Microbes 1. Overview of Bacteriology a. Characteristics of bacteria i. Single cell ii. No nuclear membrane iii. Single circular DNA iv.

No organelles v. 70s ribosomal DNA (different from human) vi. No membrane sterols vii. Peptidoglycan cell wall (not present in Euks) viii. Reproduction by binary fission ix. Susceptible to antibiotics b. Gram Positive: i. Stain blue ii. Have thick outer peptidoglycan cell wall c. Gram Negative i. Stain pink ii. Have LPS (endotoxin) on outside iii. Thinner layer of peptidoglycans, sandwiched between iv. Porins on outer membrane layer d. Gram Positive Cocci i. Staph 1. Grows in clusters 2. Catalase positive 3. Facultative Anaerobes 4. Coag POSITIVE staph = S.Aureus 5. Coag NEGATIVE staph- routinely found on skin. Usually not harmful 6. Staph Aureus a. Skin and soft tissue infections (Abscess) b. Pneumonia c. Bone and joint infections d. Bacteremia e. Endocarditis f. Catheter infections g. Toxin syndromes i. TSST ii. Scalded skin iii. Food poisoning (enterotoxin) h. MRSA i. Hospital Aquired ii. Community acquired

1. Increasingly prevalent 2. Includes Panton-Valentine Leukocidin ii. Strep 1. 2. 3. 4. 5. Grows in chains Catalase Negative Facultative Anaerobes Ferment carbohydrates producing Lactic Acid Types of Strep a. Group A Strep (Pyogenes) i. Beta Hemolytic ii. Bacitracin sensitive iii. Has a capsule of hyaluronic acid iv. Usu asx colonization of respiratory tract v. Person-to-person spread vi. Diseases 1. Most are suppurative 2. Pharyngitis 3. Scarlet Fever 4. Skin Infections 5. Bacteremia 6. TSST 7. Rheumatic fever a. 10 days after GAS b. Migratory polyarthritis, carditis, subQ nodules, erythema marginosum, chorea (Major Jones Criteria) 8. Glomerulonephritis b. Group B strep (agalactiae) i. Narrow zone of beta hemolysis ii. GI/GU iii. Babies get it from colonized mothers iv. Now, if positive, put on antibiotics before giving birth c. Strep Pneumoniae i. Alpha hemolytic ii. Lancet shaped iii. Optochin sensitive (viridians is not) iv. Soluble in bile (other streps are not) v. Have a polysachharide capsule (Candy coating) 1. Capsule is basis for vaccine vi. Diseases 1. Pneumonia a. #1 for community acquired pneumonia

2. 3. 4. 5.

Otitis, sinusitis Meningitis (ties for #1) Bacteremia Skin and joint infections

iii. Enterococci 1. E. Faecalis, E.Faecium 2. Grows in chains/pairs 3. Catalse Negative 4. Usu non-hemolytic 5. Grows in 6.5% NaCl 6. Diseases a. Endocarditis b. UTI c. Nosocomial (Wounds, catheters) e. Gram Negative Bacilli i. MacConkey Agar 1. Grows Gram neg a. Lactose fermenters grow PINK b. Non-lactose fermenters grow COLORLESS c. Lactose test helps ID the bacteria ii. Enterobacteriaciae 1. Salmonella, shiglella, e.coli, klebsiella, yersinia, enterobacter 2. Often common in the ENVIRONMENT 3. Oxidase negative 4. Ferment glucose 5. Diseases a. Gastroenteritis b. UTI c. Bloodstream infection d. pneumonia e. plague iii. P. aeruginosa 1. Obligate aerobe 2. Does NOT ferment lactose 3. Does NOT ferment glucose 4. Oxidase positive 5. Sweet odor 6. Produces a green color iv. HACEK group 1. H. Influenza f. Gram Negative Cocci i. Neisseria

Grow in pairs Prefer high CO2 Oxidase positive Species a. Meningitides i. Carbohydrate capsule b. Gonorrheae i. Also encapsulated ii. Uses only GLUCOSE ii. Moraxella 1. Otitis, sinusitis, bronchitis g. Gram Positive Bacilli i. Bacillus 1. Spore forming 2. Aerobic 3. Catalase POSITIVE 4. Persist in soil 5. Types a. B. Anthracis i. Spores- bamboo appearance ii. Non-beta hemolytic iii. Non-motile iv. Has a capsule v. Pulmonary disease- shows widened mediastinum ii. Corynebacteria 1. Irregular shape (Chinese letter shaped) 2. Catalase positive 3. Causes Diptheria iii. Listeria Monocytogenes 1. Tumbling motility 2. Non-spore forming 3. Beta-hemolytic 4. Diseases a. Meningitis b. Endocarditis c. Neonatal infection d. Infection in pregnant women 2. Antibiotics a. Beta Lactams i. Inhibit crosslinking of peptide side chains in bacterial cell walls ii. BacterioCIDAL iii. Safe in pregnancy

1. 2. 3. 4.

iv. Renally cleared v. Resistance 1. Beta lactamases 2. Changes to the binding site (MRSA) vi. Adverse effects: Rash (anaphylaxis), hematologic toxicity vii. Includes: 1. Penicillins a. Doesnt go to prostate or intraocular fluid (otherwise good distribution) b. Renally cleared (so careful in kidney failure) c. Synergize with aminoglycosides d. Beta Lactamase inhibitors i. Clavulanic acid, sulbactam, tazobactam ii. Add anaerobic coverage 2. Cephalosporins a. Renally excreted b. 1st and 2nd gen do NOT penetrate CSF c. Doesnt cover enterococci, lysteria, MRSA d. Adverse reactions: Rash, fewer platelets, fewer WBC e. First Generation cephalosporins i. The Surgeons favorite ii. Covers gram positive iii. Skin, soft tissue infection; surgical prophylaxis iv. Includes: 1. Cefazolin, cephalexin f. Second Generation i. Sinusitis, Otitis ii. Works against Haemophilus iii. Covers more gram negative, strict anaerobes iv. Includes: 1. Cefoxitin g. Third Generation i. More gram negative ii. Stable to beta lactamases iii. Ceftazidime Pseudomonas aeruginosa iv. Ceftriaxone gram POSITIVEs. Meningitis, community pneumonia h. Fourth Genreation i. Gram positive and negative ii. Cefepime pseudomonas, gram negative resistant bacteria i. Fifth generation i. Covers MRSA

3. Carbapenems a. Stable to beta lactamases b. Gram positive and negative i. Including pseudomonas c. Reserve for serious infection d. Imipenem; meropenem; ertapenem (doesnt do p.aeruginosa) 4. Monobactams a. Only gram negative i. Including pseudomonas b. Can use in penicillin allergic pts c. Azetreonam- IV b. Vancomycin i. Inhibits elongation step of cell wall synth ii. Only gram positive iii. Not absorbed orally. Used in C. Diff Colitis iv. Renal clearance v. Measure trough levels vi. Adverse effects: Red Man Syndrome, renal toxicity, hemotologic, ototoxicity vii. Use for: 1. MRSA (hospital acquired) 2. Beta lactam allergies 3. Second line for staph/strep endocarditis 4. C. Diff Colitis c. Oxalidinones (Linezolid) i. Inhibits protein synth (binds to 50s subunit) ii. Gram positive iii. Weak MAOinhibitor. So can get serotonin syndrome with SSRIs iv. Adverse effects: headache, nausea, thrombocytopenia, peripheral and optic neuropathy. v. Use for: 1. MRSA, VRE vi. Very expensive vii. Reserve d. Daptomycin i. Depolarizes cell walls ii. bacterioCIDAL iii. gram positive 1. MRSA, VRE 3. Antibiotics II a. Aminoglycosides i. Enter bacterial cells ii. Bind irreversibly, Inhibit 30s ribosome

BacterioCIDAL Renally exreted Resistance due to inactivating enzyles Narrow therapeutic index 1. Monitor peak and trough vii. Adverse effects: Nephrotoxicity, ototoxicity viii. Use for gram negative bacilli, staph, mycobacteria. 1. No anaerobes ix. Use for synergy x. Includes: Gentamycin (gram pos cocci), streptomycin (TB, plague) b. Tetracylcines i. Bind reversibly to 30s, inhibiting protein synth ii. bacterioSTATIC iii. must be transported into cell iv. resistance: changes in transport v. does not penetrate CSF vi. milk, antacids decrease absorption vii. contraindicated in pregnancy 1. cross placenta, affect fetal bones, teeth viii. works for intracellular pathogens 1. Chlamydia, mycoplasma, legionella (causes of atypical pneumonia) 2. Rickettsia (doxy), lyme disease, STDs ix. Includes: 1. Tetracycline, Doxycycline, Minocycline x. Adverse effects: 1. Gastric irritation, nausea, vertigo, photosensitivity, diarrhea c. Tigecycline i. A bigger, better tetracycline ii. Overcomes resistance iii. Use for resistant gram positive, resistant gram negative , anaerobes, mycobacteria 1. Not pseudomonas iv. Like tetracycline 1. Also contraindicated in pregnancy 2. Also causes photosensitivity d. Macrolides i. Bind reversibly to 50s ii. BacterioSTATIC iii. Metablolized in LIVER 1. Cyt P450. Lots of interactions iv. Doesnt penetrate CSF v. Includes: 1. erythromycin, clarithromycin, azithromicin, dirithromycin.

iii. iv. v. vi.

vi. Use for: mostly gram positive, some gram neg 1. Not pseudomonas 2. Erythro- staph, strep, atypical pneumonias 3. Community acquired pneumonia vii. Adverse effects: GI toxicity (frequent), warfarin interaction (bleeding) e. Lincosamides (clindamycin) i. Covers grampositive, and anaerobes 1. no gram neg ii. metabolized in LIVER iii. does not penetrate CSF iv. use for: 1. community MRSA 2. bacterial vaginosis 3. staph, strep f. Quinolones i. Block DNA synthesis by inhibiting gyrase, topoisomerase ii. Absorbed very well orally iii. Renally excreted iv. Enters the prostate (use ciprofloxacin) v. Contraindicated in pregnancy 1. Can cause tendonitis, tendon rupture vi. Adverse effects 1. CNS, arthropathy, photosensitivity vii. Fluoroquinolones 1. Ciprofloxacin- for gram negatives, a. Only oral option for pseudomonas b. No anaerobes c. Worsk for intracellular pathogens d. Use for: i. UTIs, Prostatitis, bacterial diarrhea, some STDs, anthrax 2. Moxifloxacin and levofloxacin a. Expand gram positive coverage i. Use for: Bronchitis, community pneumonia g. Nitroimidazoles i. Anaerobes, some parasites ii. Is reduced to cyctotoxic intermediates that inhibit DNA synthesis iii. Includes METRONIDAZOLE 1. Good oral absorption 2. Enters CSF, BRAIN 3. Use for: a. Anaerobic infection, brain abscess, c.diff colitis, bacterial vaginosis; giardia, trichomonas, amoeba

4. Adverse effects: nausea, metallic taste, seizures, peripheral neuropathy, antabuse effect h. Sulfonimides i. Dont use alone, everythings resistant. 1. Use with trimethoprim. Both inhibit steps in folate synth ii. Gram positives, some enterobacteraciae 1. Use for: nocardia, toxoplasmosis, pneumocystis iii. Adverse effects: Hypersensitivity (HIV), hemolytic anemia, Jaundice, neutropenia i. Trimethoprim i. Penetrates prostate 1. Use for prostatitis, certain UTIs j. Trimethoprim Sulfamethoxazole (TMP-SMX) i. Synergistic ii. bacterioCIDAL iii. used in HIV pts iv. covers gram positives some gram neg. v. use for: pneumocystis, toxoplasmosis, nocardia, uncomplicated UTI, prostatitis, some STDs, MRSA (outpatient. Its oral) 4. Endocarditis, bloodstream infections a. Bloodstream infection classification i. 2 infection: from another infected site ii. 1 infection: from an unknown site 1. Catheter 2. Endocarditis iii. Transient b. Diagnosis of CA- BSI i. Clinical picture ii. Get blood cultures iii. No evidence of infection elsewhere c. Tx i. Remove catheters if possible ii. Treat 7-14 days if uncomplicated, 1. 4-6 weeks if complicated (endocarditis, supperative thrombophlebitis, osteomyelitis) iii. Risk factors 1. Imm supp 2. Neutropenia 3. CHF 4. DM 5. Being fed through the catheter (TPM) 6. Catheter scenario, location, type iv. Complications

