Bacterial and Atypical Infections & Antibiotics

Mycobacterium Marinum

Skin Infections! Mycobacterium Marinum: Free-living bacterium Causes opportunistic infections in humans Disease known as aquarium granuloma which typically affects individuals who work with fish or keep home aquariums Salt water and fresh water or Swimming pool exposure to non chlorinated water Nodular skin lesions Tx: Abx

Pneumococcal Meningitis

Strep pneumoniae Causes: CSF leak, pneumonia, sinusitis, head trauma S&S: Fever, headache, meningisimus (neck stiff w forward/backward movement), AMS, NO RASH Dx: Lumbar puncture Tx: 3rd gen cephs, vanc

Strep Skin infection

Strep pyogenes Strep IS NOT normal skin flora, so infections are secondary to colonization. Strep spreads through the tissues, whereas staph is localized. Dx: Wound/Blood cultures-> + for group A strep. Tx: Abx (PCN, keflex, clinda)

Treponema pallidum

Syphilis This bacteria can affect almost any organ or tissue. Transmission occurs most frequently during sexual contact There has been a rising incidence of the disease in urban areas in adolescents and young adults & Injection drug users. There are 3 stages: primary, secondary, tertiary

Legionella pneumophila

"Legionnaire's Disease" Gram negative, Rod, Aerobic, Flagellated Associated with Environmental Water sources S&S: Nonproductive cough, Confusion, N/V/D, Fever Dx: Leukocytosis, hyponatremia, Increased LFTs, CXR: (Focal patchy infiltrates), Culture: Chocolate Agar Tx: Antibiotics

Francisella tularensis

Tularemia / "Rabbit fever" Gram-negative, Rod-shaped Coccobacillus , aerobic Typically spread by ticks, deer flies, or contact with infected animals Reservoir: Rabbits, Beavers, Hamsters S&S: Ulcer or papule at site of penetration, High fever (104), Nausea, malaise, headache, PNA Dx: Blood cultures, Serum antibodies rise in 2nd week Tx: Abx

Prophylaxis for Infective Endocarditis

Use Amoxicillin (keflex, clinda, azithro if PCN allergy) when: 1. Prosthetic Heart Valve 2. Previous history of endocarditis 3. Congenital heart disease 4. Unrepaired cyanotic heart disease 5. Palliative shunts and conduits 6. Valve disease after heart transplant 7. Repair with prosthetic material or device 6 months after intervention 8. Dental procedure that involves mucosal bleeding 9. Bronchoscopy-respiratory mucosa 10. Procedure of the GI or GU track (cystoscope) 11. Procedure on infected skin, skin structure or musculoskeletal (skin or muscle biopsy) 12. Surgery to replace prosthetic heart valve or intracardiac implants (AICD/Pacemakers)

Treatment of Infective Endocarditis

Based on culture results Usually, 4-6 weeks of antibiotics and then re-evaluation Consider surgery of valve if no improvement with treatment

Bactericidal

Beta-lactams, vancomycin, fluoroquinolones, metronidazole, daptomycin Kills the bacteria...you do not always have to kill a bacteria to treat the illness

Clostridium Difficile

Causes life threatening diarrhea!!! Usually caused by abx use bc it kills the good bacteria. Occurs mostly in: People > 65 who take abx and receive medical care, people staying in hospitals/nursing homes for a long time, people with weakened immune systems or previous infection with C. diff S&S: might start within a few days OR several weeks after you begin taking antibiotics ->Diarrhea: loose, watery stools for several days ->Fever, Stomach tenderness, Loss of appetite, Nausea *SPREADS from person to person VERY EASY -->Hand sanny does not kill the spores of this...must wash hands.

4th Gen Cephalosporins

Cefepime (Maxipime) (iv) Spectrum of activity: very broad->Gram-positives: similar to ceftriaxone ->Gram-negatives: similar to ceftazidime, including Pseudomonas aeruginosa Indications: nosocomial infections

5th Gen Cephalosporins

Ceftaroline (Teflaro) (iv) Spectrum of activity: very broad ->Gram-positives and gram-negatives Only approved cephalosporin to cover MRSA -backup to Vanc Indications: alternative agent for severe MRSA infections

3rd Gen Cepahlosporins

Ceftriaxone (Rocephin) (iv), cefdinir (Omnicef) (po), cefixime (Suprax) (po), Cetazidime (Fortaz) (iv), cefpodoxime (Vantin) (po) Spectrum of activity: broad->Gram-positive and Gram-negative Ceftriaxone has the best activity against gram positive aerobes, including pen-resistant S. pneumoniae Ceftazidime covers Pseudomonas Ceftriaxone is preferred therapy for inpatient empiric UTI Indications: Ceftriaxone: meningitis, community-acquired pneumonia (CAP), UTI, severe strep infections Ceftazidime: nosocomial infections Cefdinir (Omnicef) (po), cefixime (Suprax) (po), cefpodoxime (Vantin) (po): UTI, CAP

2nd Gen Cephalosporins

Cefuroxime (iv,po), cefoxitin (iv) Spectrum of activity: narrow->Gram-positive and gram-negative Several second generation agents have activity against anaerobes (cefoxitin, cefotetan, and cefmetazole) Indications: UTIs, Community Acquired Pneumonia (cefuroxime), surgical prophylaxis

