Clinical Microbiology

Comprehensive study resource covering bacteriology, virology, mycology, parasitology, antimicrobial therapy, and laboratory diagnostics. Every organism, every drug, every stain you need to know.

1. Bacteriology

Gram Stain Culture Biochemical ID Pathogenesis Clinical Syndromes

Gram-Positive Cocci

Staphylococcus aureus - Catalase (+), Coagulase (+). Classic: skin abscesses, endocarditis (acute native valve), osteomyelitis, septic arthritis, pneumonia (post-viral), toxic shock syndrome (TSST-1), food poisoning (enterotoxins). MRSA: vancomycin, daptomycin, linezolid. MSSA: nafcillin, cefazolin. Key toxins: PVL (necrotizing pneumonia), TSST-1 (superantigen), enterotoxins A-E (emetic). S. epidermidis - Coagulase (-), novobiocin sensitive. Biofilm on prosthetics (catheters, joint replacements, heart valves). S. saprophyticus - Coagulase (-), novobiocin resistant. UTI in young sexually active women. Streptococcus pyogenes (GAS) - Bacitracin sensitive, PYR (+). Pharyngitis, scarlet fever (erythrogenic toxin), impetigo, cellulitis, necrotizing fasciitis, toxic shock-like syndrome. Post-streptococcal: rheumatic fever (M-protein mimicry), post-streptococcal GN. S. agalactiae (GBS) - CAMP (+), hippurate (+). Neonatal sepsis/meningitis (vertical transmission from colonized mother). Prophylaxis: intrapartum penicillin. S. pneumoniae - Optochin sensitive, bile soluble. Alpha-hemolytic, lancet-shaped diplococci. Most common cause of CAP, bacterial meningitis (adults), otitis media, sinusitis. Capsular polysaccharide vaccine (PCV15/20, PPSV23). Viridans group streptococci - Alpha-hemolytic, optochin resistant. S. sanguinis, S. mutans, S. mitis. Subacute bacterial endocarditis (damaged valves).

Gram-Positive Bacilli

Bacillus anthracis - Spore-forming, non-motile, box-car shaped. Cutaneous (eschar), inhalational (mediastinal widening), GI. Ciprofloxacin, doxycycline. Bacillus cereus - Motile. Emetic (fried rice, heat-stable toxin, 1-6h) and diarrheal (heat-labile, 8-16h) food poisoning. Clostridium perfringens - Double zone hemolysis. Gas gangrene (myonecrosis), food poisoning. Treatment: surgery + PCN + clindamycin. C. tetani - Tetanospasmin blocks RIM -> spastic paralysis, trismus, opisthotonos. Prevention: DTaP. Treatment: HTIG + metronidazole. C. botulinum - Blocks ACh at NMJ -> flaccid paralysis (descending, symmetric, bulbar). Infant (honey), foodborne, wound. Antitoxin. C. difficile - Toxin A + B. Pseudomembranous colitis after antibiotics. Diagnosis: stool toxin PCR. Treatment: vancomycin PO, fidaxomicin, FMT. Listeria monocytogenes - Facultative intracellular, tumbling motility. Neonatal, pregnant (flu-like), elderly/immunocompromised meningitis. Ampicillin + gentamicin. Corynebacterium diphtheriae - Exotoxin ADP-ribosylates EF-2 -> pseudomembrane, myocarditis, polyneuritis. Antitoxin + erythromycin. Nocardia - Partially acid-fast, filamentous. Pulmonary, brain, cutaneous. TMP-SMX first-line.

Gram-Negative Cocci

Neisseria meningitidis - Oxidase (+), maltose (+). Capsule serogroups A, B, C, W, Y. Meningitis (children/young adults), meningococcemia, Waterhouse-Friderichsen. Prevention: MenACWY, MenB vaccines. Rifampin/CTX prophylaxis for contacts. Treatment: ceftriaxone. N. gonorrhoeae - Oxidase (+), glucose only. Urethritis, cervicitis, PID, disseminated (dermatitis-arthritis), ophthalmia neonatorum. Increasing FQ resistance. Treatment: ceftriaxone IM + azithromycin. Moraxella catarrhalis - Oxidase (+), DNase (+). Otitis, sinusitis, COPD exacerbation. Beta-lactamase (+).