1. Endocarditis 2. Osteomyelitis 3. Endopthalmitis 4. Septic arthritis 5. Septic pulmonary emboli 6. Systemic abscesses d. Endocarditis i. Usually infects valves ii. Pathophysiology 1. Native valves with underlying disease 2. damage of valve with fibroblast healing 3. transient bacteremia 4. colonization of valve 5. growth of vegetation iii. If untreated, fatal. If treated, still probably fatal iv. In a native valve, its usually oral strep or staph aureus v. In IVDU, Its usually s.aureus vi. In prosthetic valve, EARLY, its coag neg staph. LATE its oral strep vii. Culture negative endocarditis 1. HACEK organisms a. Hard to culture b. Haemofilus c. Actinobacillus d. Cardiobacterium e. Eikenella f. Kingella viii. Clinical picture: 1. Fever, chills, cardiac murmur, arthralgia/myalgia, 2. Vascular signs a. Osler nodes- tender nodules on fingers i. Indicate chronic endocarditis ii. Autoimmune vasculitis b. Splinter hemorrhages- in the fingernail (usu near base) c. Janeway lesions- look like bruises i. Palms and soles ii. Contain bacteria d. Roth spots- retinal spots e. Petechiae- hemorrhages on conjunctiva ix. Diagnosis: 1. 2 major criteria: microbiologic (blood culture), evidence of endocardial involvement

2. Minor criteria: predisposition, fever, immunologic/vascular phenomenon, microbiologic 3. Trans Esophageal Echo is gold standard x. Embolic complications 1. Stroke 2. Brain abscess 3. Lung abscess 4. Spleen problems 5. Kidneys xi. Tx: based on organism 1. Empiric Vanc + gentamycin + ceftriaxone 2. Use penicillin if sensitive 3. Treat for 4-6 weeks 4. Surgery if necessary a. Valve insufficiency causes CHF b. Persistent sepsis c. Valve ring/myocardial abscess d. Others xii. Prophylaxis for IE 1. Dont use for most patients 2. Consider if: a. Prosthetic valve b. Previous IE c. Heart transplant with a valvulopathy d. Unrepaired cyanotic shunt e. NOT Mitral valve prolapsed 5. Skin and soft tissue infections a. Impetigo i. Mostly in kids ii. Superficial intraepidermal vesicles iii. Crusty, weeping iv. Caused by : Group A strep or Staph Aureus b. Folliculitis i. Inflammation of hair follicles ii. S. aureus is common. Pseudomonas from pools, hot tubs c. Furuncle i. In areas of friction, perspiration. Contain hair follicles ii. A red tender nodule of pus iii. Risk factors: Obesity, neutropenia, DM, steroids d. Erysipelas i. Clearly demarcated, slightly raised area. Peau dorange ii. Older adults, kids

e.

f.

g.

h.

i.

j.

k.

l.

iii. Lower extremity iv. Caused by: group A strep v. Venous stasis, lymphatic obstruction, DM, alcohol abuse Cellulitis i. More diffuse border, not raised ii. Secondary to trauma, other lesion iii. Hot, tender, swollen iv. Fever, malaise, chills, leukocytosis v. Caused by: staph aureus or any strep vi. Drug of choice is vancomycin Necrotizing Faschiitis i. Effects extremities mostly ii. Erythematous, hot, painful, no defined borders (initially) iii. Fever, leukocytosis positive gram stain iv. Changes quickly: red-purpleblue-graygangrene v. Loses feeling (doesnt hurt anymore) vi. Fourniers Gangrene 1. In males. Involves scrotum, perineum 2. Multiple bacteria vii. Tx: Surgical debridement, antibiotics Pyomyositis i. Infection, abscess of muscle ii. Immunocompromised, following blunt trauma iii. Usu Staph Aureus Community acquired MRSA i. Has the P-V Leukocidin ii. Usu cutaneous iii. Use vanc, I guess. Lots of options Vibrio Vulnificus i. Liver disease + ingest raw shellfish ii. Necrosis in arms, legs. May need amputation iii. Doxycycline is drug of choice Cutaneous Anthrax i. Direct contact ii. Prurituspainless papule vesicle painless necrotic ulcer with black center iii. Treat with Ciprofloxacine or Doxyfloxacine for at least 60 days Acute lymphangitis i. Tracks up lymphatics ii. Seen with Pasteurella (cat bites), Group A strep Mycobacterium Marinum i. Open wounds exposed to freshwater/aquariums ii. Subacute/chronic cellulitis

iii. Lesions track up lymphatics m. Toxic Shock mediated disease i. Fever, nausea/vomiting, diarrhea, confusion ii. Staph Aureus (mortality LOW) or Group A strep (mortality HIGH) iii. Desquamating rash n. Scalded skin syndrome i. Begins with a known infection ii. Treat with Vanc 6. Bacterial Pneumonia a. Risk factors i. Disruption of barriers (anatomical, mechanical) 1. Smoking 2. CHF 3. COPD, Asthma ii. Increased exposure to pathogens 1. Crowding 2. Aspiration iii. Immune Deficiencies 1. Infant not breastfeeding 2. Very old 3. DM 4. HIV iv. Iatrogenic manipulations 1. Bronchoscopy 2. Sedation 3. Immunosuppression b. Clinical picture i. Fever, productive cough, pleuritic chest pain ii. Tachypnea, rales, leukocytosis (mostly band) c. Strep pneumoniae i. most common cause of CAP ii. can kill you iii. most damage is caused by the inflammatory response it creates iv. remember: polysaccharide capsule, diplococcus v. Tx: Ceftriaxone d. H. Influenza i. Chronic lung disease ii. Gram neg coccobacillus iii. Makes a weak beta lactamase. iv. So use 2nd gen cephalosporin e. Moraxella i. Gram neg diplococcus (just like neisseria)

ii. Colonizes nasopharynx. When it spreadsdisease f. Staph Aureus i. Severe Necrotizing pneumonias in healthy kids ii. Pleural effusions, empyema iii. CA-MRSA common. Has P-V leukocidin iv. Tx: Vanc g. Atypicals: Chlamydia, legionella, mycoplasma h. Diagnosis: i. Blood culture, sputum culture ii. CXR iii. O2 sat i. Tx: i. Supportive: 1. Blood pressure (IV fluids, pressors) 2. Ventilatory support (mechanical ventilation, O2 ii. Antibiotics 1. First empiric 2. Then pathogen-directed j. Hospital Acquired Pneumonia i. 48-72 hours after admission ii. Usu resistant bacteria (oft gram negative) 1. Enterobacteriaceae, pseudomonas, staph aureus iii. Dx: Sputum gram stain and culture iv. Tx: empiric, broad spectrum 7. Sepsis a. SIRS: i. Temperature too low or high ii. HR>100 iii. RR> 20/min iv. WBC over 12,000 or under 4000 v. Very easy to have this, just by walking up some stairs b. SIRS + infection = sepsis c. Sepsis + 1 sign of organ failure = severe sepsis d. Sepsis + inability to keep adequate blood pressure despite fluids = septic shock e. Mostly caused by gram positive organisms i. Fungi have been increasing f. Pathogenesis i. Endotoxin binds to immune cell cell makes inflammatory cytokines (IL-1, IL-6, TNF 1. fever, tachypnea, tachycardia 2. capillary leak, neutrophil migration, platelet aggregation 3. vasodilation

ii. inadequate blood pressure iii. Lactic acidosis death iv. Hyperreactive immune response to LPS 1. Binds to TLRs a. TLR4 does gram neg b. TLR2 does gram pos i. Gram pos sepsis is usually staph aureus 1. Uses peptidoglycan instead of LPS g. Diagnosis i. At least 2 blood cultures 1. One from each central line, if present ii. Remember, its not always infectious h. Tx i. Early antibiotics, broad spectrum ii. Pick based on clinical presentation (transplant? Neutropenic? HIV?) iii. Drain pus, debride tissue, remove infected material iv. Activated Protein C 1. Anticoagulant, antiinflammatory 2. Expensive, bleeding risk v. Corticosteroids 1. Debated vi. Maintain normoglycemia in dm pts 1. Just keep it reasonable 8. Atypical Pneumonia a. Typical vs Atypical Typical Atypical Onset Sx acute fever, cough, chest pain severe rales, consolidation insidious Fever, cough, headache moderate minimal rales scant, clear mild interstitial none

Constitutional Sx Physical findings Sputum Leukocytosis CXR

purulent, rust colored common airspace disease

Response to penicillin prompt

b. Causes: i. Mycoplasma pneumoniae 1. Lacks cell wall 2. Contains membrane sterols 3. fried egg appearance on microscope 4. Long replication time 5. School-aged kids, with pneumonia visible on Xray 50% chance its mp 6. Infects mucus membranes of respiratory tract a. Not alveolar, Its AIRWAY 7. Diagnosis is clinical 8. Tx: macrolides (azythromycin) ii. Chlamydia pneumonia 1. Looks similar to m.penumoniae 2. May have a long duration. 3. Mild sx 4. Tx: macrolides (azythromycin) iii. Chlamydia psittaci 1. Chlamydiae are obligate intracellular 2. Nuclear inclusions seen 3. Psittaci is related to parrots iv. Legionella pneumophila 1. Many strains now 2. Fastidious growth requirements 3. Found in aquatic environment 4. Likes warm 5. Lives within amoebas 6. Chlorine resistant 7. No person to person transmission 8. May appear to have multisystem involvement 9. Dx test: sputum culture 10. Tx: Azythromycin v. Viral pneumonias 1. Esp in kids 2. Seasonal 9. Gastroenteritis a. Mechanisms of pathogens i. Secretory toxin: inhibit absorption, enhance secretion (cholera) ii. Cytotoxins: destroy absorptive cells, giving diarrhea (shiga toxins, c.diff) iii. Invasion: Burrow into mucosa, inhibit structural resorbing ability (campylobacter) iv. Neurotoxins: vomiting predominates. Bug may be dead already (staph enterotoxin) b. Sx: i. Vomiting toxin, virus

ii. Nonbloody diarrhea small bowel dysfunction (shigella, salmonella) iii. Bloody diarrheabacterial colitis, colon c. Cholera i. Water-borne ii. Toxins: 1. cholera toxin a. A subunit: ADP ribosylase i. Translocates into cell/causes harm to cell b. B subunit: GM1 ganglioside i. Docking mechanism. Highly immunogenic c. Locks adenylate cyclase in ON position i. Enhances cAMP levels ii. Enhances Cl secretion 2. pili (attachment) iii. They lose 1-2 LITERS of stool per HOUR iv. Tx: Rehydration 1. Water + salt + sugar d. E.Coli diarrhea i. Enterotoxigenic Ecoli- travellers diarrhea 1. Secretory diarrhea cholera-lite 2. Harms kids more than adults 3. antiBio may help, but NOT prophylaxis ii. Enteropathogenic Ecoli- severe infantile diarrhea iii. Enteroinvasive Ecoli- like shigella iv. Enteroaggregative Ecoli- chronic diarrhea v. Enterohemorrhagic Ecoli (produces shigatoxin)- Ecoli o157:H7 1. Can be lethal 2. In foods often (rare burgers) 3. Can give hemorrhagic colitis a. Toxins in bloodstream injure endothelial cells b. Form clots c. Frickin everywhere. 4. Hemolytic uremic syndrome e. Rotavirus i. Has a capsid ii. Nearly everyone gets some rotaviral infections as a kid iii. The first one is worst iv. It can kill children v. Vaccine: they made one, but it had intussiception risk not acceptable in us 1. So other countries (where it couldve saved kids lives) also didnt accept it. f. Giardia i. Carried in water