1st Gen Cephalosporins

Cephalexin (Keflex) (po), cefazolin (Ancef) (iv) Spectrum of activity: narrow->MSSA, strep, and little gram-negative Cefazolin is also a drug of choice for severe MSSA infections Indications: skin and soft tissue infections, strep throat, severe MSSA infections, UTIs (if proven susceptible)

Bacterium Corynebacterium diphtheriae

Diphtheria Club shaped, leather rod. Gram positive. Aerobic. Humans are the ONLY natural host. Transmission via inhalation or open skin. S&S: URI, Sore throat, Nasal discharge, Malaise, Sheet of thick, gray material covering the back of your throat (can block your airway, causing you to struggle for breath) Complications: Myocarditis, Laryngeal palsy, "dysphagia" Dx: made clinically and confirmed by culture Prevention: Vaccinate ->childhood immunization with booster Tx:• Antitoxin (from horses), PCN or macrolide

Fluoroquinolones Drug Reactions

Divalent and trivalent cations - ALL FQs ->Zinc, Iron, Calcium, Aluminum, Magnesium -Impair oral absorption of orally-administered FQs - may lead to CLINICAL FAILURE -Administer doses 2 to 4 hours apart QTc prolonging agents ->Antipsychotics, azoles, etc

Cephalosporins

Divided into 4 (or 5) major groups referred to as "Generations" "Generations" generally based on: antimicrobial activity-> 3rd and 4th gens=broadest spectrum, associated with C. Diff #2 on list. Do not cover Enterococcus spp (exception ceftaroline)

Tetracyclines

Doxycycline (Vibramycin®) (iv,po), minocycline (Minocin) (iv,po) MOA: inhibits protein synthesis (30s ribosomal subunit) Spectrum of activity: broad ->Gram-positive, gram-negative, atypicals, Borrelia, Rickettsia, Chlamydia, Treponema ->Covers MRSA Adverse events: N/V, photosensitivity, tooth discoloration in children < 8, esophagitis Drug interactions: Divalent and trivalent cations **First-line therapy for most tick-born diseases Indications: tick-born diseases, community-acquired pneumonia, skin and soft tissue infections, syphilis, chlamydia

Group D Strep

Enterococci->Diplococci: occur in pairs. Gram Positive 2 species are common commensal organisms of our intestines. ->E. Faecalis (MAJORITY) ->E. Faecium These are gamma hemolytic, facultative anaerobes that tolerate a wide range of environmental conditions (AKA very hardy bugs). Usually cause: UTIs, bacteremia, diverticulitis, bacterial endocarditis.

Levofloxacin (Levaquin®)

Fluoroquinolone Spectrum of activity: broad ->Gram-negative = gram positive ->Covers Pseudomonas ->Good Strep pneumoniae activity + Atypical...NO anaerobes. Indications: UTIs, community-acquired pneumonia

Ciprofloxacin (Cipro®)

Fluoroquinolone Spectrum of activity: broad ->Gram-negative-> atypical bact->Best activity vs Pseudomonas aeruginosa, no anaerobes/GP. Indications: UTIs (if tried other agents and failed), nosocomial pneumonia

Moxifloxacin (Avelox®)

Fluoroquinolone Spectrum of activity: broad->Similar to levofloxacin with the following exceptions: No Pseudomonas activity, Covers anaerobes Fun fact: does not concentrate in the urine Indications: pneumonia, intra-abdominal infections

Clostridium Tetani

Found in soil and gains entry through a deep puncture (nail) Toxin interferes with the inhibitory system (Renshaw Cells) causing muscle spasms Incubates for about 8-12 days. S&S: Lock jaw (trismus) muscle spasms, increased reflexes, respiratory failure (diaphragm ceases up) PREVENT W VAX!!!! Booster every 10 years Tx: Human tetanus IGM, PCN to eradicate any bacteria , Benzodiazepines to treat muscle spasms

Metronidazole (Flagyl)

IV or PO MOA: Inhibits DNA synthesis Spectrum of activity: narrow - >Anaerobes Adverse events: disulfiram-like reaction when taken with alcohol, peripheral neuropathy with long term use, N/V/D First found to be active against protozoa Indications: anaerobic infections, Trichomonas and other protozoal infections, BV

Trimethoprim/Sulfamethoxazole (Septra, Bactrim)

IV or PO MOA: Inhibits folic acid synthesis Spectrum of activity: broad ->Some Gram-positive, Gram-negative, protozoa, Pneumocystis jirovecii, Covers MRSA Adverse events: Stevens Johnson syndrome/Toxic epidermal necrolysis, nephrotoxicity, phototoxicity, hyperkalemia, bone marrow suppression ->Do not prescribe to patient with a sulfa allergy First line therapy for MRSA skin and soft tissue infections; dosed on trimethoprim component Indications: SSTIs, UTIs, Pneumocystis pneumonia

Clindamycin (Cleocin)

IV or PO MOA: Inhibits protein synthesis (50s ribosomal subunit) Spectrum of activity: broad -> Gram-positives and anaerobes->Some activity against MRSA Adverse events: GI & C. difficile Indications: skin and soft tissue infections and anaerobic infections

Vancomycin

IV or PO Spectrum of activity: Gram-positive aerobes and anaerobes Drug of choice for invasive MRSA infections Adverse events: NEPHROTOXICITY & vancomycin infusion reaction (slow down infusion, can still use it) Requires therapeutic drug monitoring - Troughs: 10-20 mcg/ml OR AUC/MIC 400-600 • Indications: MRSA infections (IV only), C. diff infections (oral only)

