer Tick (ixodes) Reservoir: Small mammals

B. bacilliformis vector and reservoir

Vector: Sandflies (in andes mountains) Reservoir: variety of animals

Rickettsia prowazekii vector and reservoirs

Vector: body louse (it infects their gut epithelial cells that slough off into feces which can be introduced to us by scratching that area) Reservoir: humans, flying squirrels Note: the louse dies with no transovarial transmission

E. Chaffeensis vector and reservoir

Vector: lone star tick Reservoir: White-tailed deer, domestic dogs Note: white tailed deer are an important reservoir since there is no or poor transovarian transmission

When is clinical microbiology lab used?

When a first antibiotic empirically prescribed as failed Note: physicians should be familiar with the lab their patients are referred to: it should have well documented quality controls, reference strains, etc so that it provides reliable results Note: it is critical to know how to collect a useful sample and the the limitations of each analysis

What is the clinical relevance of bacterial gene regulation?

Virulence gene expression is highly regulated Virulence determinats tend to be induced under stress conditions that indicate encounter with a host This helps to conserve metabolic energy and ensure that virulence determinants are only produced when their particular property is needed

Types of bacteriophage

Virulent (lytic replication) Temperate (lytic and lysogenic replication)

A healthy 34-year-old Japanese man presented with a 10-day history of epigastralgia. He had eaten seared chicken sashimi several times. Physical examination findings were not remarkable. Laboratory findings revealed marked eosinophilia (20 ×109/L). Chest CT revealed multiple nodules in the lung surrounded by a halo. Abdominal contrast-enhanced CT revealed multiple low-attenuating nodules in the liver.

Visceral larva migrans

Enterotoxigenic strains (ETEC)

Watery diarrhea

Disease/conditions caused by Escherchia coli

Watery diarrhea Bloody diarrhea Sepsis Urinary tract infection Meningitis

Enteraggregative strains (EAEC)

Watery diarrhea, brick-like form of adhesion in gut

Enteropathogenic strains (EPEC)

Watery diarrhea, pedestals

Mycobacteria phenotype

Waxy

neurocysticercosis transmission

fecal oral transmission

Bacterial colonies

We still cant culture a lot! We culture them on or in a media and their size, shape, color can help distinguish them

Lysogenic conversion

When a cell becomes lysogenized, extra genes carried by the phage can occasionally change the properties of the bacterial cell. This process is called lysogenic or phage conversion. Clinical relevance: - lysogenic phages have been shown to carry genes that can modify the Salmonella O-antigen which is one of the major antigens to which the immune response is directed. - toxin production by Corynebacterium diphtheriae is mediated by a gene carried by a phage. Only those strains that have been converted by lysogeny are pathogenic.

Is Rocky mountain spotted fever often misdiagnosed

Yes! -Rash not detected or pre-rash visit -flu like symptoms -off season -painless tick bite with no eschar

How does fungal culture help in definitive identification?

When looking at filamentous (molds): Pure culture is prepared for microscopy -Lactophenol cotton blue (LPCB) tease mount: allows you to see hyphae morphology, conidia/sporangia When looking at yeast: Microscopy can be coupled with biochemical tests (Germ tube test, CHROMagar, Urease, Carb assimilation)

Obligate intracellular pathogens

Will grow only inside host cells Rely on the host cell for supplies Will NOT grow on artificial media Rickettsia, Coxiella, Chlamydia, Anaplasma

Are all infectious diseases known to us?

With all that we know about infectious diseases, we will never know enough because new diseases are continually emerging or reemerging. Reemerging diseases are diseases that have been around but are now rapidly increasing in incidence, geographic range, or both

In bacteria, is transcription and translation coupled in time and pace?

Yes! There is no nucleus, so as soon as a mRNA transcript is generated in the cytoplasm, ribosomes attach and initiate translation

Are women infected with Trichomonas vaginalis more at risk for delivering baby pre-term and low birth weight babies?

YES

Can a changing microbiota can alter our susceptibility to pathogens, the development of our immune system, and, our weight?

YES

Can animals and insect reservoirs also function as "incubators" for new infectious diseases yet to emerge in humans?

YES

Can miscarriage be viewed as a host defense strategy to eliminate a nidus infection?

YES

Can some parasites convert one type of host to another?

YES

Do many classes of antibiotics have cross activity between the different types of pathogens?

YES

Do some parasites use more than 1 host?

YES

Does the treatment for hyperthermia and fever differ?

YES

Does the use of disinfectants select for the the genetically linked antibiotic resistance genes?

YES

In chaga disease, do manifestations of the acute disease resolve spontaneously in about 90% of infected individuals even if the infection is not treated with trypanocidal drugs?