ii. Non-bloody chronic diarrhea iii. Treat with metronidazole g. Entameba histolytica i. Amebiasis ii. Rare in US. iii. Tx with metronidazole h. Cryptosporidium parvum i. Severe chronic non-bloody diarrhea ii. Even in immune competent ppl iii. Treat with nitazoxanide i. C. Diff i. Healthy ppl often carry it ii. Culture is tedious. DONT. just test for toxins iii. Pseudomembranous colitis iv. Tx: Vancomycin 10. Urinary Tract Infections a. Clinical syndromes i. Bacteuria- bacteria in urine that shouldnt be there ii. Acute cystitis 1. Most common 2. Voiding syndrome a. Burning urination b. Feeling like you need to go all the time c. Suprapubic tenderness d. Occult URI iii. Pyelonephritis- upper tract infection 1. Flank pain 2. Fever, chills 3. Nausea, vomiting iv. Renal abscess 1. Abscess around/in kidney 2. From untreated pyelo 3. Can give fever of unknown origin v. Uncomplicated UTI- UTI involving normal urinary tract with no functional problems vi. Complicated UTI- everything else b. Epidemiology: more in women then men i. Women: starts medium, rises after sexual activity ii. Men: starts low (neonate), drops to zero, rises after age 45 c. Caused by: i. Uncomplicated: 80% E.Coli 20% proteus, enterobacteraciae ii. Complicated: 20% e. coli 80% klebsiella, enterobacteraciae, pseudomon d. Mostly ascending (90%)

e. Pathogenesis i. Vaginal colonization happens first ii. Entry into urinary tract iii. Bacterial virulence 1. Adherence 2. Toxins 3. Capular polysaccharides 4. Urease production iv. Host Defense 1. Colonization resistance from urogenital flora 2. Antimicrobial properties of urine 3. Inflammatory response- leads to turnover and sloughing of infected cells 4. Micturition, bladder emptying gives mechanical protection 5. Specific immune responses 6. Barrier method contraception increases risk v. Risk factors for worse outcome 1. Infants, Kids 2. Pregnant women 3. Compromised adults: DM, imm comp, spinal cord injury f. Diagnosis i. Internal dysuria, other voiding sx, abrupt onset, no vaginal discharge ii. Urinalysis, microscopy 1. If you dont have pyuria, you dont have cystitis iii. Leukocyte esterase test 1. If negative, they dont have UTI (checks for pyuria) iv. Nitrite test 1. Specific but not sensitive g. Tx: Bactrim (TMP/SMZ) for 3 days (uncomplicated) i. 7 days if risk factors ii. 14 days for men h. Acute uncomplicated pyelonephritis (women) i. Usu ecoli ii. Pyuria present iii. Tx: fluoroquinolones iv. Culture after therapy is over i. Recurrent UTI i. Relapse/reinfection ii. Change contraception iii. Cranberry juice? iv. TMP/SMZ prophylaxis 11. Anaerobic Infections a. Gram Negative:

b.

c.

d.

e. f. g.

i. Bacteroides (esp fragilis) 1. Give the most greif Gram Positive i. Peptostreptococcus ii. Clostridium iii. Lactobacillus Live in mucosal surfaces and GI tract i. Not in stomach ii. Predominate in colon Hallmarks i. Suppuration ii. Abscess iii. Thrombophlebitis iv. Chronic v. Polymicrobial (synergy) vi. Gas formation vii. Lowered blood supply predisposes viii. Infection adjacent to mucosal tissue ix. Smells like feces x. Virulence factors: Exotoxins (clostridium), Capsular polysaccharides, beta lactamase (bacterioides fragilis) Specimens necessary i. Blood, aspirates, pus, deep tissue. No swabs Tx: ampicillin-sulbactam (include a beta lactamase inhibitor) i. Drain, debride Diseases caused i. Head and neck infection 1. Ludwigs angina (neck spaces) 2. Lemierres syndrome (septic thrombophlebitis of jugular vein) 3. Gingivitis, dental abscess, to mandible ii. CNS 1. Solitary brain abscessanaerobe 2. Spreads from chronic otitis, mastoiditis, sinusitis 3. Tx: metronidazole plus ceftriaxone iii. Pulmonary infection 1. Aspiration of oral flora 2. Necrotizing pneumonia, abscess, empyema 3. Tx clindamycin iv. Intraabdominal infection 1. Perforation a. You need surgery b. Treat with combos (polymicrobial)

v. Pelvic infection vi. Skin, soft tissue 1. Gas gangrene, nec fasc 2. Deep tissue involvement 3. Aggressive debridement, antibiotics h. Clostridium Difficile i. Gram pos, spore forming, anaerobe ii. All over hospitals iii. Causes pseudomembranous colitis iv. Really bloody diarrhea v. Toxins A, B- cytoskeleton injurymucosal injuryfluid secretion vi. Culture not useful vii. Complications 1. Fulminant colitis, perforation, toxic megacolon viii. Tx: oral vanc i. Clostridium perfringens i. Gas gangrene, myonecrosis, nec fasc ii. Enterotoxin (food poisoning) iii. Aggressive deridement iv. Penicillin + clindamycin j. Clostridium tetani i. Preventable ii. Toxin- tetanosporin. Stops inhibition of motor neurons k. Clostridium Botulinum i. Foodborne ii. Descending paralysis (prevents Ach release) iii. Makes 7 neurotoxins l. Actinomycoses i. Gram positive branching bacillus 1. Looks like a fungus but is NOT 2. Not acid fast (unlike nocardia) ii. Sulfur granules in tissues iii. Extends through tissue planes like malignancy iv. Tx: penicillin 12. Arboviruses, Enteroviruses a. Arthropod-borne viruses b. Potential for explosive epidemics c. Humans are dead-end hosts d. Usual vectors: mosquitoes, ticks, fleas e. Dengue fever i. Most important flavivirus ii. Mosquito borne (aedes aegypti)

Distributed in a belt across the world: tropics, subtropics Get infected and reinfected. Sequentially worse. breakbone fever- fever, rash, HA, severe myalgia, arthralgia Heals with no sequelae unless Dengue shock syndrome- 3rd space fluid into lungs, abdomenhypovolemic No treatment It takes less than 2 weeks to show up (so if travel was more distant than that, dont worry) f. West Nile i. Normally between birds and mosquitoes ii. Epidemiology: over 55 higher risk iii. Fatality is worse for hospitalized pts iv. Genetic susceptibility: CCR5 mutation v. Pathogenesis 1. Bitten by mosquitotravels to lymph nodeviremiaCNS 2. If high enough innoculum, can cross BBB, kill neurons vi. 5-10 days after mosquito bite vii. Mild: fever, headache, myalgia/arthralgia, anorexia viii. Sore throat ix. Rash (trunk> extremities) (rare in US cases) x. Recovery is usu complete, worse in adults than kids xi. Tx: no real tx g. Chikungunya virus i. Mosquito borne (aedes aegypti) ii. Debilitating febrile illness (joint pain impossible to move) iii. No vaccine/tx iv. Possibility of pandemic h. Enteroviruses i. Many serotypes ii. Usu infections are mild: febrile rash, UTI iii. Very small iv. Non-enveloped v. Have a protein coat 1. So hard to decontaminate. Alcohol wont help here vi. Mostly in summer and fall vii. Mostly in young kids viii. Transmission: fecal-oral, respiratory droplets ix. Adults have more severe disease x. Men 2X xi. Can make vaccines (it worked for polio), but theyre so small, they can be synthesized. xii. Diseases caused

iii. iv. v. vi. vii. viii. ix.

1. Aseptic meningitis a. Coxsackievirus group B b. Summer and fall meningitis 2. Encephalitis a. Altered mental status, focal neurological signs, seizures b. Worse prognosis than aseptic meningitis c. Enterovirus 71 3. Cardiac disease a. Acute myocarditis in young ppl (esp males) i. Enteroviruses, coxsackie b. Chronic cardiac disease i. Sporadic dilated cardiomyopathy ii. Coxsackie group B 4. Eye infections a. Acute hemorrhagic conjunctivitis b. Excessive lacrimation, pain, periorbital swelling, redness, visual impairment 5. Respiratory syndromes a. Enteroviruses- cause URI 6. Herpangina a. Febrile illness, acute onset, sore throat i. Lesions on tonsils, soft palate, uvula, pharynx ii. May be part of hand-foot-mouth 7. Hand-Foot and Mouth disease a. Common in kids b. Very contagious xiii. Therapy: supportive care 13. DNA Viruses (Herpes) a. Double-stranded, enveloped DNA virus b. Gene expression i. VP16 stimulates transcription of IE genes (doesnt require protein synth) ii. IE genes code for proteins that stimulate Early Gene expression iii. Early Genes encode nonstructural proteins that help DNA synthesis iv. DNA replication occurs v. Late Genes are expressed, genes for structural proteins c. Latency i. Virus persists for life as an episome (limited viral gene expression, noninfectious) ii. Latency is failure to stimulate IE gene expression iii. Reactivation may or may not have signs and sx d. Transmission- direct contact w body fluid i. Does not survive in environment ii. Mucosal surfaces, resp tract, bloodstream are susceptible sites

e. HSV 1 and 2 i. HSV1 1. 2. 3. 4. 5.

f.

Orolabial Usu get it in childhood Up to 90% of adults have it (higher levels in poorer ppl) 20-40% recur Course: a. Primary infection- most widespread i. Fever, malase, myaglias ii. Lesions on palate, lips, tongue b. Latent- noninfectious HSV in the trigeminal ganglion c. Recurrence i. 20-40% in first year ii. More limited iii. Triggered by: trauma, light, imm suppression 6. Incubation is from 2-14 days 7. Many people are asymptomatic carriers ii. HSV 2 1. Genital 2. Sexually transmitted 3. 25% of adults have it 4. 60-90% recur 5. Painful lesions 6. Primary infection can have systemic sx (like HSV1) 7. Incubation period of 2-7 days 8. Virus can be shed asymptomatically iii. Diagnosis: 1. Viral isolation iv. In Imm Comp 1. Reactivate frequently 2. Can involve other systems (gi, etc) 3. Is a prominent feature in advanced HIV v. Tx 1. HSV1- analgesics, acyclovir (esp if recurrent) 2. HSV2- also acyclovir vi. Encephalitis 1. Most common endemic encephalitis in US 2. Usu caused by HSV1 3. Can happen at any age 4. Dx: CSF PCR. MRI if you want 5. Tx: high dose acyclovir for 3 wks Varicella Zoster virus

i. Spread by direct contact ii. Primary infection: Chicken pox 1. 5-9 yo 2. Respiratory spread 3. Fever, URI, malaise; THEN the rash a. By the time you have the rash, youre not contagious 4. Rash: start on face/head, move down a. Different stages of vesicle will be near each other 5. Tx: Antihistamines, acetaminophen, acyclovir (heals faster, fewer lesions) 6. Vaccine: Varivax. a. Live, attenuated b. Give to kids iii. Recurrent infection: Zoster (Shingles) 1. Follows unilateral dermatomes 2. Pain, burningerythema-papulesvesicles 3. Mostly in older ppl 4. Virus sheds only while theres rash 5. If it crosses dermatomes, its disseminated a. Risk of pulmonary transmission 6. Tx: Acyclovir, analgesics 7. Vaccine: Zostervax a. Live, attenuated b. Give to adults over 60 c. More concentrated form of varivax 14. Herpesviruses 2 a. CMV i. Lipid envelope derived from host ii. Largest herpes virus iii. Infects fibroblasts, endothelial cells, epithelial cells, and macrophages iv. Can be latent in cells of monocyte/macrophage lineage v. Pathophysiology 1. Primary infection- Usu resp tract. Then it disseminates 2. Productive infection- shedding virus from secretions (saliva, urine) 3. Adaptive immune respose-controls the virus 4. Latency- in hematopoetic cells in bone marrow, 5. Reactivation- periodically (from immunosuppression, stress, pregnancy) vi. Interacts with immune response: 1. Inhibits expression of MHC 1 2. Blocks antigen presentation of MHC 2 3. Downregulates NK cells 4. Inhibits TH1 vii. Epidemiology