Carbapenems

Imipenem/cilastatin (Primaxin®), Meropenem (Merram), Ertapenem (Invanz®), Doripenem (Doribax)- (all iv/inpt-usu restricted bc very broad spectrum) Spectrum of activity: very broad! ->Covers Gram-positive, Gram-negative, and anaerobes ->All cover Pseudomonas EXCEPT FOR ertapenem Imipenem and meropenem have formulations with beta-lactamase inhibitors: reserved for MDR infections...DO NOT COVER MRSA Cilastatin (Not a BLI) prevents the breakdown of imipenem by renal dihydropeptidases thereby increasing renal recovery and prevention of a toxic metabolite->Serious AE - seizures (>imipenem) Indications: nosocomial infections, intra-abdominal infections High association with C. difficile infection # 1 on list

Abx dosing depends on

Indication, Renal Function, Hepatic Function/ Renal bc most drugs are renally cleared Hepatic bc most drugs are filtered by the liver and some are hepatotoxic.

Secondary Syphilis

Itchy rash on palms and soles. This rash may start on the trunk and spread outward. Transmitted directly or sexual contact. Dx: VDRL/RPR- non-trepemonal->trepemonal tests Tx: Single IM injection of Benzathine Penicillin G ->Even in Penicillin-allergic patients (you can adjust administration) Can use Doxy... dosage depends on stage of disease. Note: Jarisch-Herxheimer reaction may occur: Acute febrile reactions accompanied by headache and myalgias within 24 hr after treatment->Release of endotoxin-like substances when large numbers of Treponema pallidum are killed by antibiotics causing a Cytokine storm!

Tertiary Syphilis

Late (tertiary) syphilis includes gummatous (soft, non-cancerous) lesions involving: • Skin • Bones • Viscera • cardiovascular disease • Nervous system and ophthalmic lesions Argyll Robertson pupil (they "accommodate, but do not constrict to light) Tabes dorsalis crises (severe pain and neurological decompensation) All cases of syphilis must be reported to the appropriate public health agency for contact tracing Careful follow-up is essential to monitor the effectiveness of treatment and to identify treatment failures HIV testing and screening as well as treatment of concurrent sexually transmitted diseases should be done

Toxic Shock Syndrome Toxin (TSST-1)

Life threatening condition!!! Super T cell antigens (toxin) are the issue here which is produced by some S. Aureus isolates. TSST-1 binds class II MHC, induces expansion of T lymphocytes, release of large amounts of IL-1, IL-2 and TNF (CYTOKINE STORM) THINK TAMPONS!!! also medical packing S&S: Rash, N/V, myalgia, hypotension, can lead to multi-system organ failure->death w/in 48 hrs. Dx: Clinical based on symptoms, cultures could show up neg. Tx: remove source of toxin & supportive care (hydration/abx)

Minimum Inhibitory Concentration (MIC)

Lowest concentration of antibiotic that inhibits visible bacterial growth after 24 hrs

Beta Lactams

MOA: inhibits cell wall synthesis Classes: PCN, Carbapenems, Cephalosporins, and Monobactam AE: NVD, rash, possible anaphylaxis w allergies

Mycobacterium Avium Complex (MAC)

Most common bacterial infection in HIV/AIDs Found in water and soil x-ray-> indistinguishable from TB Tx: Abx

PPD Skin Test Guidelines

Most common method currently used that demonstrates infection with M. tuberculosis in the absence of active TB. >/= 5 mm is positive in the highest risk group: HIV +, recent contact with TB + pt, nodular or fibrotic changes in CXR, organ transplant >/= 10 mm is positive if: recent arrival (<5 yrs) from a high prevalence country, IV drug users, resident/employee in high risk congregate settings, mycobacteriology lab personnel, comorbid conditions, children <4 years old, infants/children/adolescents exposed to high risk categories. >/= 15 mm in people with no known RFs for TB.

Penicillinase-resistant / "Antistaphylococcal Penicillins"

Nafcillin (iv), Dicloxicillin (po) Spectrum of activity: strep and MSSA Nafcillin is drug of choice for severe MSSA infections (ex. Bacteremia, Endocarditis) Indications: skin and soft tissue infections, severe MSSA infections

Characteristics of Gram Positive Bacteria

PURPLE STAIN! Very thick peptidoglycan (protein) cell wall NO outer membrane

Staph Epidermidis

Part of the normal skin flora->gram positive grape like clusters on skin Has a biofilm that sticks on hardware/devices! Affects immunocompromised and is normally hospital acquired. Can cause endocarditis Dx: Blood culture, s&s of infx. Tx: Remove the device!!! Abx (IV 4-6 weeks)

Natural Penicillins

Penicillin G (iv-inpt), Penicillin VK (po-outpt), penicillin G benzathine (im) Spectrum of activity: very narrow! Fun facts: NO Staphylococcal Activity Indications: Strep throat (oral), syphillis (IM/IV), penicillin susceptible strep infections when susceptibilities are known

Yersinia Pestis

Plague or "Black Death" Gram-negative, Rod, Nonmotile, Coccobacillus, Facultative anaerobe Three main forms: 1. Pneumonic (Pulmonary), 2. Septicemic (Blood), 3. Bubonic plagues (Lymph node) Transmission: Rodents.....flea bites (1-7 days), Infected human (Airborne) (2-4 days) S&S: Fever, malaise, sore throat, myalgias, Lymphadenopathy inguinal area, Bubonic lesion at site of entry Dx: Blood cultures Tx: Abx Prevention: • VACCINATE!!! If Traveling or military

Staph Bacteremia

Presence of viable bacteria (S. Aureus) circulating in the blood. Et/Comp: Endocarditis (vegetation on valves bc heart has poor immune syst), Osteomyelitis, Implantable device, Metastatic deep infx. Dx: Blood Culture Tx: -> If Skin is source: 10-14 days abx -> anything else: 4-6 weeks IV abx & remove hardware when pt stable.