YES

Is Coxiella burnetii a select agent?

YES

Is WHO on track to meet its goals to control, eliminate, or eradicate sleeping sickness, Chagas, and other ancient illnesses by 2020?

YES

Is the exact sequence of amino acids in a protein specified by the sequence of nucleotides found in the mRNA transcripts?

YES

Should the whole family be treated at the same time as a child being treated for pin worm?

YES

Should you know local susceptibility trends and also surveillance limitations?

YES

Can even a simple infection cycle become complex?

YES For example, rhinovirus can be spread person-to-person by a sneeze (air- borne) or through the sharing of inanimate objects (fomites) such as contaminated utensils (fork, pen), towels, cloth handkerchiefs, and doorknobs. Handshaking is also an efficient means of transferring some pathogens. Imagine that one woman in a city of 100,000 people has a cold and sneezes on her hands. Then, without washing her hands, she goes through the day shaking hands with ten people, and each of those people shakes hands with another ten people per day, and so on. If no repeat handshakes take place and if none of the contacts washes his or her hands, the virus will spread throughout the population in only 4 days. In this example, eventually the entire populace of the city comes in contact with the virus, but not everyone actually con- tracts disease. Additional factors, such as the effectiveness of the host's immune system, influence whether the virus successfully replicates in a given individual. Sometimes the infected host can become a carrier

Do microbiota and host cells carry on chemical conversations?

YES Host cells signal to the microbiota via hormones Microbial products such as butyrate, indole, and others are sensed by the host cells causing it to alter its gene expression

Does mycobacterium tuberculosis often have mutations in multiple, independent targets that confer resistance to many different drugs?

YES MDR-TB is multi drug resistant XDR-TB is extensively drug resistant! TB is one of the most common infections world wide and getting more difficult to treat

Are there neglected parasitic diseases in the U.S.?

YES Mainly: -chagas disease -cysticerosis -toxocariasis -toxoplasmosis -trichomoniasis

Are most worm infections asymptomatic?

YES Note: 1.5 billion people are infected by helminths worldwide

Is resistance a serious problem?

YES People infected with resistant bacteria are more likely to have longer hospital stays and require treatment with second or third-choice medicines that may be less effective, more toxic and more expensive. Estimated Additional Healthcare Costs of $20 billion

Is precise targeting better than shotgun therapy?

YES Physicians must know the prevalent pathogens for each kind of infection, and the local susceptibility trends. Despite the many different bacteria that cause infections in humans, in the outpatient setting there is only a handful of relent organisms Narrow spectrum drugs should be preferred when possible: wide spectrum is only necessary when potential causative pathogens are very diverse or when the infection is potential polymicrobial

Should you use the shortest anybody course that has proven clinical efficacy?

YES Physicians must review available data on PK/PD in order to adequately select drugs and dosing and to prevent resistance

Is Rickettsia prowazekii a select agent?

YES Possible to weaponize

Do new genotypes arise when genetic material is transferred from one bacterium to another?

YES Transferred DNA either recombines with the genome of the recipient cell or replicates autonomously as a plasmid Recombination can bring about large changes in the genetic material and since these events usually involve functional genes, they are likely to be expressed phenotypically

Can you culture candidia?

YES Yeast cells with single buds only Routine culture and sensitivity: Candida will grow on Sheep Blood Agar (SBA) within 24 hr forming a "staph-like" colony Fungal culture: SDA positive within 48-72 hr

Are at least half of prescribed antibiotics not necessary or otherwise abused?

YES ex. 50-80% of patients displaying viral symptoms receive them (a particular cat is pharyngitis where at least 80% of cases have a viral etiology) ex. Otitis media (in children w/o high fever or vomiting) is another abuse example when supportive measures work best Note: should give in fever without signs and symptoms of infection and self limiting bacterial infection such as many diarrheal diseases, and asymptomatic bacteriuria except during pregnancy

Do salmonella produce H2S on Hektoen?

YES (therefore they will appear black)

Can the C. trachomatis D-K serotypes also cause Adult/Infant Conjunctivitis and Infant pneumonia?

YES! Adult --> oral/ocular-genital contact (dirty towel), autoinoculation Infant --> contracted during birth from infected mother Note: ~25% will progress to infant pneumonia if not properly treated Should be treated with Erythromycin for 10-14 days

Is the human microbiome a complex and dynamic population that changes in response to environmental stimuli?

YES, it can change in response to: Changes in sanitation/hygine practices (when we become more civilized- Hygiene hypothesis) Stress Changes in diet Antibiotic treatment (disrupt balance of power in the gut)

Is fungal morphology important?