Gram-Negative Bacilli

Escherichia coli - Lactose (+), beta-glucuronidase (+). Most common UTI (UPEC), neonatal meningitis (K1 capsule), traveler's diarrhea (ETEC), HUS (STEC O157:H7, Shiga toxin). CRE emerging threat. Klebsiella pneumoniae - Capsule, mucoid, currant jelly sputum. ESBL/KPC carbapenemase. Proteus mirabilis - Swarming, urease (+), struvite stones. Salmonella enterica - Non-lactose, H2S (+). Typhi: enteric fever, rose spots, relative bradycardia. Non-typhi: gastroenteritis. Shigella - Non-lactose, non-motile. Shiga toxin -> dysentery. Low infective dose (10-100 organisms). Pseudomonas aeruginosa - Oxidase (+), grape odor. VAP, burn infection, CF, malignant otitis externa, ecthyma gangrenosum. Anti-pseudomonal BL + aminoglycoside. Campylobacter jejuni - Microaerophilic, oxidase (+), curved. Most common bacterial gastroenteritis. Associated with Guillain-Barre. Helicobacter pylori - Urease (+). Peptic ulcer, MALToma, gastric cancer. Triple therapy (PPI + clarithromycin + amoxicillin/metronidazole). Haemophilus influenzae - X+V factors. Hib: meningitis (children), epiglottitis (thumbprint), pneumonia. Non-typeable: otitis, sinusitis, COPD. Legionella pneumophila - CYE agar, silver stain. Legionnaires' (hyponatremia, confusion). Azithromycin, levofloxacin. Bordetella pertussis - Paroxysmal whooping cough. DTaP, Tdap. Azithromycin early. Brucella - Undulant fever, livestock. Doxy + rifampin. Bartonella henselae - Cat scratch disease (lymphadenitis). Bacillary angiomatosis (HIV). Azithromycin.

Acid-Fast and Spirochetes

Mycobacterium tuberculosis - AFB, slow-growing. Ghon complex (primary), apical cavitary (reactivation), miliary, Pott disease, TB meningitis. Diagnosis: IGRA/PPD, AFB smear + GeneXpert + culture (MGIT). Treatment: 2HRZE/4HR (RIPE). MDR: BPaL. LTBI: 4R, 3HP, 9H. M. leprae - Cannot culture. Tuberculoid vs lepromatous leprosy. Dapsone + rifampin + clofazimine. MAC - Disseminated in AIDS (CD4 < 50). Clarithromycin + ethambutol + rifabutin. Nocardia - Partial AFB. Actinomyces - Sulfur granules, not AFB. PCN. Treponema pallidum - Darkfield. Syphilis: primary (chancre), secondary (rash palms/soles, condyloma lata), tertiary (neurosyphilis, gumma, aortitis). Diagnosis: VDRL/RPR + FTA-ABS/TP-PA. Treatment: benzathine PCN G (early), IV PCN G (neurosyphilis). Borrelia burgdorferi - Ixodes. Lyme: erythema migrans, AV block, Bell palsy, arthritis. Doxycycline (early), ceftriaxone (CNS). Leptospira - Weil disease. Doxycycline.

Atypical Bacteria (No Cell Wall)

Mycoplasma pneumoniae - No cell wall, sterols in membrane. Walking pneumonia (dry cough, young adults). Cold agglutinins. Macrolide/doxycycline/FQ (NOT beta-lactams). Chlamydia trachomatis - Obligate intracellular. A-C: trachoma (blindness), D-K: urethritis/cervicitis/PID, L1-L3: LGV. NAAT test. Azithromycin/doxycycline. C. pneumoniae - Mild CAP. C. psittaci - Psittacosis (birds). Rickettsia rickettsii - RMSF: fever, headache, centripetal petechial rash (wrists/ankles). Doxycycline. R. prowazekii - Epidemic typhus (louse). Orientia tsutsugamushi - Scrub typhus. Coxiella burnetii - Q fever (livestock). Acute: flu-like, pneumonia, hepatitis (doughnut granuloma). Chronic: endocarditis. Doxycycline (acute), doxy + hydroxychloroquine (chronic). Ehrlichia/Anaplasma - Morulae in monocytes/neutrophils. Doxycycline.