Clostridium Perfringes

Present in soil and raw meat Most common cause of FOOD POISONING! S&S: Abd pain, diarrhea (starts w/in 6-24 hours and lasts about 24 hours=QUICK bc food is in intestines in 4 hours), usually no vomiting or fever. Tx: Fluids, rest, education (food safety-maintain temp of 140).

Primary Syphilis

Presents with a single painless chancre on the genitals with a "punch out" appearance which gets better in 3-6 weeks. Transmitted through direct contact or sexual intercourse and has a 3 week-3 month incubation period. Regional lymphadenopathy (rubbery, discrete, nontender) Dx: Darkfield microscopy. Tx: Single IM injection of Benzathine Penicillin G ->Even in Penicillin-allergic patients (you can adjust administration) Can use Doxy... dosage depends on stage of disease.

Rifamycins

Rifampin (iv,po) MOA: inhibits RNA synthesis Spectrum of activity: narrow ->Mycobacterium tuberculosis, some Gram-positives Adverse events: hepatotoxicity, discoloration of bodily fluids (red/orange), N/V Drug interactions: MANY!!!!!!! - CYP enzyme inducer Not often used as monotherapy Indications: tuberculosis, endocarditis, prosthetic infections

RIPE Side Effects

Rifampin: Red urine discoloration Isoniazid: drug induced lupus, B6 deficiency, neuropathy Pyrazinamide: GI sx (puke), hyperuremia, gout. Ethambutol: Optic Neurites

Staph Aureus Osteomyelitis

S. Aureus is the most common cause of osteomyelitis (bone infx). Hematogenous: Infx that seed the bone in the setting of bacteremia (blood) Non-Hematogenous: Direct inoculation (bone fracture/joint replacement) spreads from surrounding tissue. S&S: Pain, Localized Tenderness, Warmth/Erythema, Fever, Malaise, Diaphoresis, Bone Pain (important with DM II bc they can't feel the pain as well so infx spreads longer before they know something is wrong and seek tx). Dx: Wound and Blood Cultures, CBC (leukocytosis), ESR (faster=infx), Glucose, Bone biopsy (last), imaging (x-ray [moth eaten-"hollow bone"] MRI, CT) Tx: 4-6 weeks of abx determined by C&S.

Streptococcus Pharyngitis

S. Pyogenes Gram positive. Group A Beta Hemolytic is the MOST COMMON cause of pharyngitis. S&S: fever, tender anterior adenopathy, lack of cough, tonsillar exudate, strawberry tongue, scarlet fever (rash caused by strep toxin), absence of rhinorrhea. Transmission: Droplets or directly, or touching something that has the droplets on it and touching your nose, eyes, mouth. Dx: Rapid strep test (less invasive=initial test) and culture (the definitive), increased WBC count (Neutrophils) Complications: Otitis Media, Sinusitis, Abscess Glomerulonephritis, rheumatic heart disease (strep epitope has proteins that mimic our heart valves/kidney tissues, causes body to attack our own tissues) Tx: Abx (PCN, Augmentin, Amoxicillin-kids)

Eikenella Corrodens

"Fight Bite" Gram Negative, coccobacilli, Anaerobic Commensal of the human mouth & upper respiratory tract Infection does NOT become clinically evident until a week or more after the injury Needle-licker's osteomyelitis: lick off needle to "clean" it, then inject and can hit the bone. Tx: Abx

Erysipelothrix rhusiopathiae

"Fishmonger's Hand" Gram-positive, Rod-shaped Does NOT produce spores E. rhusiopathiae is primarily considered an animal pathogen Bacterium can also cause zoonotic infections in humans, called erysipeloid Individuals who handle fish and raw meat S&S: Mild cutaneous cellulitis form known as erysipeloid (fish poisoning), Sepsis/bacteremia causing (rare), but can be a culprit of endocarditis Tx: Abx

Salmonellosis

"Salmonella" Gram Negative, rod, Nonspore-forming, Motile, Peritrichous flagella "All around the cell body," Facultative aerobes Two species of Salmonella: ->1. Salmonella bongori: Cold-blooded animals "reptiles" ->2. Salmonella enterica: Warm blooded animals, "Several subspecies" & Environment Salmonellosis: Symptomatic infection caused by bacteria of the Salmonella type ->Salmonellosis is one of the most common causes of diarrhea globally ->Typically occurs between 12 - 36 hours after exposure with symptoms lasting from two to seven days Spread by eating contaminated meat, eggs, or milk S&S: Diarrhea, Fever, Abdominal cramps , Vomiting, Dehydration Disease caused by Salmonella serotype Typhi bacteria: ->Enteric fever or Typhoid fever: Transmitted through contaminated food or drink (dairy or poultry) - Infects intestines-> lymphatics->rest of organs - Incubation 5-14 days Signs and ->Symptoms: - Malaise - Sore throat - Low grade fever - Diarrhea (pea soup) Dx: Culture?- Early stages Tx: Quinolone (Cipro)