YES, it is intimately tide to invasive disease The shape of fungal cells in culture is used to support definitive diagnosis of fungal infections (this has been supplemented in recent years with serological and nucleic acid based tests)

Are intracellular pathogens protected from immune responses?

Yes

Do host-microbe interactions tread a fine line?

Yes Benign-> Neither host or microbe get a benefit Beneficial-> Both benefit from the relationship Deleterious-> These harm

Can we expect global warming to change worldwide disease patterns?

Yes For instance, as a result of rising global tempera- tures, insect vectors now limited to tropical areas of the world will be able to migrate to higher (historically colder) latitudes, bring- ing infectious microbes with them. All this stirring up of the global environment not only fosters the spread of existing diseases but also builds breeding grounds in which new pathogens will evolve

Can many bacteria synthesize their own metabolic precursors de novo?

Yes From simple organics, inorganic, and energy sources (they can basically grow on rocks)

Does african trypanosomiasis have mechanism for antigenic variation?

Yes They express a surface protein called VSG (variant surface glycoprotein) which is made up of a lot of genes and has the ability to undergo recombination in response to the immune system

Are glycocalyx important for virulence

Yes They prevent penetration of antimicrobial compounds and prevent phagocytosis by host immune cells

Can bacteria recognizes human hormones?

Yes ex. Staphylococcus epidermidis responds to norepinephrine

Can plasmids carry virulence genes?

Yes (acquisition of pathogenicity islands) They may encode for toxins and other proteins that increase the virulence of microorganisms. For example, - Virulent enterotoxinogenic strains of Escherichia coli that cause diarrhea express plasmid-encoded enterotoxins. - Staphylococcus aureus expresses a number of plasmid-encoded virulence determinants such as an enterotoxin, hemolysin and fibrinolysin. - Yersinia pestis expresses a plasmid-encoded phospholipase D that is important for the transmission of the organism from fleas to mammals.

May plasmids carry genes?

Yes (up to 100 on larger plasmids) which can confer phenotypic advantages to the host bacterial cell

Should antibiotic courses be shortened?

Yes If possible The physical should rely on publications for this information

Does Coxiella burnetii use antigenic phase variation?

Yes based on LPS antigen Phase I is associated with the highly infectious form Phase II is less infectious This helps in immune avoidance

Is there an increase incidence in human mycoses?

Yes in part due to: Aggressive chemotherapy Better diagnosis

Are antibiotics are limited?

Yes they are non-renewable resources that we all need during our lives

Can staphylococcus aureus disseminate for the primary infection?

Yes, it can produce metastatic lesions (including osteomyelitis which would require direct injection of antibiotics via pic line)

Do some Escherchia coli invade intestinal epithelial cells?

Yes, some do not though (depends on virulence factors)

Can 99% of our microbiota not be cultured?

Yes, their growth requirements and patterns are such that we cant grow them on currently used media We know this thanks to the Human Microbiome project. This used culture independent analysis and sequenced all the DNA in the sample (metagenomics). This showed thousands of different species

May people with cholerae exhibit dehydration?

Yes, they can loose liters of fluids per day In fact, dehydration is a common consequence of diarrhea in general

Does bacterial fermentation have a practical component to it?

Yes, they help in making food and other products needed current economics

Does the microbiota train the host immune system?

Yes, they interact with Peyer's patch M cells to train B and T cells via cytokine milieu telling the T cells what to do Microbiome helps keep the balance of T cells just right Germ-free animals have imbalance in Th1/Th2 cell profile and reduced CD4+ T cell population. Colonization by a single bacterium can restore balance. Not just any gut microbiome will do! Human GI microbiome will not help gnotobiotic mouse.

Do both facultative and obligate intracellular pathogens benefit from the anti fo binding inside host cells?

Yes, this helps hide them from the host immune system

May taeniasis be asymptomatic?

Yes, with sompontaneous realse of proglottids for T. saginata Associated symptoms nonspecific: -Weight loss, abdominal pain, vomiting, diarrhea, constipation, altered appetite

Does syphilis have stages?