1. Widespread, requires close contact (person to person) a. Saliva, tears, urine, genital secretions, blood b. Vertical transmission to babies i. Babies are usu asymptomatic ii. more likely to be symptomatic if mom gets CMV during pregnancy. viii. Disease: 1. In a normal host, asymptomatic, or mono-like illness ix. Transplants 1. Solid organ: Donor positive, recipient negative is highest risk a. CMV is common in solid organ transplants b. Just get systemically sick 2. Stem cells: Donor negative, recipient positive is highest risk a. CMV pneumonia is common here i. Bilateral, diffuse, interstitial 3. HIV patients get CMV retinitis x. Dx 1. PCR of blood. 2. Amount of virus corresponds to severity of infection xi. Tx: Gangcylcovir b. Roseola (HHV6) i. Beta herpes virus ii. Infects T lymphocytes iii. Sheds in saliva iv. Everyone gets it within first 3 yrs of life v. High fever, then as fever breaks, develops rash 1. Some kids dont get the rash 2. Can also get febrile seizures vi. Dx: PCR of blood vii. Tx: unsure. Gangcyclovir? c. EBV i. Replicates in B lymphocytes 1. When it infects them, they become immortal ii. Exposure to infected saliva 1. pharyngitis 2. shedding in saliva 3. B cell infection a. heterophile antibodies b. T cell activation i. malaise, spleen enlargement, atypical lymphocytes ii. control the B cell population 1. EBV becomes latent

iii. Transmission: person to person (infected saliva) iv. Diseases 1. Infectious mononucleosis a. Fever, tiredness, lymphadenopathy, sore throat b. Rare complications: autoimmune hemolytic anemia, thrombocytopenia, splenic rupture, encephalitis, meningitis, guillan barre c. Tx: supportive care. Acyclovir has no clinical help. i. Corticosteroids for SEVERE complications 2. Burketts Lymphoma 3. Oral hairy leukoplakia (HIV) d. Kaposis Sarcoma (HHV 8) i. Multiple lesions ii. Multiple cell types iii. Worse risk if imm comp iv. Most ppl are asymptomatic v. If youve had it before, then get AIDS, Kaposis is more common vi. Dx: PCR, histology vii. Tx: HHV8 is sensitive to foscarnet. 1. Unclear clinical use 15. Respiratory viruses a. Often seasonal i. RSV: in the WINTER ii. Influenza: in the WINTER iii. Rhinovirus: in the SPRING and FALL b. Most common respiratory virus is rhinovirus c. Rhinovirus i. Non-enveloped 1. Stable in the environment ii. Spring and fall peaks iii. Transmitted by particle aerosol, or secretions iv. Mostly young kids v. Pathogen of upper respiratory tract 1. Causes common cold 2. Can also go down into lower airways and cause asthma exacerbations vi. Non-cytopathic vii. Dx: clinical viii. Tx: symptomatic. Antihistamines, NSAIDS d. Influenza i. Enveloped ii. Segmented RNA genome 1. H and N

iii. iv. v. vi. vii. viii. ix. x.

2. Can recombine (antigenic shift) Main reservoir is birds (its a zoonosis) Seasonal (winter) Airborne transmission (doesnt require close contact) Sx: Fever, malaise, cough, sore throat, feel awful Cytopathic- damages respiratory epithelium Dx: Viral culture Tx: Neurominidase inhibitors Vaccine 1. Live attenuated (nasal spray) 2. Inactivated (injection 3. Grown in eggs 4. Reformulated yearly

e. RSV i. Enveloped ii. RNA virus iii. Everyone gets it in first 2 yrs of life 1. 1% need hospitalization 2. Can get reinfected (immunity is incomplete) iv. Transmission by large droplets, contaminated secretions v. Sx: Bronchiolitis, pneumonia 1. Premies- apnea 2. Preexisting heart conditions- decompensation vi. Pathophysiology 1. Infection of respiratory epithelial cells a. blockage of airways (edema, cellular debris) b. asthma-type sx (air in, but cant escapehyperexpansion) c. Cell mediated immunity clears it vii. Dx: nasopharyngeal aspirate/swab 1. Antigen test viii. Tx: mostly symptomatic (o2, hydration, ventilation if needed) 1. Ribovirin for imm comp 16. Antiviral agents a. Herpes drugs i. Topical: 1. trifluorothymidine a. Drug of choice for hsv keratoconjunctivitis 2. Cidofovir a. Very toxic b. Used for resistant strains of DNA viruses (CMV, HSV, EBV, VSV) i. For immunocompromised, before it disseminates 3. Docosanol

a. Over the counter. b. Recurrent HSV ii. Systemic 1. Require phosphorylization inside the cell 2. Acyclovir a. Inhibits DNA polymerase b. Prefers HSV DNAp to host DNAp c. Use for HSV, VZV (VZV requires higher doses) d. Adverse effects: rare, reversible i. Watch out for CNS (confusion, seizures. More in elderly) 3. Valacylcovir a. Prodrug of acyclovir b. 4X more bioavailable 4. Famicyclovir (prodrug), penicyclovir a. Same action as acyclovir. b. Also, hep B c. Famicyclovir = oral; penicyclovir= topical 5. Gancyclovir a. For HSV- same efficacy as acyclovir b. CMV- 10-50X BETTER c. Competitive inhibitor of DNAp d. Use for: serious CMV infections, transplant prophylaxis e. Renally cleared f. Lots of toxicity i. Neutropenia, anemia ii. Bone marrow suppression 6. Valcancyclovir a. Prodrug b. Oral availability equals IV! (high serum levels) iii. Foscarnet 1. Non-nucleoside inhibitor 2. Doesnt require phosphorylation 3. Directly inhibits herpes DNAp 4. Use for resistant strains esp resistant herpes 5. IV only 6. Very toxic a. Nephrotoxic (renally clearedrenal tubular injury) b. Hypo/hyper calcemia, hyperphosphatemia c. Penile ulcers b. Influenza virus i. Vaccine is most important ii. Prophylaxis if not

iii. Neurominidase inhibitors 1. Zanamivir, Oseltamivir a. Work for influenza A and B b. Prevent release of virus particles (so new cells arent infected) c. Few side effects d. Expensive e. Only shortens illness by a few days f. Theres resistance to oseltamivir iv. (and amantidines, but resistance is common) v. Ribavirin 1. Only use for Hep C a. This plus interferon is the treatment 2. Resistance is rare 3. Inhibits viral mRNA formation 4. Can use the aerosol for RSV pneumonia 5. Contraindicated in pregnancy 6. Can get concentrated in RBCshemolytic anemia vi. Interferon-inhibits viral replication 1. Adverse effects: fever, chills, acute pneumonia chronic fatigue, depression, ataxia 17. Acid Fast Organisms a. Lipid rich wall i. Allows for: resistance to drying, antibiotics, detergents b. Penetrates macs, lives freely in them c. M. Tuberculosis i. Rates 2x men ii. Crowding, poverty iii. HIV, Silicosis, IVDU, DM, end stage renal disease iv. Person-to-person (small aerosolized droplets) v. Latent TB 1. Positive skin test/assay 2. No signs/sx 3. Not infectious vi. TB 1. Caseating, granulomatous, usu upper lobes vii. Pulmonary TB Reactivation 1. Cough, hemoptysis, weight loss, night sweats 2. Primary: hilar nodules viii. Extrapulmonary TB 1. Pleuritis- hurts to breathe 2. Lymphadenitis- more WOMEN. Maybe no systemic sx 3. Ostomyelitis- the spine. May have cold abscess of psoas

ix. Military TB 1. Lymphohematogenous spread 2. Can happen in infants x. TB skin test: test sucks 1. Measure area of induration 2. 5mm: a. Past TB pts b. Close contacts of TB pts c. HIV pts 3. 10 mm a. IVdrug use b. Healthcare workers c. Ppl with risk factors d. Immigrants from endemic countries 4. False negatives- due to anergy 5. False positives- BCG vaccine xi. IFNGamma Release Assays 1. Drug of choice for ppl with BCG vaccine 2. More specific 3. Doesnt require return for reading 4. Results in 24 hrs xii. Anti TB drugs 1. Isoconazid a. Interferes with mycolic cell wall synth b. Hepatotoxicity, renal toxicity 2. Rifampin a. Inhibits DNA dependent RNA polymerase b. Adverse rxns: Hepatitis, hypersensitivity, Drug interactions (cyt P450) 3. Rifabutin a. Similar mech to rifampin b. Fewer drug interactions c. Better to use in HIV 4. Pyrazinamide a. Adverse effects: nausea, hepatotoxicity, hyperuricemia, arthralgias 5. Ethambutol a. Inhibits cell wall synth b. Adverse effects: optic neuritis xiii. Treat w all four drugs for 2 mo, INH & rifampin after that, total 6 mo 1. Directly observed therapy xiv. Noninfectious: all of: 1. 3 separate sputum cultures negative

2. Responding to therapy 3. 2 weeks of therapy d. Non-tuberculous mycobacteria i. Hansens Disease (m. Leprae) 1. Tuberculoid a. Low bacterial burden, low infectivity 2. Lepromatous a. High bacterial burden, high infectivity 3. Anesthetic plaques 4. Sensory/motor neuropathy 5. Prefers cooler skin 6. Does NOT grow in culture ii. Nocardia 1. Found in soil 2. opportunist 3. Skin, lung, brain 4. Tx: TMP-SMX 5. Branching, filamentous iii. Rhodococcus 1. Found in soil 2. Opportunist 3. Exposure to horses 4. Grows red on culture 5. Causes cavitary pulmonary disease in imm comp 6. Tx: Vanc 18. STDs: Genital Ulcer Syndromes a. Syphillis i. T. pallidum ii. Difficult to grow iii. Humans sole host iv. Pathogenesis 1. Penetrates skin via microabrasions a. Replicates w/o inflammation b. Travels to lymph nodesblood streamsystemic c. Causes primary lesion at site of inoculation i. Painless ulcer ii. Indurated iii. punched out iv. Scant secretion v. Primary infection: painless ulcer. 1. 3 weeks after exposure vi. Secondary infection: rash on palms, soles. Systemic

vii. Teritary infection: Neuro, CV (ascending aorta), optho viii. Congenital: oft causes stillbirth ix. Tx: Penicillin b. Genital herpes i. Usu HSV2 ii. Initial infection: 1. Systemic: fever, malaise, headache, pharyngitis, myalgias 2. Local: pain, itching, discharge, pyuria, lymphadenopathy iii. Recurs in 80% 1. Has a prodrome (itching, burning) iv. Lesions: 1. Papulevesiclecrustinghealing with no scar v. Dx: viral culture, serology vi. Tx: Acyclovir c. Chancroid i. Haemophilus ducreyi ii. Requires break in skin to infect iii. Pyogenic, painful iv. box car or school of fish appearance histologically v. Disease 1. Genital ulcer 4-7 days post exposure a. Soft, ragged border b. Tender c. Usu multiple d. Painful regional lymphadenopathy vi. Tx: cephtriaxone 19. Candida and antifungals a. Most common is albicans b. Only present where animal contamination is possible c. Present in hospitals d. Grows white on agar e. Human oropharynx, GI tract f. Diseases i. Candidemia 1. Candida isolated from one or more blood cultures 2. Can be a sign of acute disseminated candidiasis ii. Disseminated candidiasis 1. Histologic evidence of tissue invasion AND 2. Culture positive at 2 different normally sterile sites 3. New fever, or septic in a seriously ill person 4. Candiduria (wo catheter) 5. Rash: nonspecific, popular. Can biopsy them and find candida