High-Yield Pearls
  • Catalase (+) = Staph only. Coagulase (+) = S. aureus only.
  • Optochin S, bile S = S. pneumoniae. Bacitracin S = S. pyogenes. CAMP (+) = GBS. PYR (+) = GAS.
  • Listeria: tumbling motility at 25 degrees C (cold enrichment).
  • Oxidase (+): Neisseria, Pseudomonas, Campylobacter, Legionella, Vibrio, Pasteurella.
  • Lactose fermenters (pink on MacConkey): E. coli, Klebsiella, Enterobacter.
  • Pseudoappendicitis = Yersinia enterocolitica. Ecthyma gangrenosum = Pseudomonas.
Red Flags
  • Meningococcemia: petechiae + shock -> ceftriaxone + droplet + contacts prophylaxis.
  • Necrotizing fasciitis (GAS): pain out of proportion -> emergent surgical debridement.
  • C. diff fulminant: ileus, toxic megacolon -> vancomycin PO + IV metronidazole.
  • MRSA bacteremia: TEE to rule out endocarditis.
  • Neurosyphilis: treat with IV PCN (NOT benzathine - does not cross BBB).

2. Virology

DNA Viruses RNA Viruses Hepatitis HIV Prions Antivirals

DNA Viruses

All DNA viruses are dsDNA except Parvovirus (ssDNA). All replicate in nucleus except Poxvirus (cytoplasm). Mnemonic: "Papp-H" - Papilloma, Adeno, Polyoma, Parvo, Herpes, Hepadna, Pox. Herpesviridae (8 types): HSV-1 (oral, encephalitis - temporal lobe), HSV-2 (genital, neonatal). Latency in sensory ganglia. Acyclovir, valacyclovir. Acyclovir-R: foscarnet. VZV: Chickenpox, shingles. Varicella vaccine, Shingrix. EBV: Mononucleosis (fever, pharyngitis, LAD), hairy leukoplakia, PTLD, Burkitt, nasopharyngeal CA. Monospot (+), VCA IgM. CMV: Retinitis (CD4 < 50), pneumonitis, colitis, congenital (calcifications, SNHL). Ganciclovir. HHV-6: Roseola. HHV-8: Kaposi sarcoma. Adenovirus: Pharyngoconjunctival fever. HPV: 6/11 warts, 16/18 cancer. Gardasil 9. BK: Cystitis/nephropathy. JC: PML. Parvovirus B19: Fifth disease, aplastic crisis, hydrops. Pox: Molluscum, Mpox.

RNA Viruses (+) - "PET CALF"

Picorna: Polio (asymmetric flaccid paralysis), Coxsackie A (herpangina/HFMD), B (myocarditis/pleurodynia), rhinovirus, HAV. Corona: SARS-CoV-2. Toga: Rubella (congenital: cataracts, PDA, SNHL), Chikungunya. Calici: Norovirus. Astro: Gastroenteritis. Flavi: HCV, Yellow fever, Dengue (ADE), Zika (microcephaly, GBS), West Nile (encephalitis), JE. Retro: HIV, HTLV.

RNA Viruses (-) - "PaRAnormal"

All cytoplasm except Orthomyxo (nucleus). Paramyxo: Measles (Koplik, 3 Cs, SSPE), Mumps (parotitis, orchitis), RSV (bronchiolitis), Parainfluenza (croup). Rhabdo: Rabies (Negri bodies, hydrophobia). HRIG + vaccine PEP. Orthomyxo: Influenza A/B. Drift + shift. Oseltamivir, baloxavir. Filo: Ebola, Marburg. Arena: LCMV, Lassa. Bunya: Hantavirus (HPS), RVF, CCHF.

Hepatitis Viruses

HAV: Picorna, fecal-oral, self-limited. Vaccine. HBV: Hepadna, blood/fluids. Perinatal/sexual/IVDU. Serology: HBsAg (+) = infected, anti-HBs (+) = immune, anti-HBc IgM = acute. Entecavir, tenofovir. Vaccine. HCV: Flavi, blood/IVDU. Chronic 70-85% -> cirrhosis/HCC. DAA: sofosbuvir/velpatasvir 12wk (pan-genotypic). SVR > 95%. HDV: Defective, requires HBsAg. HEV: Fecal-oral. High mortality in pregnancy.