Yes; Primary, secondary, and tertiary The disease becomes more severe with each stage

Common therapy for Y. enterocolitica (gram negative rod)

Zoonosis - Antibiotic therapy has not been shown to have much effect - For sepsis, especially in infants ~Combination therapy of 3rd generation cephalosporin, eg ceftriaxone, plus an aminoglycoside, eg., gentamicin is often used Problem with the development of resistance

mortality

a measure of how many patients have died from a disease

Organ

a relatively independent part of the body that carries out one or more special functions

Multiplex polymerase chain reaction (PCR)

a variation of PCR. PCR is a molecular biology technique used to amplify a DNA sequence. A thermocycler changes temperatures to favor different steps of the PCR process: denaturation of double-stranded DNA(dsDNA), annealing of primer to single-stranded DNA(ssDNA), and elongation of new DNA strands, which is complementary to template DNA strands. In multiplex PCR, multiple primer sets are used simultaneously to amplify multiple DNA sequences in one PCR assay. Using this procedure a clinical specimen can be screened for multiple bacterial pathogens in a single reaction. An advantage of this technique is time. Identifications based on bacterial culture and biochemistry can take 24 to 48 hours. PCR will take a matter of hours and can be done directly from the specimen. Cost, however, is a limiting factor. When performing multiplex PCR, it is essential to select the appropriate primer for each specific DNA sequence so that they are compatible with cycling temperatures as well as other primers used.

IBS (irritable bowel syndrome)

abdominal pain and cramping, changes in bowel movements, and other symptoms. IBS is not the same as inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis. In IBS, the structure of the bowel is not abnormal.

trophozoites

active, feeding protozoa

Glutaraldehdye MOA

alkylation induced damage of proteins/nucleic acids

Ortho-phthalaldehyde MOA

alkylation induced damage of proteins/nucleic acids

Griffith's experiment

an experiment carried out by Griffith using the heat-killed bacteria in mice to discover that a factor in heat-killed, disease-causing bacteria can "transform" harmless bacteria into ones that can cause disease

_____ make up the vast majority of microbiome in the intestines

anaerobes

Management of Heliobacter pylori infections require___

antibiotic combinations

Nonpilus Adhesins

are bacterial surface proteins or carbohydrates that can tighten interactions between bacteria and target cell's proteins and carbs.

When does translation begin and end?

begins with formation of an initiation complex and terminates at a stop codon

All antibiotics affecting cell wall biosynthesis are usually _______ and all require _____

bactericidal; Growth Note: on graph, there will usually be an uptick in growth because the bacteria will grow and remodel their cell wall and in the process their cell wall be become weakened. They will then be susceptible to turgor pressure and pop

Decline phase

begins as the symptoms subside. Host defenses have won. As the infection recedes, fewer pyrogens (the compounds that trigger fever) are made and the thermostat is reset to the lower temperature. To restore body temperature, blood vessels will dilate to lose heat (vasodilation), and the patient will start to sweat. These are the signs of "breaking a fever."

invasive phase

begins when typical symptoms and signs of the disease appear. (Do not confuse the invasive phase of a disease with the invasiveness of a pathogen.)

Candidiasis speciation is achieved via_____

biochemical and selective agar CHROMagar generates Candida colonies with species-specific colors Germ tube test - C. albicans will form germ tubes (the beginning of true hyphal development) under specific culture conditions Sugar assimilation tests and the differentiation of developmental structures in culture are also used for speciation of Candida

neurocysticercosis definitive diagnosis

biopsy, autopsy, neuroimaging Note serological test support the diagnosis but cannot differentiate between active and past infections

There is a high and disproportionate burden of urinary Trichomonas vaginalis infection in the adult civilian, noninstitutionalized _______ in the United States that warrants intervention.

black population

Endogenous sources

body sites, such as skin, nose, mouth, GI, or vagina that are normally inhabited by microorganisms

Amoxicillin

broad spectrum penicillin

Ampicillin

broad spectrum penicillin

What temps do listeria grow

broad temp range, including refrigeration temps

two components of the ETC

change in pH, where H+ ions are pumped across the membrane Charge difference, the H+ ions carry a charge and produce a difference across the membrane This helps power complex 5 and generates ATP

Turbidity

cloudiness, you are looking at the density of a culture using a spectrometer to measure this density and as density increases, the number of bugs increases as well Note: the density doesnt depend on dead vs. live, it just includes everything in that culture

MRSA (methicillin-resistant Staphylococcus aureus)

common in community and hospital environments Resistant to Methicillin, oxacillin, and nafcillin Will often require vancomycin

R1 plasmid

confers resistance to ampicillin, chloramphenicol, fusidic acid, kanamycin, streptomycin, and sulfonamides

Does Aspergillus aerial hyphae produce conidia or spores?

conidia

Does Fusarium aerial hyphae produce conidia or spores?

conidia

Preventative measures for malaria

consists of a combination of mosquito avoidance measures and chemoprophylaxis For areas of intense transmission, such as West Africa, exposure for even short periods of time can result in transmission, so travelers to this area should be considered high risk. Malaria transmission is not distributed homogeneously throughout all countries. The highest risk is associated with first- and second-generation immigrants living in nonendemic countries who return to their countries of origin to visit friends and relatives (VFRs). Acquired resistance is lost quickly and preventative measures are needed. Use screened areas (nets, etc) during dusk to dawn, pyrethroid containing insect spray, and wear long clothes Note: sunscreen first, then repellent Take chemoprophylaxis before, during, and after travel. Presumptive anti-relapse therapy is generally indicated for people with prolonged exposure to malaria endemic areas.