6. Retinal lesions 7. Lesions in liver 8. Tx: Echinocandin a. Fluconazole for Albicans i. DONT USE if unstable or c. glabrata iii. Vulvuvaginal candidiasis 1. Vaginal discharge a. May just have pruritis, no discharge iv. Thrush, Diaper rash g. Antifungals i. Polyenes 1. Nystatin a. Topical, b/c too toxic to give otherwise 2. Amphotericin B a. Binds to ergosterol in cell membrane b. Increases permeabiliby c. gold standard d. Nephrotoxic e. Lipid preparations i. Less toxic ii. Bigger therapeutic window ii. Azoles 1. Inhibit ergosterol synthesis cells leak 2. Oral a. Fluconazole b. Itraconazole c. Voriconazole d. Posaconazole 3. Topical a. Ketoconazole b. Clotrimazole c. miconazole iii. echinocandins 1. Inhibit cell wall crosslinking (glucans) 2. Used for Candida 3. Well tolerated 4. Expensive 5. IV 6. Includes: a. Caspofungin b. Micafungin c. Anidulofungin

iv. Other 1. Allylamines a. Topical b. Inhibit sterol synth 2. Flycytosine a. Inhibits DNA synthesis b. Treats cryptococcal meningitis c. Bone marrow toxicity 20. Opportunistic Mycoses a. Cryptococcus Neoformans i. India ink stain shows a capsule ii. Encapsulated yeast iii. Narrow-based budding iv. Transmission via inhalation v. Risk factors: SEVERE HIV. CD4 < 50. Less so, other immunosuppression vi. Clinical presentation 1. Meningitis (esp HIV) a. Subacute b. Elevated opening pressure c. High white cells d. Tx: Amphotericin B and Flucytosine, then fluconazole 2. Pulmonary disease: nodules, cavitary lesions, miliary, others 3. Disseminated 4. Skin 5. GI vii. Everyone w/crypto gets an LP 1. Rule out meningitis viii. Tx: AIDS pts: lifelong suppression w fluconazole b. Pneumocystis Jiroveci i. Whispy interstitial infiltrates ii. Cant grow in vitro iii. Transmission via inhalation iv. Seen in: HIV patients (CD4 < 200); corticosteroid pts v. Tx: TMP/SMX, add predisone for serious cases c. Aspergillus i. Septated acute angle hyphae ii. Ubiquitous iii. Fumigatus is most common iv. Can be caused by problems in ventilation. Demolition v. Seen in: Neutropenic pts. Rarely in HIV. vi. Pulmonary: 1. Low grade fever

2. Hemoptysis (sometimes severe) 3. Chest pain 4. Cough 5. Pulmonary infiltrates 6. CXR, CT shows halo sign vii. Non-pulmonary: 1. Sinusitis (w nosebleeds) 2. CNS disease (focal neural signs) 3. Skin viii. Tx: reduce immunosuppression 1. Voriconazole d. Zygomycosis (mucormycosis) i. Grows in the environment (on strawberries 1. Rhinocerebral 2. Pulmonary 3. Cutaneous ii. Risk factors 1. Diabetic ketoacidosis 2. Neutropenia 3. Hematological malignancies 4. Iron chelating therapy iii. Pathogenesis 1. Inhaled (or cutaneous inoculation)direct invasion (nonhemotogenous) 2. Can cross tissue planes 3. Likes vascular invasion iv. Clinical 1. Facial pain, headache, fever 2. Orbital cellulitis, necrosis of the palate, black nasal discharge, proptosis 3. Can also be: Pulmonary, cutaneous, GI v. Dx: Broad, non-septate, right angle branching 1. Culture may be negative vi. Tx: correct risk factors (DKA) 1. debridement. e. Sporotrichosis i. Rose gardens ii. Dimorphic fungi (mold cold, yeast hot) iii. Clinical 1. Lesion at site of inoculation a. Sub Q nodules w/ulceration, may get more in lymphatic distribution iv. Tx: Itraconazole 21. Endemic mycoses a. Histoplasmosis

Dimorphic fungus: outside mold, in the body yeast Mississippi and Ohio river valleys Bat guano, bird roosts Transmission: like TB. Easy to cough out, hangs in air 1. Inhaled v. Pathophysiology 1. Alveolar macrophages engulf it 2. They divide and disseminate in macs vi. Clinical 1. Acute Histoplasmosis a. May be asymptomatic b. Maybe flu-like c. Calcified granulomas indicate past infection 2. Progressive Disseminated Histoplasmosis a. Acute- HIV, imm supp b. Subacute- immunocompetent ppl i. Fever, weight loss, malaise ii. Oral ulcers iii. Hepatosplenomegaly iv. Can look like miliary TB c. Dx: Serology d. Tx: Amphotericin B for severe i. Itraconazole for less severe(drug of choice) 3. Other disease: a. Isolated pulmonary disease i. Cavitary or nodule ii. Can look like TB iii. Check for serology and culture iv. Often in smokers v. Treat with itraconazole b. Aseptic meningitis i. Chronic ii. Serology on CSF iii. Treat with Amphotericin B, then fluconazole c. Mediastinal Fibrosis i. An overaggressive immune response to histo ii. Little treatment d. Erythema Nodosum i. Assosciated with histo b. Blastomycosis i. Broad-based budding ii. Dimorphic fungus

i. ii. iii. iv.

iii. Eastern and central US 1. Waterways iv. Transmission: enters via lungs v. Pathophysiology 1. Incubation- 30-45 days asymptomatic vi. Disease: lung, bone, skin 1. Pulmonary a. Focal lesions 2. Cutaneous a. Get a rash b. Non-healing lesions that ulcerate 3. bone and joint a. Invasive, destructive focal lesions 4. CNS a. Aseptic meningitis vii. Dx: biopsy and culture 1. Serology and urine antigen test arent reliable viii. Tx: itraconazole. Amphotericin B for severe c. Coccidiomycosis i. Dimorphic fungus ii. Spherules full of endospores iii. Southwestern US iv. Risk: Filipino ppl> African American > white v. Transmission: inhaled vi. Disease 1. Most are asymptomatic 2. Nonspecific respiratory illness 3. Infiltrates, hilar adenopathy on CXR 4. Dx: Serology: look for a change from neg to pos vii. Tx: Controversial. Maybe or maybe not treat everyone 1. Definitely treat: a. HIV pts b. Organ transplant pts c. Pregnancy d. Filipino, African ppl 2. Itraconazole viii. Chronic coccidio 1. Chronic fibrotic pneumonia 2. Extrapulmonary a. Cutaneous b. Bone/joint c. Meningitis

d. (sounds like blasto) 3. Dx: Biopsy, culture, serology (titer indicates severity) 4. Tx: we cant cure this like we can blasto and histo a. Chronic suppression b. Amphotericin B initially c. Itraconazole d. Penicilliosis i. Thailand, Vietnam, southern China ii. Dimorphic fungus iii. Opportunistic iv. Clinical: 1. Fever, malaise, weight loss > 4 weeks 2. At least one cutaneous lesion 3. Maybe lymphadenopathy, hepatosplenomegaly, cough v. Dx: Pathology, culture vi. Tx: Amphotericin B, then itraconazole e. Paracoccidiomycosis i. South American Blasto ii. Looks just like blasto, but with more cutaneous lesions, esp face 22. Helminths a. Host specific b. Dont multiply in humans c. Many infections are asymptomatic d. Pathogenesis i. Tissue invasion ii. Compete with hosts for nutrients iii. Create obstructions iv. Incite harmful immune response e. Ascaris Lumbricoides i. Pathophys: 1. Ingest eggs a. Stable in environment b. Fecal-oral 2. Larvae penetrate bloodstream a. Can cause eosinophilic pneumonia 3. Go to lungpenetrate capillariescrawl up airspace 4. Are swallowedlive in intestine 5. Produce thousands of eggs ii. Tx: Mebendazole 1. Binds to tubulin, intefrees with motility 2. Poorly absorbed: so it can hit intestinal worms iii. Southwestern US, Developing countries

f.

Pinworms (enterobius vermicularis) i. Eat eggs ii. Hatch in intestine iii. Live in cecum iv. Adults come out of anus at night to lay eggs v. Dx: scotch tape test- see eggs vi. Many ppl are asymptomatic 1. Treat the whole family g. Whipworm i. Soil transmitted ii. Eat the eggs 1. Barrel shaped, mucus plug at both ends iii. Hatch, live in intestine 1. Produce more eggs into stool iv. More common in: 1. Kids, developing world v. Can cause: anemia, mental retardation, growth delay vi. Blanket tx of all kids with albendazole in developing world h. Hookworm (ancyclostoma duodenale) i. Pathophys 1. Larvae penetrate skin (of foot) (this itches_ a. Travel in bloodstream to lung b. Penetrate capillariescoughed upswallowed c. Reach intestine, penetrate i. Bloody diarrhea, abdominal pain on initial penetration d. Eggs released into stool, hatch in stool e. Larvae can survive in environment for several weeks ii. Disease: Anemia (worse with heavier infection) iii. Tx: Albendazole, mebendazole, and Fe (to help the anemia) i. Cutaneous Larva Migrans i. Because of host specificity of a dog/cat hookworm ii. Serpiginous border of rash. j. Strongyloides stercoralis i. Similar cycle to hookworm, except can cause autoinfection (hyperinfection) 1. Can be very dangerous in immunosuppressed ii. Walking barefoot where there are feces iii. Clinical manifestations 1. Oft asymptomatic 2. Lower abdominal rash (where parasites have entered) 3. Eosinophilia (maybe 4. Abdominal bloating, weight loss 5. Immunosuppressed (esp steroids) are at risk of hyperinfection

iv. Dx: larvae (not eggs) in stool v. Tx: Ivermectin k. Trichinosis i. Eat muscle with larvae in them 1. Oft uncooked pork ii. Hatch in intestinepenetrate intestinemusclecysts iii. Clincial: fever, severe muscle aches, periorbital edema, heliotrope rash 1. If severe, myocarditis iv. Tx: Unnecessary. Albendazole can kill worms, but theyll die on their own anyway l. Filariasis i. Pathophys 1. Infected mosquito bites 2. Travels to lymph nodes a. Grow long- block lymph nodes 3. On ultrasound, can be seen flailing around 4. Can live in blood a. Only come out at night ii. Disease: edema, Hydrocele, elephantiasis iii. Dx: look in blood at night OR antigen test iv. Tx: Albendazole + Ivermectin m. River-Blindness Onchocerciasis i. South Africa, Yemen ii. Transmission: Black fly (breeds in rapid streams) iii. Live in subQ nodules (oft on the head) iv. Inflammitory response causes blindness v. Can also cause skin changes/inflammation in skin 1. leopard skin vi. Dx: microfilariae in blood vessels vii. Tx: Ivermectin 1. Blocks neurotransmission in worms 2. Clears it from skin and eyes, safely 3. But only temporarily. Spares adult worms. 4. So kill the blackflies 5. Other: a. There is a bacterium IN the worm: Wolbachia i. Kill thatkills O. Volvulus ii. Doxy n. Schistosomiasis i. A fluke (trematode) ii. Liver disease due to inflammatory response to eggs iii. Pathophysiology 1. Intermediate host: snail