HIV and Prions

HIV: gp120 + CD4/CCR5 or CXCR4. RT, integrase, protease. Acute: mononucleosis-like. AIDS: CD4 < 200. OIs staged by CD4. ART: INSTI + 2 NRTIs. U=U. PrEP: TAF/FTC. PEP: 28d RAL + TDF/FTC. HTLV-1: Adult T-cell leukemia, HAM/TSP. Prions: PrPSc, no nucleic acid. CJD (rapid dementia, myoclonus, PSW EEG), vCJD, kuru. MRI cortical ribboning. No treatment.

High-Yield Pearls
  • DNA viruses: all nucleus except Pox (cytoplasm). RNA (-): all cytoplasm except Orthomyxo.
  • EBV infects B cells (CD21). HIV infects CD4+ T cells.
  • Hepatitis B serology: HBsAg (+) = infected; anti-HBs (+) = immune; anti-HBc IgM = acute.
  • HCV DAA: sofosbuvir/velpatasvir 12wk (all genotypes) or glecaprevir/pibrentasvir 8wk.
  • HSV encephalitis: temporal lobe -> empiric acyclovir.
  • Rabies: PEP with HRIG + vaccine ASAP - near 100% fatal if symptomatic.
Red Flags
  • Neonatal HSV: vesicles + seizures + DIC -> high-dose acyclovir.
  • HIV OI ppx: PCP if CD4 < 200, Toxo if CD4 < 100, MAC if CD4 < 50.
  • Congenital CMV: most common infectious SNHL cause.
  • Dengue hemorrhagic: secondary infection -> ADE -> careful fluid management.
  • PML (JC virus): demyelination in HIV -> ART immune reconstitution primary management.

3. Mycology

Yeasts Molds Dimorphic Superficial Systemic Opportunistic Antifungals

Superficial and Cutaneous Mycoses

Dermatophytes: Trichophyton, Microsporum, Epidermophyton. Infect keratinized tissue. Tinea capitis/corporis/pedis/cruris/unguium. KOH prep (hyaline septate hyphae). Topical terbinafine/clotrimazole; systemic terbinafine/griseofulvin/itraconazole. Malassezia furfur: Pityriasis versicolor (hypopigmented patches, trunk). "Spaghetti and meatballs" on KOH. Topical ketoconazole. Candida: C. albicans (most common), C. glabrata (fluconazole-R), C. krusei (intrinsic fluconazole-R), C. auris (MDR, emerging). Superficial: thrush, esophagitis, vulvovaginitis. KOH: pseudohyphae + budding yeast. Topical nystatin/clotrimazole; oral fluconazole.

Subcutaneous Mycoses

Sporothrix schenckii: Dimorphic. Lymphocutaneous sporotrichosis (rose thorn -> nodular ascending lymphangitis). Itraconazole. Chromoblastomycosis: Fonsecaea, Phialophora. Warty plaques. Itraconazole + cryosurgery. Mycetoma (eumycetoma): Madurella. Draining sinuses + grains. Itraconazole + surgery.

Systemic Dimorphic Fungi

Mold at 25 degrees C (soil), yeast at 37 degrees C (tissue). "Mold in cold, yeast in heat." Histoplasma capsulatum: Ohio/Mississippi valleys. Bat/bird droppings. Tiny yeast within macrophages. Acute/chronic/disseminated pulmonary, mediastinal fibrosis. Urine antigen. Itraconazole (mild), L-AmB (severe). Coccidioides immitis: SW US (Valley fever). Arthroconidia. Spherules with endospores. Erythema nodosum. Fluconazole (mild), L-AmB (severe). Meningitis: lifelong fluconazole. Blastomyces dermatitidis: Ohio/Mississippi, Great Lakes. Broad-based budding yeast. Pulmonary, skin, bone. Itraconazole, L-AmB for severe. Paracoccidioides brasiliensis: Latin America. Pilot wheel yeast. Talaromyces marneffei: SE Asia. HIV-associated (CD4 < 100). Molluscum-like lesions.