Fecal - Oral protozoans form ____ to resist external environment

cysts

Invasion

describes the ability of some pathogens to actually enter (invade) and live inside a host human or nonhuman animal cell.

The first step in the management of fever is to ___

determine its cause Once cause is known, the main reason to treat fever is to improve the childs comfort

acquired immunity to malaria

develops after long exposure and is characterized by low levels of parasitemia. Immune individuals have intermittent parasitemia with only mild symptoms. This state has been referred to as premonition, in contrast with classic immunity, which prevents any degree of infection.

L. monocytogenes causing gastroenteritis

develops within 48 h of ingestion of a large inoculum L. monocytogenes is neither sought nor found in routine fecal cultures Clinically, Listeria is not often recognized as the cause of diarrhea because in immunocompent people the diarrhea is mild and resolves quickly.

tra genes

encode for factors necessary to transfer the plasmid DNA from the donor cell to the recipient cell. They also encode for products required to synthesize the sex pilus which is used to form the mating bridge

Carbenicillin

extended spectrum penicillin (eg. pseudomonas which is known to be a very antibiotic resistant bug)

pathogenicity islands

foreign DNA that is introduced into bacterial chromosome and it contains genes for virulence

Bacterial numbers increase in ___

geometric progression and their population doubles every generation time Note: can be as fast as 20 mins in E. Coli growing in a rich medium Note: no new genetic

Global increases in death and disease are often connected to ___

human activities that bring humans closer to disease reservoirs and vectors

MOA of H2O2

hydroxyl radicals damage lipids, DNA, proteins

MOA of plasma gas

hydroxyl radicals damage lipids, DNA, proteins

Vectors can be _______ hosts

intermediate and/or definitive

A 3-year-old girl arrived at emergency department with abdominal pain and diarrhea for the last 3 days. The previous day she took an unspecified anthelmintic. Symptoms worsened with vomiting and diarrhea, with expulsion of roundworms through mouth and anus. Physical examination revealed bloating, absence of bowel sounds, abdominal tenderness, and a palpable mass in right hemi-abdomen.

intestinal obstruction (IO) by Ascaris lumbricoides infestation

Internalin mediated entry is important in the crossing of___

intestinal, blood-brain, and fetoplacental barriers

Fungemia

invasive disease with potential multisystem involvement

virulence

measure of the degree or severity of disease Can measure via lethal dose

Beta-lactamase inhibitors

medications combined with certain penicillin drugs to block the effect of beta-lactamase enzymes Includes clavulanic acid, tazobactam, sulbactam

Is Enterococcus faecalis catalase negative or positive

negative

Is strepococcus pneumoniae catalase negative or positive

negative

Is strepococcus pyogenes catalase negative or positive

negative

Nutrition and exercise effect on infection susceptibility

nutrition and moderate exercise can enhance a person's immune system.

Droplet transmission

occurs upon exposure to respiratory droplets carrying pathogens directly from the respiratory tract of the infectious individual to susceptible mucosal surfaces of the recipient (usually over short distances; e.g. influenza virus)

Ear infections

otitis externa otitis media otitis interna

Fleming, Florey, and Chain

penicillin

What color is gram negative

pink

Is staphylococcus aureus coagulase positive or negative?

positive

Transcriptional activators

positive regulation, increase the rate of transcriptional initiation They can attract RNAP to bind more efficiently

toxemia

presence of toxins in the blood Diphtheria, toxic shock syndrome

viremia

presence of viruses in the blood HIV

Peracetic acid MOA

production of reactive radicals damage lipids

pathophysiology of malaria

rupture of RBC releases pyrogens that stimulate episodic fevers and sweating with falciparum, anemia caused by hemolysis can be severe. The kidneys also show punctate hemorrhages and even tubular necrosis. This can lead to hemoglobin in the tubules and causes hemoglobinuria and is complicated with therapy with quinine with vicvx, spleen can become acutely enlarged and is susceptible to rupture chronic infection with malaria cues persistent splenomegaly Pigment collects in the spleen and causes its darkening Congenital can develop with any species They tend to suppress cell mediated immune responses

Toxoplasmosis has been linked to _____

schizophrenia, depression, autism and even an increased risk of being involved in traffic accidents. Note: ex. parasite makes mice lose fear of cats permanently

Electron transport system

second step in areobic metabolism in mitochondria, which makes 90% of body energy and uses O2; aka repiratory chain

Pili

short, hairlike protein structures on the surface of some bacteria There are attachment tip on them that allows them to noncovalently adhere to host proteins and allow them to stick

symptom

something that can be felt only by the patient, such as pain or general discomfort (malaise).