Shigella

"Shigellosis" Gram negative, Rod, Facultative aerobe Shigella causes disease only in primates Transmitted by fingers, flies, food and feces (Fecal-oral) Incubation 1-4 days S&S: Bloody, mucoid diarrhea, High fever, abdominal cramps Dx: • Stool Culture Tx: Mild cases: Supportive (rehydration, rest) Severe cases: Abx-> Quinolone (Cipro)

Bordetella Pertussis

"Whooping Cough" bc of loss of mucus production gram negative, Coccobacilius, Aerobic, NOT motile Transmission: Airborne droplets, Direct contact with infectious discharge Incubation 7-17 days Most common in children less then 2 years old Phases: Catarrhal, Paroxysmal, Convalescent Dx: • Nasal culture, Takes 7-10 days to grow Prevention: VACCINATE all infants and mothers, caretakers Tx: Abx (macrolides)

Goals of Antibiotic Therapy

1. Cure the infection 2. Limit hard (adverse effects/secondary infections) 3. Limit resistance (bacteria have many methods to overcome drugs-the more we use it the smarter the bacteria become)

Factors to consider when selecting an Abx

1. Spectrum of activity 2. Patterns of resistance (utilize antibiogram if available) 3. Evidence or track record for the specified infection 4. Achievable serum, tissue, or body fluid concentration (e.g. cerebrospinal fluid, urine) 5. Comorbid conditions (eg renal/hepatic dfx, pregnancy) 6. Allergy 7. Toxicity 8. Drug-drug interactions 9. Formulation (IV vs. PO) 10. Adherence/convenience (e.g. 2x/day vs 6x/day) 11. Cost

Aminopenicillins

Ampicillin (iv,po), Amoxicillin (po) Spectrum of activity: narrow Ampicillin is drug of choice for enterococcal infections (when susceptible) and Listeria infections Indications: Ampicillin->meningitis, severe enterococcal infections (when susceptible) Amoxicillin -> bacterial rhinosinusitis, strep throat Aminopenicillins+: Ampicillin + Sulbactam (Unasyn®) (iv), Amox + Clavulanic acid (Augmentin®) (po) Sulbactam & clavulanic acid are beta-lactamase inhibitors: Increase Gram-positive activity, including beta lactamase (+) Staph. aureus, increased Gram-negative & anaerobe activity Causes diarrhea Spectrum of activity: broad Amoxicillin + clavulanic acid (Augmentin) is drug of choice for animal bites Indications: animal bites, bacterial rhinosinusitis Extended Spectrum Aminopenicillins: Ticarcillin + Clavulanic acid (Timentin®)(iv) & Piperacillin + Tazobactam (Zosyn®)(iv) Tazobactam & clavulanic acid are betalactamase inhibitors Spectrum of activity: very broad (including Pseudomonas) Gram-positive, Gram-negative, anaerobes Indications: empiric nosocomial infections (hospital infections), intra -abdominal infections

Bacillus Anthracis

Anthrax Gram positive Rod , Aerobic, Spore forming Spores are in soil on animal product hides, bristle and wool of infected animals 3 types 1: Cutaneous anthrax: Occurs 2 weeks after exposure to spores. Large, painless ulcer with black eschar and surrounding edema 2: Inhalation anthrax: Lung infection, resulting sepsis 3: Gastrointestinal anthrax: Exposure to meat products with spores. N/V/D and fever. Dx: History-> Travel to Middle East, Africa, South America or Asia, Exposure to wool, hides or animal hair from endemic areas Bioterrorism Gram Stain and culture reveals bacteria CXR - Widened mediastinum - Hemorrhagic lymphadenitis Tx: Abx

Pulmonary Mycobacterium Tuberculosis

Atypical Bacteria Infectious, inflammatory systemic disease affecting the apex of the lungs (more O2, less perfusion, less chance of immune response), May disseminate to involve lymph nodes and other organs Caused by tubercle bacillis which can survive in sputum for months. S&S: Often sx are delayed for a year after exposure...Primarily attacks the lungs but can attack kidney, brain and spine, Prolonged cough for 3 weeks, chest pain, bloody sputum, Weakness, chills, night sweats, weight loss, fever, Granulomas (T cell wall), Caseous Necrosis (Liquified, cheese like), and subsequent cavity formation. Transmission: Air droplets, not by shaking hands. Dx: Acid-fast stains such as Ziehl-Neelsen, Fluorescent stains such as auramine, H&P, Tuberculin skin test, Chest radiograph, Microscopic examination, Culture of sputum (definitive) Stages: 1. Primary: usually asx 2. Secondary: the most clinical stage. reactivated infection, can move to joints. 3. Tertiary: Prevention: covering mouth!!!! Vax, but not in the US. ***when it becomes encapsulated in the body, it can lie dormant for years. Tx: RIPE (Rifampin, Isoniazid, Pyrazinamide, Ethambutol)