2. Forms circariae (w fork-like tails) a. Can penetrate human skin 3. Entersdifferentiates into adultmigrates to specific tissue a. If it enters the wrong host, it dies i. Swimmers itch is from Avian Schistosomiasis iv. S. Mansoni 1. Eggs have a lateral spine 2. Goes to myenteric plexus, Portal circulation a. Causes portal hypertension i. pipe stem fibrosis ii. Caput medusa, esophageal varices, etc b. Granulomas surrounding eggs c. In intestine, each egg causes a polyp i. Can bleed 3. Can lead to malnutritionpoor development, low IQ 4. Can help with allergies. 5. Tx: not much. Kill the snails a. Drugs help expose more s. mansoni antigens to the immune system b. Praziquantel v. S. Hematobium 1. Eggs have a terminal spine 2. Only in Africa (esp sub-Saharan) 3. This one goes to the BLADDER PLEXUS a. Can cause fibrotic, dilated ureters, fibrotic bladderrenal failuredeath b. Can also get them on the cervixprone to bleeding i. More susceptible to other infections like HIV o. Paragonimus infection i. Pathophys 1. Ingest raw crayfish 2. Hatch in intestinemigrate to lungscoughswalloweggs in feces p. Tapeworms i. Have scolexes, proglottids ii. Cysticercosis 1. Clinical: a. Headache, focal deficits, new onset seizures 2. Pathophys a. Ingest cystercerci in tissues of undercooked meat i. Usu pork b. Larva attaches to intestineadultreleases eggs i. This is asymptomatic c. Ingest eggs

i. Larvae can travel to 1. Brain: Cerebral cysticercosis 2. Muscle/soft tissue: calcify, seen on Xray 3. Dx: CT/MRI, CSF serology 4. Tx: not always necessary. a. Albendazole w/ dexamethacin b. Surgery iii. Diphyllobothrium Latum (Fish tapeworm) 1. Eating undercooked freshwater fish 2. Can be 10 meters long 3. Clinical a. Anemia, B12 deficiency 4. Tx: Niclosamide 23. STDs II (cervicitis, urethritis, vaginitis, etc) a. Urethritis/cervicitis i. Urethritis: Discharge, disuria, PMNs 1. If gram negative Diplococci seengonorrhea 2. If notNGU ii. Cervicitis: Cervical mucopurulent discharge, cervical friability 1. Gram stain isnt as specific iii. Gonorrhea 1. Caused by Neisseria Gonorrhoeae a. Gram negative nonmotile Diplococcus b. INSIDE the PMN c. Oxidase positive d. Likes CO2 environment 2. Has pili with antigenic variation 3. Outer membrane proteins help it invade cells 4. Pathogenesis a. Mucosal contact necessary b. Incubation 7 days (closer to 3-4) c. Pili attachendocytosisinflammatory responsepus (yellowgreen) d. Naturally clear it in 1-2 mo i. But can get scarring, infertility from it 5. Clinical a. Urethritis- can lead to epididimitis b. Cervicitis- can lead to PID, perihepatitis (w normal LFTs) c. Disseminated- can be serious. Dermatitis (nodules) d. Conjunctivitis e. Pharyngitis 6. Tx: cephtriaxone

a. Can co-treat for Chlamydia (azythromycin) iv. Chlamydia 1. Obligate intracellular 2. Infectious particle is the elementary body a. Invades cell, prevents fusion with lysosome 3. Clinical a. NGU i. Discharge is white or clear, more mucoid ii. Can progress to epididimitis b. Mucopurulent Cervicitis- can become salphingitis i. Discharge is less purulent c. Lymphadenitis venerum i. Matted inguinal lymph nodes ii. Groove sign 4. Tx: single dose azythromycin b. Vaginitis, vaginosis syndromes i. Copious vaginal discharge ii. Normal vaginal flora: lactobacillus 1. Keeps pH low 2. Protects against pathogens, keeps other normal flora in check 3. Loss of lactobacillusincreased infection, other bacterial overgrowth iii. Vaginitis: 1. Inflammatory response (irritated vagina) 2. WBCs present iv. Vaginosis: 1. Decreased lactobacillus, increased anaerobes 2. WBCs absent 3. Non-inflammatory v. Include 1. Bacterial vaginosis a. Thin discharge i. Adherent, greyish b. Elevated pH c. Fish-like odor with KOH d. clue cells i. Epithelial cells with ragged borders e. Tx: metronidazole (flagil) 2. Trichomaniasis a. Trichomaniasis Vaginalis i. Motile, seen on wet mount b. Frothy vaginal discharge (profuse) c. Itching

d. Elevated pH e. Cervical petechiae f. Men have no sx i. Treat the partner g. Tx: metronidazole (flagyl) 3. Vulvovaginal candidiasis a. yeast infection from candida b. Pseudohyphae/budding yeast on wet mount c. Thick white cottage cheese discharge d. Itching e. Low pH f. Tx: OTC stuff c. Exophytic syndromes i. HPV 1. 6 and 11 cause warts a. Rough, cauliflower appearance 2. 16 and 18 cause cervical dysplasia 3. Vaccine 4. Tx: ablate the warts a. This doesnt cure the virus ii. Molluscum contagiosum 1. Common pox virus in kids (not necessarily sexual) 2. Smooth domed lesions 3. Dx: visual 4. Tx: ablate the warts d. Ectoparasitic infections i. Pubic lice 1. Can see lice, eggs on hairs with naked eye 2. Tx: anti-lice shampoos a. Treat spouse, house too ii. Scabies 1. See the burrows 2. Can look like eczema e. Systemic STDs i. Pelvic Inflammatory Disease 1. See disease outside genital tract 2. Manifestations of a. Chlamydia, gonorrhea, anaerobes ii. Hep B 1. Vaccine-preventible 2. Blood-borne iii. HIV

24. HIV pathogeneiss a. Doublestranded RNA virus b. 2 kinds of tropism i. Human coreceptors necessary to gain entry into cell ii. CCR5 1. Early infection 2. Most of whats transmitted iii. CCXR4 1. Late infection c. Transmission i. Directly into bloodstream 1. Needles 2. Blood transfusion ii. Mucus membranes 1. Sex iii. Vertical transmission 1. In utero (uncommon); during delivery (MOST); breastfeeding d. Natural history i. First infected 1. Flu-like symptoms a. Ppl may think they have mono 2. Viral load very high a. Your body doesnt know how to fight it 3. Very infectious 4. MANY CD4 cells destroyed ii. Immune response (quiescent phase) 1. Steady state equilibrium, immune system fights back 2. HIV antibody level stable 3. Steadily losing CD4 cells 4. High level of inflammation 5. Few symptoms e. Dx: ELISA or rapid HIV test (fingerstick)positive, then western blot to confirm i. To diagnose acute HIV 1. HIV RNA test in plasma f. Always test HIV resistance i. Dynamic genome g. Tx: Anti-Retroviral Therapy i. When they have: 1. An AIDS defining illness (regardless of CD4) 2. CD4 LESS than 500 or 350 3. Nephropathy 4. Pregnancy

ii. 3 drugs of 2 classes (at least) h. Drugs: i. Reverse transcriptase inhibitors 1. Nucleoside a. Compete with natural nucleosides for inclusion into DNA 2. Non-nucleoside a. Bind to reverse transcriptasechange binding site ii. Protease inhibitors 1. Causes protease to lock, preventing cleavage iii. Fusion inhibitor iv. CCR5 receptor blocker v. Blocking integration i. Pregnancy: all should be on HAART. AZT j. Chronic effects of HIV i. Metabolic complications 1. Lipodystrophy a. Loss of fat in limbs, face b. Central obesity. Buffalo hump ii. Ostopenia iii. Increased CV risk iv. Increased malignancies v. Coinfection with hepatitis k. Prognosis is improving 25. HIV epidemiology, clinical manifestations a. Subsaharan Africa b. Lots of new infections in youth c. Those unaware of infection are most likely to spread d. Presentations i. Wasting syndrome 1. Uncommon now 2. Depletion of both fat and lean tissues ii. Oral Candidiasis 1. Very common 2. NOT an AIDS defining illness a. Esophageal candidiasis is i. Cobblestone-looking lesions 3. Pseudomembranous 4. Treat actutely, do not prophylax iii. Oral Hairy Leukoplakia 1. Non-movable white plaques on margins of tongue 2. EBV related 3. Oft shows up in non-symptomatic HIV

4. Doesnt require treatment iv. Cutaneous manifestations 1. Syphilitic chancre a. Higher syphilis rates b. More lesions c. More 2ndary, 3iary syphilis d. Tx: aggressively. e. Do an LP if severe or neuro manifestations 2. Bartonella henselae a. Looks like kaposis sarcoma b. Fever, night sweats, anemia c. Liver, spleen d. Treat with Doxy 3. Varicella Zoster a. Comes out as imm system wanes b. Tx acyclovir to avoid post-herpetic neuraligia 4. HPV a. Warts (disfiguring), cancer (increased dysplasia rates) are both concerns 5. Molluscum contagiosum a. Smooth, umbilicated lesions b. Sign of advanced disease c. Groin, face 6. Seborrheic dermatitis a. Nasolabial folds, eyebrows, back, chest, scalp b. Responsive to antifungals 7. Psoriasis a. Not more likely to get it, but if they have it, its SEVERE 8. Kaposis Sarcoma a. Heaped up vascular lesions i. Arms, gingival, anywhere b. HHV8 i. Reactivates causing malignancies in mucosal surfaces ii. Rarely becomes pulmonaryvery bad iii. Treat localized lesions 1. Cryotherapy etc 2. Systemic HCG- trial. Pregnancy helps. Weird v. Pulmonary syndromes 1. Community acquired pneumonia a. Much higher risk i. Young person w 2 CAPHIV test 2. Pneumococcal pneumonia

a. Most common cause of pneumonia in HIV b. Focal usually, diffuse if advanced c. HIV+ ppl get a vaccine 3. Pneumococcus Jiroveci (PCP) a. Most common AIDS defining opportunistic infction b. First: hilar infiltrates i. Hydrate 1. Then diffuse interstitial infiltrates c. Progressive exertional dyspnea d. Subacute e. Hypoxic f. Dx: induced sputum demonstrating organism g. Tx: high dose bactrim i. Side effects are bad. Dont give this unless its proven h. Prophylax with low dose bactrim 4. TB a. Oft atypical presentation b. Put them on isolation til youve ruled it out vi. Disseminated infections 1. Tuberculosis 2. Histoplasmosis a. Diffuse pulmonary infiltrates b. Non-necrotizing granulomas c. Bone marrow infiltration d. Dx: urine antigen test 3. Mycobacterium Avium Complex a. Advanced immunosuppression b. Inhale itdissemination c. Fever, night sweats, fatigue, weight loss, anorexia d. Granulomatous infiltration of liver, bone marrow 4. Lymphoma vii. Ocular 1. CMV Retinitis a. ketchup on eggs lesions i. White plaques on retina, hemorrhages on top b. May or may not have visual complaints viii. CNS manifestations 1. Guillan Barre a. Happens early 2. Chronic meningitis a. Somewhat later 3. Late disease:

a. HIV Dementia b. HIV neuropathy i. Similar to DM c. Toxo d. Cryptococcus i. Meningitis 1. Sometimes just cryptococcemia ii. CSF: High opening pressure, High protein, low glucose iii. Dx: antigen test e. CNS Lymphoma i. Ring enhancing lesions ii. Neuro findings, seizures f. Toxoplasma Gondi Encephalitis i. Protozoan reactivation 1. Reactivation of latent cysts ii. MULTIPLE Ring enhancing lesions iii. Dx: CSF PCR iv. Also causes ocular manifestations v. Tx: Pyrimethamine, sulfadiazine vi. Prophylaxis: TMP-SMZ g. Progressive Multifocal Leukoencephalopathy i. JC virus ii. Deep white matter lesions iii. No mass effect iv. No Tx. HAART helps (immune reconstitution) 26. Protozoans a. Can multiply in humans b. Not assosciated with eosinophilia c. Malaria i. Fever, Malaise, headache, anemia ii. Normal WBC, decreased platelets iii. Splenomegaly iv. Plasmodium Falciparum 1. Most severe infections a. Can infect RBCs of all ages i. Higher parasitic load b. Can lead to sequestration i. Ischemic events ii. Microvascular damage 2. Extracellular banana-shaped gametocytes 3. Ring forms 4. Maternal immunity protects infants

5. Young children are most severe 6. Quotidian fever 7. Malarial CNS infections- VERY SEVERE a. Dystonus v. Plasmodium Vivax 1. Less severe disease a. Infects YOUNG RBCs 2. Requires duffy antigen 3. Hypnozoites in liver a. Allow for relapse months/years later 4. Tertan fever vi. Plasmodium Ovale 1. Less severe disease a. Attacks IMMATURE RBCs 2. Mostly in Africa 3. Doesnt require Duffy vii. Dx: Thick and Thin smear viii. Tx: Uncomplicated 1. Oral combination therapy a. Quinine/doxy b. Mefloquin c. Malarone d. If Vivax or Ovale, i. Primaquine-eradicate hepatic hypnozoites ii. Check for G6PD first ix. Prophylaxis 1. Chloroquine- doesnt work against Falciparum (resistance) 2. Doxy- daily. Photosensitivity 3. Mefloquin- weekly. Psychosis 4. Malarone- weekly. Expensive. x. Pregnant 1. Dont go 2. Dont take Doxy. Take mefloquine, maybe d. Tripanomiasis (Chagas disease) i. Life cycle: 1. Transmitted by kissing bug. Bites you at nightdefecates on skinunconscious scratchinginoculation 2. Trypamastigotes travel to cardiac myocytesamastigotes a. Can go back into bloodtrypamastigotesget sucked out of blood by kissing bug again ii. Mostly south America iii. Acute Chagas:

1. Painless swelling of inoculation site. Romanas sign. Fever, malaise 2. Self-limited iv. Chronic 1. Continued infestation in cardiac myocites 2. Dilated cardiomypopathy, conduction blocks 3. Mega-esophagus, megacolon (rarer) v. Dx: 2 out of 3 independent serological tests vi. Tx: actually does help 1. Benznidazole 2. Nefurtomox vii. HIV- can get it really bad. Can be Fatal. e. Leishmaniasis i. In the us, Military personnel from Iraq etc ii. Life cycle 1. Sandfly bites a. Promastigotes enter b. Enter cells c. Become amastigotes d. Replicates in cells iii. Cutaneous 1. Most common form 2. Lesion happens weeks after infection a. Starts out looking like a pimple b. Ulcerates w raised border 3. Heals in months, leaving a scar iv. Mucocutaneous 1. Braziliensis 2. Occur years after initial cutaneous infection 3. Occur on any mucosal surface (usu nose, mouth, pharynx) 4. Very disfiguring 5. Difficult to treat 6. Can be fatal v. Visceral (Kala Azar) 1. India, Africa, brazil 2. L. Dovani, L. infantum 3. Subacute: fever, weightloss a. Hepatomegaly, splenomegaly b. Can infect bone. c. (Liver, spleen, bone) 4. Hyperpigmentation (black fever) 5. Die from secondary infection 6. Dx: splenic needle aspirate

vi. Tx: Pentavalent antomonials 1. Amphotericin B f. Toxoplama Gondii i. Intracellular parasite ii. Cat is definitive host 1. Cat feces (can be on unwashed vegitables) 2. Can infect fetus 3. Can infect other animals iii. Acute: usu asx 1. Mono-like 2. Generalized lymphadenopathy iv. Congenital 1. Worse in later trimesters 2. Hydrocephalus 3. Retinal choroiditisblindness v. Transplants (donor positive, recipient negative) vi. HIV: Severe disease 1. Necrotizing brain lesions 2. Represent reactivation 3. Pyramethamine, sulfadiazine g. E. Histolytica i. Bloody diarrhea ii. Oft travelers to endemic areas (like Mexico) iii. Ingest cysts 1. become trophozoites in intestine a. become more cysts, exit, OR b. invasion: liver, heart lungs iv. Diagnosis by serology (looking at cysts in stool doesnt help) v. Flask shaped ulcer in mucosa vi. Clinical: 1. Amoebic Dysentery a. Bloody, small volume stools b. Tx: metronidazole (to kill trophozooites) AND i. tromomidacin (to eradicate cysts) 2. Amoebic Liver Abscess a. anchovy paste as you drain it b. May be fatal c. Biopsy to prove its not neoplasm h. Giardia i. Children in daycare, Campers, hikers ii. Feces, water contaminated with feces iii. Secretory diarrhea, flatulence

iv. 60% asymptomatic v. 30% self-limited diarrhea vi. 10% chronic diarrhea vii. Dx: stool microscopy viii. Tx: metronidazole i. Cryptosporidiosis i. Community swimming pools ii. Animal reservoirs transmit disease iii. Intracellular iv. Intestinal parasite 1. Forms cysts 2. Resist chlorination v. Immunocompetent- self-limited watery diarrhea vi. Immunocompromised- severe, cholera-like diarrhea j. Trichomoniasis i. Yellow vaginal discharge, itching. Can be bubbly ii. Strawberry cervix iii. Wet mount-motile pear shaped cells iv. Men are asxtreat them to prevent reinfection v. Tx: metronidazole 27. Bioterrorism and Zoonosis a. Features of a bioweapon i. High morbidity/mortality ii. Available iii. Dispersible b. Anthrax i. the perfect weapon ii. Gram positive bacillus 1. bamboo appearance iii. Aerobic, encapsulated. iv. Forms spores 1. Very hardy 2. Can survive in nature for decades 3. Become active when in the respiratory tract 4. Shit. v. Produces toxins (doesnt invade tissue) 1. Edematoxins- causes influx of fluids 2. Lethal toxin- creates massive cytokine response vi. Disease forms: 1. Cutaneous: a. Spore lands on damaged skin b. Most common, low fatality

c. Painless papuleedema (from edematoxin) black ulcervery black escharheals without scar 2. Gastrointestinal a. Ate an infected animal b. Aerosolized form got into nasopharynxswallowed c. Mortality 50% 3. Inhalational a. Mortality up to 95% b. Incubation is usu around 7 days (can be up to 6 weeks) c. Prodromal phase: Influenza w/nausea and vomiting d. Flu improves, quickly becomes fulminant i. sepsis ii. Respiratory failure, shock iii. Death e. Dx: Blood culture. It grows quickly. f. Widened mediastinum on clear lungs i. Bacteria get into lungs ii. Macs engulf them iii. Go to mediastinal lymph nodes iv. Get hemorrhagic necrosis g. Tx: ciprofloxacin or doxycycline i. wont respond to CAP drugs 4. no person-to-person transmission c. Smallpox i. Incubation: 7-14 days ii. Person to person transmission iii. Rash marks infectiveness iv. Prodrome: 1. Sudden, severe, flu-like sx 2. 3-5 days long v. Rash: 1. Face, hands, feet worst (even palms and soles) 2. Stages: maculopapulardeeperpustulesdryscabscar 3. All the same age vi. Tx: none vii. Vaccine, prophylaxis work d. Plague (yersinia pestis) i. Zoonosis with flea vector ii. Only pneumonic form is person-to-person iii. Incubation 2-8 days iv. Lesion at site of inoculation v. Bubonic:

After bite, get enlarged painful lymph nodes a. May suppurate b. You may be very sick c. You may be septic d. You may die e. It may spread to the lungspneumonic plague vi. Pneumonic 1. Rapid onset pneumonia 2. Hemoptysis 3. Sputum culture shows gram negative rods a. Look like red safety pins 4. Tx: streptomycin, gentamycin vii. Septic- you get gangrene at the ends of your digits e. Tularemia i. Very very small gram negative bacillus ii. Intracellular iii. Mostly in MO, KS iv. rabbit fever v. Vector is fleas vi. Incubation 3-5 days vii. Fever w/o tachycardia viii. Ulcer at inoculation ix. Regional lymphadenopathy x. Pneumonic disease 1. Non-productive cough 2. Pleuritic chest pain xi. Dx: serology takes weeks, cultures are poorly sensitive. 1. Lab hazard. Warn them. xii. Tx: Streptomycin, Gentimycin f. Zoonoses i. Rabies 1. Bats, dogs 2. Pathogenesis a. Bite. Replication at site of inoculation i. Retrograde axonal spread ii. 10 cm/day iii. Goes to the brainstem/thalamus iv. Negri bodies 3. Prodrome: influenza-like a. Percussion myoedema, parasthesias 4. Non-mammals are no risk ii. Bartonellosis (cat scratch)

1.

iii.

iv.

v.

vi.

1. Gram negative intracellular bacillus 2. Febrile lymphadenitis 3. Mostly kids 4. Rarely severe 5. Dx: clinical, tissue PCR 6. Tx: Azythromycin Q fever 1. Coxiella burnetii 2. Cows, goats, sheep a. Direct contact b. Inhalational 3. Very contagious 4. Acute: a. Flulike sx b. Atypical pneumonia c. Tx: doxycycline 5. Chronic a. Endocarditis, osteomyelitis b. Tx: doxycycline and rifampin Brucellosis 1. Intracellular gram neg coccobacillus 2. Cows, goats, sheep 3. Direct contact, aerosol (placenta), unpasteurized cheese 4. Dx: serology 5. Fever, malaise, malodorous sweat, Sacroiliac joint involvement 6. Tx: doxycycline and aminoglycoside Leptospirosis 1. Gram negative helical bacteria 2. Triathalons 3. Dog, rodent urine 4. Self-limited 90% a. High fever, headache, conjunctival suffusion 5. Severe, biphasic 10% a. Weils disease b. Icterus, renal failure, hepatic failure 6. Dx: Serology 7. Tx: oral doxycycline a. Jarisch-Herxheimer reponse- you killed LOTS of cells at oncecytokine response Psittacosis 1. Chlamydia psitacci 2. From birds

a. Parrots spit on you! Erm 3. Aerosolized 4. Very infectious 5. Mono-like illness, fever, fatigue a. Consolidation in lower lobe 6. Dx: serology 7. Tx: doxycyline 28. HIV Negative Opportunistic Infections a. Infections caused by loss: i. Physical/mechanical barriers: staph, strep, pseudomonas, aspergillus, candida ii. Neutrophils: Extracellular bacteria (staph, strep, enterobacteraciae, pseudomonas), a. Candida, aspergillus iii. Complement: encapsulated extracellular bacteria 1. N. meningitides, s.pneumo iv. T cells: intracellular bacteria, viruses, broader spectrum of fungi 1. Nocardia, legionella, mycobacteria v. B cells: enteroviruses, giardia, s.pneumo, h.flu, n.meningitidis, s.aureus b. Immunosuppression i. Congenital ii. Acquired 1. Cancer chemotherapy- neutropenia, mucositis 2. Solid organ transplant- Cell mediated immunity 3. Bone Marrow Transplant all lost c. Cancer chemotherapy i. Neutropenia 1. Greatest risk of infection 2. Sudden dropworse 3. Longer durationworse 4. Empiric treatment is very important a. Pseudomonas, s.aureus b. Anaerobes (if a likely area) d. Solid Organ Transplant i. Specific organ transplanted matters 1. Greatest risk: lung, heart-lung transplants ii. Long or demanding surgeries more risk iii. Rejection of transplant more immunosuppressionmore risk iv. 1st month post transplant 1. Increased risk of NOSOCOMIAL infections a. Long hospital stay b. Immunosuppressed i. Candida, c. diff, catheter assosciated infections, etc 2. Organ specific infections

a. Ex: Kidney transplantUTI v. 1-6 Mo 1. T cell defects a. Viruses: CMV, herpesvirus b. Bacteria: TB c. Fungi: endemic mycoses, aspergillus d. Protozoans: toxoplasmosis vi. CMV 1. Most common in transplants 2. Highest risk with Donor Positive, Recipient Negative 3. Early onset (3-6 mo post transplant)- pneumonitis 4. Late onset (after that)- enteritis e. Bone marrow/stem cell transplant i. Autologous: minimal immune suppression ii. Allogeneic: 1. VERY immune suppressed 2. Long term 3. Stages a. Pre-engraftment i. Risks: 1. Neutropenia 2. Mucositis 3. Central venous catheter ii. Possible infections 1. Staph, strep, ecoli, klebsiella, pseudomonas 2. Aspergillus, candida 3. Give cefapime. Or Vanc (if MRSA) b. Early post-engraftment i. B and T cell defects ii. Risks 1. Lymphopenia 2. Hypogammaglobulinemia 3. Central venous catheter iii. Infections 1. Viruses (CMV, HSV, EBV, etc) 2. Bacteria (intracellular) 3. Fungi (many, including aspergillus) c. Late post engraftment i. Risks 1. Minimal GVHD 2. Chronic GVHD (organ failure, etc) ii. Infections