Sign

something that can be observed by a person examining the patient—for instance, a runny nose or a rash.

Interdomain metabolic collaboration

species from different domains collaborate with each other (microbiota and humans communicate back and forth to each other; and microbiota communicates with archaea) They basically produce end products that are used by another organism Ex. The presence of H2 oxidizing methanogens in the human intestine removes H2 produced by bacterial fermentation. The reduction of H2 levels is thought to relieve H2 endproduct inhibition of fermentation by bacteria.

Regulatory proteins bind ____

specific DNA sequences known as operators or operator sites (also known as regulatory DNA regions) Includes: Repressors: inhibit transcription Activators: increase the rate of transcriptional initiation Note: Regulatory DNA regions can be found upstream, downstream, and within genes (coding regions)

In the absence of Lactose, LacI binds _____

specifically to the lac operator of the lac promoter and blocks transcription

Spirillum

spiral rod shaped bacteria morphology

Selective growth media

suppress growth of unwanted species and encourage growth of other species

cysticerosis

systemic infection that results from consumption of infected pork, vegetables, or water contaminated with eggs of the helminth Taenia solium pleomorphic in nature and is characterised by a latent phase that can last months to years after exposure

diauxic growth

the biphasic curve of a culture growing on two carbon sources

The duration of administration of antipyretic therapy depends upon___

the childs response

Deep abscess aspiration

the drainage of an enclosed, pyogenic (pus-containing) collection of fluid. Needle aspiration rather than swabs are preferred because anaerobic bacteria can be the cause of these infections. The procedure can be performed in abscesses located in the thoracic, abdominal, or pelvic cavity, as well as deep tissue (i.e. thigh, axilla, subperiosteal, etc.). A catheter or needle is guided into the abscess by CT or ultrasound imaging, and a sample of fluid is collected. If the abscess is to be drained a specific drainage catheter is placed into the abscess cavity using a guided wire and allowed to empty.

Morbidity

the existence of a disease state and the rate of incidence of the disease. You do not have to die to be included in a morbidity statistic, only sick

Infectious dose

the number of microorganisms or viruses sufficient to establish an infection A critical component of a microbes ability to initiate infection

Catabolite repression

the suppression of alternative catabolic pathways by a preferred source of carbon and energy (such as preferred use of glucose suppressing the lac operon)

incubation period

the time after a microbe first infects a person through a portal of entry (discussed shortly) but before the first signs of disease.

Exotoxins

toxic substances that bacteria secrete into their environment that have deleterious effects on the host

External cooling

treatment of choice for heat stroke and other forms of heat illness in which rapid cooling is necessary to prevent end-organ damage Not recommended for fever, but can be used as an adduct for greater reduction than the antipyretic alone Note: sponging is more effective and comfortable than immersion

Dilution Test

used to determine the MIC by looking at the turbidity of the culture There will be serial dilution of the antibiotic and the growth is observed at the different concentrations

Lumbar puncture

used to obtain cerebral spinal fluid (CSF) to check for a meningeal infection or a subarachnoid hemorrhage. CSF should normally appear clear and is sterile. If it is cloudy, it indicates an infection; red indicates a bleed To perform an LP, the patient is positioned on their side, and asked to assume a "fetal"position. This helps to open up the intervertebral spaces, so that the needle can pass more easily. Ideally, the needle is inserted somewhere between L3 and L5. This is below the conus medullaris (L2), the spinal cord continues on only as the cauda equine whose fibers will move out of the way as the needle is inserted First pop is the ligamentum flavum and the second pop is the dura mater

For community acquired infections, the best drug for the job is ____

usually a single one, not combined

____ reduce disease prevalence and antibiotic demand

vaccines

Malaria species preferentially invade:

vivax and ovale- reticulocytes malariae- older RBCs falciparum- RBCs of all ages (high level of parasitemia)

host ranges

which animals they can infect and produce disease Note: different microbes have different host ranges!

pandemic

worldwide epidemic Note: although many microbes can cause epidemics, surprisingly few have proved capable of causing pandemics and those that do most readily accomplish this by becoming airborne

Should antibiotic dosing be adjusted for weight

yes, to avoid prescribing too little or too much of a drug

What is the result of a blood agar culturing staphylococcus aureus

ß hemolysis

What is the result of a blood agar culturing staphylococcus pyogenes

ß hemolysis

Methicillin

ß lactamase resistant- Acid labile (should be given IV) Narrow spectrum

Oxacillin

ß lactamase resistant- Acid stable (can be given well orally) Narrow spectrum

What is a PAMP for fungal pathogens

ß-(1,3)-glucan is an important component for immune recognition!