Macrolides

Azithromycin (iv,po) and clarithromycin (Biaxin) (po) MOA: Inhibits protein synthesis (50s ribosomal subunit) Spectrum of activity: broad->Gram-positive and Gram-negative->Covers atypical pathogens->No anaerobic activity Adverse events: QTc prolongation, N/V Azithro often preferred over clarithro due to < DDIs and better tolerability Indications: community-acquired pneumonia, strep throat, mycobacterium avium complex, chlamydia Fidaxomicin (Dificid) (po-Very expensive) Adverse events: nausea, vomiting, abdominal pain - Indications: preferred therapy for C. difficile infection according to guidelines, however cost is prohibitive

Monobactams

Aztreonam (Azactam®) (iv) **Expensive! Spectrum: only gram negative aerobes, Covers Pseudomonas No cross reactivity with penicillins/cephalosporins/carbapenems Indications: nosocomial infections/alternative agent to when patient has a severe PCN reaction

Fluoroquinolones

Ciprofloxacin (Cipro), levofloxacin (Levaquin), moxifloxicin (Avelox) - all available IV and PO MOA: Inhibit bacterial topoisomerases which are necessary for DNA synthesis ->DNA gyrase - Primary target in gram-negative ->Topoisomerase IV - Primary target for many gram-positive bacteria Spectrum of activity - varies with agent All have atypical coverage

Bacteriostatic

Clindamycin, macrolides, doxycycline, linezolid Inhibits the bacteria

Spirochetes General Characteristics

Flexible spirally twisted bacterium • Spirochetes are the cause of syphilis and Lyme disease Generally regarded as Gram negative bacteria, because they have a thin peptidoglycan layer BUT Gram staining is NOT commonly used to stain them as they do not take up the stain well Silver stains are typically used to identify spirochetes

Clostridium Septicum

Gas Gangrene (RARE) Myonecrosis (due to release of endotoxin) Spread from the gastrointestinal tract Associated with colorectal cancer and other defects of the bowel Mortality rate of approximately 79% Tx: Abx, Surgical Debridement (have to open up to get gas out and clean up tissue), Hyperbaric Oxygen Therapy (HBOT-compression of air in affected tissues transiently reduce tissue pressure and improve perfusion, O2-dependent bacterial killing by host neutrophils is enhanced in hyperbaric conditions)

Fluoroquinolones Adverse Effects

Gastrointestinal (Nausea, vomiting, diarrhea, dyspepsia) Central Nervous System (Headache, agitation, insomnia, dizziness, rarely, hallucinations and seizures (elderly)) Peripheral neuropathy BBW: Tendonitis/tendon rupture w prolonged use Hepatotoxicity Phototoxicity Cardiac (Variable prolongation in QTc interval, >500, avoid Fluoroquins) C. difficile infection (3rd on list) Recent warning to avoid in patients with history of aortic aneurysms Dysglycemias Delirium

Renal Dose Adjustments

Glomerular filtration rate (GFR) - single best indicator for kidney function Serum creatinine used to estimate GFR Numerous equations to estimate Creatinine Clearance (CrCl) ->Cockcroft-Gault - FDA approved drug dosing recommendations are often based on this equation - CrCl =[(140-age)*wt (kg)] / (SCr (mg/dL)* 72) ->Multiply answer by 0.85 for females

Streptococcus Infections

Gram Positive bacteria arranged in pairs or chains (can appear bent or twisted) Most are facultative anaerobes (where they can grow both aerobically and anaerobically) Classified based on their hemolytic properties (on blood agar plates): -Alpha: oxidization of iron in hemoglobin molecules within RBCs, leaves a greenish color on agar plate. -Beta: complete rupture of RBCs, wide clear areas on agar plate. -Gamma: No hemolysis

Staphylococcus Aureus

Gram Positive in grape like clusters. ~25% of patients are asymptomatic carriers-they carry it on their skin. When there is a breach in the skin barrier (cuts) is when it causes infection OR with immunosuppression. Depending on where it colonizes is where the infection will occur. Common Diseases: Impetigo, Abscesses, etc. Dx: Wound and Blood CULTURE!!! Tx: I&D, Wound Care, Abx ->MSSA: PCN, Keflex (1st gen cephalosporin) ->MRSA: Bactrim, Doxy, Clinda, Vanc (inpt)

Vibrio Cholera

Gram negative, (Curved Rod "Looks like a Comma"), Facultative anaerobe, Flagellum Bacterium's natural habitat is brackish or saltwater Incubation 11-72 hours Humans only affected Transmission via food and water->Areas of poor sanitation-Central America, Africa Secretes an enterotoxin -> illness S&S: Profuse rice-watery diarrhea, Severe dehydration Dx: Culture: Stool Tx: Supportive care (rehydration), Abx

Neisseria Gonorrhoeae

Gram negative, Diplococci Transmission: STI and Perinatal Men S&S: Dysuria and milky discharge, Epididymitis, prostatis Women S&S: Dysuria and milky discharge, Cervicitis, PID-can be asx. Both: Urethritis, Pharyngitis, Conjunctivitis When it goes untreated: BAD!...can become disseminated->Purulent arthritis (Triad: 1. Rash 2. Synovitis 3. Arthralgias) Conjunctivitis: Babies through the birth canal Dx: Cultures (men and women-> urine, women->cervix) Prevention: condoms, abstinence, know partner, frequent testing. Tx: Abx->Ceftriaxone and Doxy (doxy=chlamydia)