1. VZV 2. Encapsulated community pathogens a. Strep pneumo 4. CMV: risk if donor negative, recipient positive a. Nave immune system going into a CMV + body 5. Aspergillus: Biphasic a. First because of neutropenia b. Second because of B and T cell dysfunction i. Donor matching helps 29. Neonatal infections a. In utero infections i. TORCHES 1. Toxoplasmosis 2. Other (west nile virus, lymphangitic choriomenintitis, malaria) 3. Rubella 4. Cytomegalovirus-most common. Can lead to deafness 5. HIV, Hepatitis, HSV (but usually intrapartem) 6. Enteroviruses 7. Syphilis ii. Oh. And also, Chicken Pox, Lyme disease and Parvovirus b. Fever in a neonate: i. Bacterial 1. Order of frequency a. Group B Strep b. E. coli (tied) c. Other gram negs d. Strep Pneumo e. N. Meningitis 2. 67% are UTI 3. 2% are meningitis (dont miss this! LP all babies!) a. There are no signs of this 4. Most were gram negative 5. Most were ampicillin resistant a. Tx with ceftaxipime (3rd gen cephalosporin, gets into CSF) i. Plus ampicillin to cover Listeria ii. Viral (MOST LIKELY) 1. Varies with seasons iii. Group B Strep 1. Ascending infection. 2. Screen moms from 35-37 weeks 3. Low weight, premature, africanworse 4. Early onset (w/in 7 days of birth)

a. FAST onset. 6 hours of birth, theyre grunting and retracting b. Respiratory failure 5. Late onset (after 7 days) a. More insidious b. Bone, joint infections, bacteremia c. 50% will have meningitis iv. HSV 1. Baby presented as floppy, with hepatitis 2. Mom primary infection during pregnancy, lesions during deliveryworse 3. Most are HSV2 4. Skin, eye, mucus membrane disease 5. If treated with acyclovir good prognosis, no longterm sequelae 6. If untreatedbecomes disseminated. Often fatal. 7. CNS: Encelphalitis, fever, lethargy, seizures a. Most dont have rash 8. Disseminated: Liver, lung, brain, skin, adrenals a. Looks like bacterial sepsis b. Mortality 50-80% 9. Happens within first couple weeks of life v. Enterovirus 1. Coxsackievirus A, B, enterovirus 2. Peak in Summer, fall 3. Virus from moms blood crosses placenta, disseminates in baby 4. Hyper/hypothermia, poor feeding, irritability, flat, red rash 5. Dx: stool culture 6. Tx: ? 7. Prevention: handwashing vi. Hepatitis B virus 1. Neonates who get it at birth become chronic carriers a. Have a higher mortality 2. We vaccinate now 30. Osteomyelitis a. Difficult for antibiotics to get to the site b. Acute osteo: prior to formation of sequestrum (dead bone) c. Chronic osteo: after formation of sequestrum. Not duration dependent. i. Body puts out new bone (involucrum) d. Mechanism i. Bacteria causes inflammation 1. Inflammation squeezes vascular channelsischemianecrosissequestrum 2. inflammation strips the subperiosteum from boneperiosteal elevationstimulates new bone formation

ii. Sequestrum can extend out through skin and drain e. Adhesion plays crucial role i. S.aureus is most common bug ii. Anything that can make biofilms (coag neg staph) 1. Antibiotics cant penetrate them 2. Take out prosthesis. f. Classification i. Hematogenous 1. Kids a. Symptoms i. Pain on passive mvmt ii. Inability to move limb iii. May be warm iv. fever b. Staph aureus i. Brodies abscess 1. Drain it c. Long bones i. Capillary loop- stasis d. Neonates: can involve joint b/c of incompletely closed epiphysis 2. Vertebral in adults a. Sx: back pain, maybe neuro signs (BAD) b. Discitis and two adjacent vertebrae c. Usu in lumbar area, but can be anywhere d. Gram pos: from skin, soft tissue e. Gram neg: from urinary tract f. Can compress spinal chord i. So check for neurological signs. ii. This is a surgical emergency. 3. Development of sequestrum is slow. a. Acute osteo ii. Contiguous 1. Sx: a. May have a draining sinus b. Persistent pain c. Oft no fever 2. Trauma, surgery a. Usu staph aureus 3. Infected prosthesis, hardware a. Esp coag negative staph b. Sx: loosened implant 4. Biofilms

5. Rapid sequestral formation a. Chronic osteo iii. Vascular insufficiency 1. DM, neuropathy a. Oft start as foot ulcers b. Osteo will HURT though (finally) c. Avoid ill-fitting shoes 2. Usually chronic 3. Osteo if: a. Persistent ulcer or b. Bone is exposed/can be probed 4. Polymicrobial a. Staph aureus, gram negatives, anaerobes. iv. Other osteo 1. Sickle cell: salmonella a. Encapsulated bacteria (strep pneumo) i. b/c they have no spleen 2. Sneaker: pseudomonas 3. Endemic mycoses: Histo, blasto,coccidio, TB v. Dx 1. Xray (but takes 2 weeks to show signs on an Xray) 2. Bone scan (shows up faster, but shows any inflammation) 3. MRI- good but expensive 4. Bone Biopsy- gold standard a. Aerobic and anaerobic cultures b. dont bother culturing the sinus tract vi. Tx: 1. Acute: a. IV antibiotics for 4-6 weeks b. Switch over to oral faster in kids c. Surgery rarely necessary 2. Chronic a. Much more difficult b. Culture wont help. Need a bone biopsy to find organism c. Surgery to remove dead tissue d. IV antibiotics for at LEAST 6 weeks 31. Tic-borne Diseases a. Lyme Disease i. Borrelia burgdorferi 1. Spirochete 2. Multiple plasmids a. Some are linear (weird)

3. Natural reservoir: white-footed mouse ii. Vector: Ixodes scapularis 1. Mostly the nymph stage 2. Must be attached 24 hours to transmit a. B.burgdorferi multiplies in tick midgut b. Travels to saliva during the blood meal iii. Transvarial transmission: no iv. Geography: MN, WI, northern CA 1. Not around here. v. Early manifestations 1. Erythema migrans a. 6 cm in diameter, at the site of bite b. A week after the bite 2. Carditis, aseptic meningitis, bells palsy vi. Late manifestations 1. Arthritis- usu single knee a. Months after the bite 2. CNS- encephalitis a. Will have a positive blood test vii. Dx: Serology may not be helpful (not enough bug to make test positive) a. ELISA, Western Blot 2. Culture skin lesions, joint involved viii. Tx: Doxycycline b. Southern Tick Assosciated Rash Illness (STARI) i. Rash looks like Erythema Migrans ii. But its the lone star tick c. Rocky Mountain Spotted Fever i. Caused by Rickettsia 1. Small gram negative bacilli 2. Obligate intracellular 3. Replicate freely in cytoplasm ii. Assosciated with arthropods iii. Happens mostly in summer, mostly in kids iv. Geography: a belt across the central US v. Sx: 1. Incubation 2-14 days 2. Early: fever, headache, myalgia, abdominal pain 3. Rash: peripheral petechiae (nonblanching) a. Can be on palms and soles b. Petechiae are areas of intense vasculitis i. Can eventually cause shock vi. Tx: IMMEDIATE. Dont wait for tests.

1. Tick exposure + rash = treat, and get labs 2. Doxycycline, chloramphenicol d. Ehrlichiosis i. Human Monocytic Ehrlichiosis- involves the monocyte line 1. Caused by Ehrlichia chafeensis ii. Human Granulocytic Ehrlichiosis- involves neutrophils 1. Caused by Ehrlichia ewingii iii. Ehrlichia 1. Intracellular- lives in phagosomes a. Replicates (forms a morula) iv. Vectors: Lone star tick and I.scapularis (same as lyme disease) v. Common in 1. May, June 2. Middle aged, elderly vi. Sx: Fever, headache, myalgia 1. Rash in about 1/3 of pts 2. Low WBC, low platelets 3. Cytoplasmic inclusions in neutrophils 4. Severe: Meningitis, pneumonitis, hepatitis, disseminated intravascular coagulation vii. Dx: PCR viii. Tx: doxycycline 32. Risks to healthcareworkers a. N. Meningitidis i. The only form of meningitis that shows person-to-person transmission ii. Droplet transmission iii. Risk is small, but higher than in the general population iv. Risk: unprotected exposure to respiratory secretions 1. Cough, intubation, CPR v. Anyone with evidence of bacterial meningitisdroplet precautions vi. Post exposure prophylaxis 1. HCW with a high risk exposure before pt was on antibiotics 2. Household members 3. Roommates 4. Anyone who shared eating utensils 5. Day care classmates 6. Ciprofloxacin b. Tuberculosis i. Pt goes on airborne isolation ii. HCW post exposure assessment 1. TB skin test now, 2. TB skin test in 8-10 weeks

iii. No minimum infection time. Entering the room= exposure iv. High risk: pt is coughing, youre intubating, bronchoscopy, induced sputum c. Body Substance Exposures i. Happens mostly in residents in and house staff ii. Happens mostly in OR iii. Standard Precautions 1. Gowns, gloves, masks, eyewear 2. Wash hands after removing gloves 3. Do not put hand in front of contaminated sharp iv. Double gloving helps v. If exposed, call student/occupational health immediately vi. Consider 1. Type of exposure a. Needlestick is worst b. Fluid on intact skin is NO RISK. 2. Amount of fluid exposure 3. Infectious status of source a. Known blood borne infection b. Violent trauma c. IV drug use d. Homosexual practices, multiple partners 4. Your susceptibility a. Were you vaccinated for HBV? vii. Test the source 1. Hep B surface antigen 2. HCV antibody 3. HIV rapid test (less than 2 hours 4. If all are negativeyoure fine viii. Liklihood of transmission varies by pathogen 1. HBV = most likely to transmit 2. HCV next 3. HIV-least likely. Only by percutaneous, (maybe mucus membrane) ix. HBV 1. Vaccine preventable 2. After 3 doses of vaccine + documented immune reactionlifetime immunity. 3. No more followup 4. If not vaccinated, a. Start Hep B Immunoglobulin therapy b. Start the vaccination series 5. If we dont know your response, check ab levels a. If no response, give a booster

6. You dont need to rush your response. x. HCV 1. 2-3% of needlestick injuries get an acute infection a. Of those, 15-25% clear it spontaneously 2. Dont treat prophylactically/empirically. 3. Treat the acute illness a. Watch HCV RNA antibodies b. Watch LFTs xi. HIV 1. Very low transmission rates 2. If you get stuck, you wont get HIV. We have drugs for it. a. Take a deep breath. Dont panic i. Youre almost done with this outline ii. You wont get HIV from a needlestick iii. Puppies. 3. Seroconversion takes around 46 days i. W/in 6 mo 4. Get HCV, HIV togetheraffects seroconversion of both 5. If stuck a. IMMEDIATELY start post exposure prophylaxis b. Dont wait for test results c. 2 drugs for 28 days i. This takes risks down to almost nothing. 33. Approach to patient with fever a. Fever of 38.3 C (101 F) on several occasions b. More than 3 weeks c. No diagnosis despite workup i. Rule out: being an idiot d. Mostly unusual presentations of common diseases i. Infections (eg: TB, culture negative endocarditis) ii. Neoplasms (lymphoma, esp hodgekins, renal cell carcinoma) 1. Cytokine release, tissue necrosis, secondary infectionfever iii. Collagen Vascular disease 1. Older patients a. Temporal arteritis: vision changes, fever for a few weeks b. Polymyalgia rheumaticia 2. Middle age a. Polyarteritis Nodosa 3. Young a. Adult Stills Disease iv. Misc. causes 1. Granulomatous

a. Crohns, sarcoid, granulomatous hepatitis 2. Pulmonary Embolism 3. Drugs a. Seriously. All drugs do this. Why do we even bother? 4. Factitious fever a. Wow. Really? You put your thermometer in your coffee while I wasnt looking? b. TIME FOR THE RECTAL THERMOMETER! i. What? You feel better now? 5. Metabolic disorders a. Hyperthyroid e. Nosocomial FUO i. Same, but the patient is in the hospital ii. Gram negative, resistant bacteria iii. IV accessphlebitis iv. Bladder catheterUTI v. Intubatedpneumonia vi. NG tubesinusitis vii. Post operationsurgical site infection viii. On medicationdrug fever ix. On antibioticsC.Diff colitis x. Immobilizedrecurrent pulmonary emboli f. Immune Deficient FUO i. Neutropenic ppl oft get fevers ii. Cant make pus iii. Neutropenic + Fever = infection until proven otherwise 1. Treat them until you have reason not to. 2. Even if theyre stable 3. They wont have clinical signs iv. Gram negatives, pseudomonas, gram positives v. If something that covers that doesnt work, try antifungals g. HIV assosciated FUO i. TB ii. Histo iii. Crypto iv. MAC v. CMV vi. Lymphoma