An essential determinant of the pathogenesis of L. monocytogenes is its__

ß-hemolysin, listeriolysin O (LLO) It is responsible for mediating the rupture of the phagosomal membrane that forms after phagocytosis Mutations in LLO that influence its synthesis, cytosolic half-life, or pH optimum cause premature toxicity to infected cells

Lysozymes break____

ß1-4 linkages The net result is disruption of the cell wall, making bacteria susceptible to lysis by osmotic stress Note: these are in tears!

Microbes vary greatly in their:

1. Ability to assimilate different carbon, nitrogen, etc sources 2. Ability to grow in the presence/absence of O2 3. Metabolic end-product generation 4. Mechanisms of motility (some don't swim at all) These difference are used diagnostically to differentiate one microbe from another

Gram negative cross linking: Transpeptidation

A covalent bond between between adjacent polymers DAP and D-Ala is formed to increase strength The D-Ala - D-Ala bond is broken to supply energy for crosslinking and the covalent bond is formed between polymer

Gram staining

A differential staining technique 1. Fix to glass slide so they won't wash off the slide 2. Add crystal violet 3. Add iodine which forms a larger complex with crystal violet within the cell 4. Decolorize with alcohol and wash. The structure of gram negative membrane allow the crystal violet:iodine complex to be washed out 5. Add the counter stain, Safranin, which can enter the gram neg and make them appear pink

MacConkey Agar

A selective and differential agar. Contains bile salts and dyes which allow for the selection of gram negative organisms Contains a complex mixture of digested peptides which provides aminos acids for the growth of the bacteria. There is also a carbon source, lactose. Depending on what they grow on and their end products, they can cause a color shift in the indicator dye Red-Acidic Yellow- Alkaline

Pili are used for:

Adhesion Twitching motility Conjugation (bacterial sex)

Biofilms are used for__

Adhesion to surfaces Community growth Resistance to disinfectants and antimicrobials

Allele

An alternate form of a gene possessed by a particular organism

What is the importance of bacterial genetics

Bacteria are amenable to genetic manipulation and are useful model systems for studying fundamental biological processes. Genetic approaches are important for understanding how pathogenic bacteria cause disease, evade host immune responses and develop resistance to antibiotics. Genetics facilitates the development of novel biotechnologies (e.g., CRISPR-Cas gene editing). Genetics provides the basis for many state-of-the-art diagnostic assays and epidemiological tools.

Bioflims

Bacteria can grow as individuals or in communities called biofilms They secrete a polysaccharide that effectively allows the bacteria to aggregate

Bacteria divide by ___

Binary fission (one bacterium splits into two, asexual replication) Note: no new genetic information is introduced

Actinomycetes phenotype

Buds and protuberance

General cytoplasmic membrane structure

Cell membranes consists primarily of a thin layer of amphipathic phospholipids which spontaneously arrange so that the hydrophobic "tail" regions are shielded from the surrounding polar fluid, causing the more hydrophilic "head" regions to associate with the cytosolic and extracellular faces of the resulting bilayer. Forms a continuous, spherical lipid bilayer

Central Dogma

DNA is transcribed to RNA which is translated to protein

Bacteria Cytosol is the site of:

DNA replication (DNA gyrase helps unwind) Transcription (Unique RNA Pol) Translation (70s ribosome compared to the 80s of eukaryotes) Metabolism (folate biosynthesis)

How do we distinguish a pathogen from normal flora in a patient diagnostic specimen?

Dilution streaking technique Normally your sample will contain a lot of different bacteria mixed in (unless a urine, then it is usually enriched in the causative agent)

Lipid A=

Endotoxin Can Kill via a cytokine storm and thus shock

Peptidoglycan as an antimicrobial target

Excellent target seeing as we dont have this! -Autolysins: hydrolyze ß1-4 (produced by the bacteria, used for remodeling) -Penicillins: block transpeptidationeventually causing lysis due to turgor pressure -Bacitracin: block bactoprenol eventually causing lysis due to turgor pressure

Sporulation

Gram positive species like Bacillus anthracis and Clostridium spp. go through this differentiation called sporulation Things get really bad so they form a spore which packages all nucleic acid and important proteins and are covered in rigid stuff like dipicolinic acid This produces a stable, inert form of the microbe waiting for conditions to improve Note: most gram negative cant do this