Chlamydia Trachomatis

Gram negative, Ovoid shape, Nonmotile Transmission: STI and Perinatal S&S: Lesions on genitalia (Cervicitis or Urethritis), Lymph Nodes 1-4 wks Dx: Cultures: same as gonorrhea -> Culture-> Nucleic Acid Amplification Testing=best initial test for gonn or chlam. Prevention: same as gonorrhea. Tx: same as gonorrhea

Brucellosis

Gram negative, Rod, w/out a capsule, Nonmotile Highly contagious zoonosis caused by Ingestion of unpasteurized milk/undercooked meat of infected animals OR Close contact with their secretions Incubation: 1-3 weeks S&S: Cyclic fever (high/low), Enlarged lymph nodes (spleen), Muscle pain/sweats Dx: Culture: Blood-> Brucella titer (PCR) Tx: Abx

Clostridium Species

Gram positive bacilli (rod shaped) Obligate anaerobes (grows in the absence of O2) Produces Endospores which enable the bacteria to lie dormant for extended periods of time Alpha Toxin Lecithinase: Phospholipase...destroys cell membranes of RBC, WBC, muscles Inhabits soil and intestinal tract and the lower reproductive tract in women.

Staph Saprophyticus

Gram positive grape like clusters but in urinary tract. 2nd MC cause of UTIs! "Honeymoon Cystitis" bc happens ~24 hrs after sex. S&S: Burning sensation with urination (bc nerves are sensitive from inflammation), Urge to urinate more often, Dripping effect after urination, Razor like pains during sex. Tx: Abx.

Listeria Monocytogenes

Gram positive, Rod, Facultative anaerobe Grows intracellular in host Does NOT produce endospores Listeriosis can cause serious illness especially in Pregnant women (toxic to fetus), Newborns, Immunocompromised (transplant pts), Elderly May cause gastroenteritis in others who have been severely infected Transmission via contact with: Animal Feces, Unpasteurized Dairy (deli meats and soft cheeses), Contaminated Vegetables ->Listeria bacteria can survive refrigeration and even freezing Tx: Abx

Pasteurella Multocida

Gram-negative, Non-motile coccobacillus Cause a zoonotic infection in humans as a result of bites/scratches/licks from domestic pets Many mammals (domestic cats, dogs & birds) harbor it as normal respiratory microbiota Most prevalent bacteria present in domestic and wild animals worldwide Aggressive: skin manifestations typically appear ~ 24 hrs following bite Fairly sensitive organisms Tx: PCN-based regimen (Augmentin)

Escherichia coli

Gram-negative, Rod-shaped, Facultative aerobe Found in the lower intestine: benefit hosts by producing vitamin K2 Most strains are harmless but some strains cause: Food poisoning, Pneumonia, UTIs (MOST COMMON CAUSE) E. coli makes you sick by making a toxin called Shiga which damages the lining of your intestine Comes from: Under cooked meat, Unpasteurized milk, Petting Zoo's (Fairs), Improper Fecal Oral Hygiene Escherichia coli O157:H7 strain (the bad one) "Typically foodborne illness" ->Transmission is via the fecal-oral route ->Shiga toxin-producing types ->S&S: abdominal cramps, vomiting, and bloody diarrhea ->Leading cause of acute kidney failure in children (Hemolytic Uremic Syndrome)->same S&S above + seizures/fever Tx:

Spectrum of Antibiotics

Gram-positive vs. Gram-negative Anaerobes (generally in mouth and gut) Atypicals MDR pathogens Pseudomonas MRSA Broad: Inhibit/kill many different species of bacteria Narrow spectrum: Inhibit/kill only a few species of bacteria->This is after you have a definitive pathogen.

What are HACEK Organisms

Group of gram-negative bacteria that cause culture-negative endocarditis: (initial culture is negative bc need a special plate and takes a long time to come back) 1. Haemophilus 2. Actinobacillus 3. Cardiobacterium 4. Eikenella 5. Kingella

Haemophilus Influenzae

H. Flu (BACTERIAL) Gram-negative, Capsulated, Coccobacillary, Facultative anaerobe Presence of the capsule in encapsulated type b (Hib) known to be a major factor in virulence->Allows resistance to phagocytosis and complement-mediated lysis Entry through upper respiratory tract Causes: Sinusitis, Epiglottitis, Otitis media, Pneumonia, Meningitis Epiglottitis: Abrupt onset of fever, Inability to control oral secretions (hot potato voice)->AIRWAY OBSTRUCTION->MEDICAL EMERGENCY Dx: Direct Laryngoscopy, X-ray (thumb print sign) Tx: Abx, Supportive care, Intubation (especially children) Meningitis: Stiff neck=Dx. Abx=Tx. VACCINATE!!!!

Empiric Therapy

Infection not well defined ("best guess" ) Broad spectrum Multiple drugs More adverse reactions More expensive ***Use antibiograms to help guide empiric therapy...ensure to look at other factors as well such as allergies, comorbidities, etc.

Directed Therapy

Infection well defined (e.g. culture and susceptibilities returned) Narrow spectrum One, seldom two drugs Less adverse reactions Less expensive

What is Infective Endocarditis

Invasion of the heart valve or endocardium leading to colonization and eventual destruction of the cardiac tissue-> Gram negative issue generally. Risk factors: IV drug use (staph aureus), Structural heart abnormalities (prosthetic heart valve) S&S: Low grade temperature (most common 90%) • Malaise, New cardiac murmur, Heart failure, EKG changes with conduction abnormalities, Splinter hemorrhages, Osler nodes (painful), Janeway lesions( painless on hands and feet), Roth spots "hemorrhage from retinal blood vessel Common Causative Agents: Staph Aureus, Community Acquired Enterococcus, HACEK Organisms.