E. Coli: MacConkey

Grows- Gram Negative Red- Contains beta galatcidase which allows for the metabolization of lactose. The lactose will be further metabolized and the end products are acidic (therefore it is a fermentor)

Enterobacter aerogenes: MacConkey

Grows- Gram Negative Red- Contains beta galatcidase which allows for the metabolization of lactose. The lactose will be further metabolized and the end products are acidic (therefore it is a fermentor)

Proteus Vulgaris: MacConkey

Grows- gram negative Yellow- Grows on the peptides and the byproducts of this slightly alkalinize the media (therefore they are nonfermentor)

Salmonella Typhimurium: MacConkey

Grows- gram negative Yellow- Grows on the peptides and the byproducts of this slightly alkalinize the media (therefore they are nonfermentor)

Type three secretion system

Hollow tubular structures made of protein that cross the G negative inner and outer membrane and penetrate host cell membrane (syringe) Function to translocate 'virulence effector proteins' made in the bacterial cytoplasm into the host cell's cytoplasm Important for virulence

Flagella (H antigen)

Hollow tubular structures made up of protein that cross the inner (and G negative outer) membrane and project out form the bacteria Act as 'propeller' that move the cell (bacteria can have one or many that work together to direct movement) Note: not all bacteria produce the same flagellar protein, so we can use it to differentiate

Pentapeptide found in Gram positive

L-Ala - D-Glu - L-Lys - D-Ala - D-Ala

Bacterial growth curve

Lag phase: Number of cells constant while cells detoxify medium; turn on new enzymes and increase in size for division Log phase: exponential growth Stationary phase: Nutrients being used up; toxic byproducts increase. New cell= Cells dying Death phase: logarithmic decline Note: this growth is predictable

How are bacteria cultured in the diagnostic laboratory

Liquid growth medium (grow as suspension) Solid growth medium (liquid medium with solidify agent)

Gram-positive phenotype

Membrane-Wall Note: based on staining and microscopy

Group translocation

Molecule is chemically modified during transport

Lipopolysaccharide (LPS)

Molecule that makes up the outer layer of the outer membrane of Gram-negative bacteria Greasy component is made from Lipid A Sugar component is made up of the core from KDO which is an 8 carbon sugar Outer most region is made up of O-antigen which is different among each bacteria and help to give bacteria their differentiation Also has porin which allows molecules to move into the periplasmic space Note: LPS is recognized by TLR4

Facilitated Diffusion

Moves large charged molecules Needs transport proteins Uses concentration gradient

Which sugar is the peptidoglycan pentapeptide attached to?

NAM

Can protein be back-translated to RNA or DNA?

NO

Mycoplasma phenotype

No cell wall

Peptidoglycan structure unit

Sugars are stuck together via a ß1-4 linkage (transglycosylation)

Heredity

The transmission of qualities from an ancestor to a descendent

Energy Coupling

The use of the proton gradient to run flagella, active transport, or microbes can ferment it

How do bacteria acquire nutrients from the environment?

They put proteins in the membrane that allows for transport There a some molecules that dont need proteins to pass

Pili (Fimbriae)

Thin tubes made of protein that extend from bacterial membrane Possess a protein at the tips that is involved in attachment to a surface (e.g. host cell)

Are fermentation products diagnostic?

YES Phenol red test turns yellow under acidic conditions. This also has a tube in the inside that can trap gas Sorbitol MacConkey agar distinguishes pathogenic E. coli from nonpathogenic E. coli

Does active transport create an osmotic problem?

Yes It allows bacteria to move substrate from a low concentration to a high concentration This high concentration inside the cell causes to be displaced and form a high concentration of water outside the cell The water will follow the gradient and rush in the cell! However, peptidoglycan helps prevent lysis!

Can microorganisms run an ETS in the absence of O2?

Yes Bacteria can use alternate electron acceptors that are nitrogen containing compounds that accepts electrons

Can bacteria do anerobic metabolism?

Yes which leads to fermentation Pyruvate can be used to create lactate and regenerate NAD+. Note, this is common between microbes and us Pyruvate can be used to create ethanol via ACDH and ADH and regenerates NAD+ in the process Pyruvate can be used to create H2 via FDH and HYD and regenerates NAD+ in the process

Gene

a region of DNA encoding a particular polypeptide chain or functional RNA such as rRNA or tRNA

Genetics

the study of genes including the structure of genetic materials, what information is stored in the genes, how the genes are expressed and how the genetic information is transferred. Genetics is also the study of heredity and variation.