How to Diagnose Infective Endocarditis

Major Criteria 1: 2 blood cultures 2: Echocardiogram w endothelial involvement (vegetation, abscess, prosthetic valve) (Transthoracic: Ultrasound Guided, Transesophageal-tube in eso) 3: New Murmur Minor Criteria 1: Predisposing Heart Condition 2: IV drug use 3: Fever >100.4 4: Immunological phenomena: (Glomerulonephritis, Osler nodes, Roth spots, Rheumatoid factor) 5: + culture or echo not meeting criteria 6: vascular issues. NEED: 2 major, 1 major w 3 minor, or 5 minor

Neisseria Meningitidis

Meningococcal Meningitis Gram negative, Diplococci (meningococcus) Cause Meningitis and other forms of meningococcal disease Only form of bacterial meningitis known to occur epidemically Meningococcemia "Life-threatening sepsis" ~ 10% of adults are carriers of the bacteria in their nasopharynx and it is an exclusively human pathogen Main cause of bacterial meningitis in children and young adults and causes developmental impairment and death in ~ 10% of cases N. meningitidis spread through saliva and respiratory secretions Pathogenesis: Infects host cells by sticking to them with long thin extensions called pili and surface-exposed proteins Opa and Opc 13 identified capsular types of N. meningitidis Six (A, B, C, W135, X, and Y) account for most disease cases worldwide RF: Children under 5, Young adult (think college age), Immune deficiency S&S: High fever, Headache, Purpuric Rash (non-blanching), Confusion Dx: Lumbar puncture, Gram Stain, Culture on Chocolate agar plates Tx: Antibiotics PREVENTION ....VACCINATE & Breast Feeding for 6 months

Aminoglycosides

Not used frequently Gentamicin, tobramycin, amikacin (all iv) MOA: inhibits protein synthesis (30s ribosomal subunit) Spectrum of activity: broad=>Mainly Gram-negative agents - all cover Pseudomonas ->Synergy for Gram-positive infections Adverse events: NEPHROTOXICITY & OTOTOXICITY Requires therapeutic drug monitoring due to above. Indications: nosocomial infections, UTIs, endocarditis

Characteristics of Gram Negative Bacteria

PINK STAIN! Very thin peptidoglycan (protein) inner membrane WITH an outer membrane.

Nitrofurantoin (Macrobid)

PO MOA: inhibits everything Spectrum of activity: narrow->Limited Gram-positive and Gram-negative->mostly for urinary issues. Adverse events: pulmonary toxicity, hepatotoxicity, discoloration of urine (brown) Not effective in patients with poor renal function (CrCl < 30 ml/min) Indications: UTIs (not pyelonephritis)

Fosfomycin (Monurol)

PO, Expensive MOA: inhibits cell wall synthesis Spectrum of activity: narrow->Limited Gram-positive and Gram-negative Adverse events: well tolerated Given as a single dose for uncomplicated cystitis Indications: UTIs

Clostridium Botulinum

Spores in soil-> Contaminate vegetables and meats **No honey in infants or canned foods. Canned or vacuumed spores survive bc they germinate in anaerobic environment, resistant to degradation by enzymes found in the gastrointestinal tract, allows ingested toxin to be absorbed from the intestines into the bloodstream Released neurotoxin inhibits acetylcholine release parasympathetic ganglia, neuromuscular junction (causes symmetric paralysis within 12-72 hours after exposure->Most potent toxin known to humankind) Has been used now as Botox/Medically......... it does not ware off->the nerve will sprout new endings. S&S: Descending flaccid paralysis, Diplopia, Dysphonia, Dysphagia, Dysarthria, Ptosis, Floppy baby (descending parallel fashion), Constipation (need NMJ for peristalsis) Tx: A trivalent (types A,B,C) equine serum toxin, Supportive care with mechanical ventilation, Debridement of wound

Pneumococcal Pneumoniae

Strep Pneumoniae Alpha hemolytic, diplococci "Lancet shaped" IgA Protease->destroys IgA->MUCOSA! Resides asymptomatically in healthy individuals in the oropharynx, but CAN become pathogenic. Spreads directly through person to person contact in IMMUNOSUPPRESSED!!! Can also be caused by autoinoculation if a person aspirates or has a PE or splenectomy (bc it is an encapsulated bacteria) Presentation: Most common type of community-acquired pneumonia. ->can cause sepsis in pts with splenectomy. ->Rusty sputum, productive cough, fever, pleuritic pain Prevention: 2 types of vaccine for this 1: Pneumococcal conjugate vaccines (13, 15, or 20 strains covered). This has better immunogenicity (bc of the protein conjugate) but narrower spectrum of pneumococcal serotypes 2: Pneumococcal Polysaccharide vaccine (23 strands covered, but need a good B cell response bc T cells will not pick this up) Complications: MOPS: Meningitis, Otitis Media, Pneumonia, Sinusitis. Dx: Chest X-Ray (lobular infiltrate/consolidation), Sputum/blood culture! Tx: PCN, cephalosporin (2nd or 3rd gen), macrolide, fluoroquinolones