Opportunistic Systemic Mycoses

Aspergillus fumigatus: Septate hyphae, 45 degrees branching. ABPA (asthma/CF, IgE, central bronchiectasis), aspergilloma (fungus ball), invasive pulmonary (neutropenic, angioinvasive -> thrombosis). Galactomannan antigen. CT: halo sign, air crescent. Voriconazole first-line. Mucorales (Rhizopus, Mucor): Broad, non-septate, 90 degrees branching. Rhinocerebral (DKA), pulmonary. L-AmB + surgical debridement. Pneumocystis jirovecii: Cystic form, previously protozoan. PCP: dyspnea, dry cough, bilateral interstitial infiltrates, hypoxemia. CD4 < 200. Silver stain (cysts). Beta-D-glucan elevated. TMP-SMX + steroids (PaO2 < 70). Prophylaxis: TMP-SMX when CD4 < 200. Candida (deep): Candidemia, intra-abdominal, hepatosplenic. Echinocandin first-line. Cryptococcus neoformans: Polysaccharide capsule. Meningitis in HIV (CD4 < 100). India ink (negative stain), CrAg antigen. L-AmB + flucytosine induction, then fluconazole. C. gattii: Pacific NW, immunocompetent, cryptococcoma.

High-Yield Pearls
  • Dimorphic fungi: mold at 25 degrees C, yeast at 37 degrees C. "Mold in cold, yeast in heat."
  • Histoplasma: tiny yeast in macrophages. Coccidioides: spherules. Blastomyces: broad-based budding.
  • Cryptococcus: India ink, CrAg. L-AmB + flucytosine induction.
  • Aspergillus: 45 degrees, voriconazole. Mucor: 90 degrees, L-AmB + surgery.
  • PCP: TMP-SMX + steroids if PaO2 < 70. Prophylaxis CD4 < 200.
  • C. auris: MDR, hard to ID, ICU outbreaks.
Red Flags
  • Mucormycosis (rhinocerebral): black eschar, DKA -> emergent L-AmB + debridement.
  • Aspergillus angioinvasion: hemoptysis -> embolization/surgery.
  • Cryptococcal meningitis: high ICP -> serial LP, VP shunt if refractory.
  • Histoplasma mediastinal fibrosis: SVC/bronchial obstruction.
  • Coccidioidal meningitis: lifelong fluconazole.

4. Parasitology

Protozoa Nematodes Cestodes Trematodes Ectoparasites Antiparasitics

Blood and Tissue Protozoa

Plasmodium: P. falciparum (severe, cerebral, high parasitemia), P. vivax/ovale (hypnozoites -> relapse, primaquine needed), P. malariae (nephrotic), P. knowlesi (zoonotic, SE Asia). Vector: Anopheles. Thin/thick smear, RDT. ACT (artemether-lumefantrine) for uncomplicated falciparum. IV artesunate for severe. Chloroquine + primaquine for vivax/ovale (check G6PD). Babesia microti: Ixodes tick. Hemolytic anemia. Maltese cross (tetrad). Clindamycin + quinine. Toxoplasma gondii: Cats (oocysts). Congenital: chorioretinitis, hydrocephalus, calcifications. HIV (CD4 < 100): ring-enhancing brain lesions, single/multiple. Pyrimethamine + sulfadiazine + leucovorin. Trypanosoma cruzi: Reduviid bug. Chagas: Romaña sign, dilated cardiomyopathy (apical aneurysm), megaesophagus, megacolon. Benznidazole. T. brucei: Tsetse fly. African sleeping sickness: hemolymphatic -> CNS (somnolence). Suramin/pentamidine (early), melarsoprol/eflornithine (late). Leishmania: Sandfly. Visceral (kala-azar: fever, splenomegaly, pancytopenia), cutaneous (ulcers), mucocutaneous (espundia). L-AmB, miltefosine.

Intestinal and GU Protozoa

Giardia lamblia: Pear-shaped, 2 nuclei, ventral sucking disk. Foul-smelling fatty stool, bloating. Metronidazole or tinidazole. Entamoeba histolytica: Trophozoites with ingested RBCs. Dysentery, liver abscess ("anchovy paste"). Metronidazole + paromomycin. Cryptosporidium parvum: Acid-fast oocysts. Profuse watery diarrhea in HIV. Nitazoxanide. Cyclospora/Cystoisospora: Acid-fast. TMP-SMX. Trichomonas vaginalis: Motile, 5 flagella. Frothy yellow discharge, strawberry cervix. Metronidazole/tinidazole (both partners).

Helminths - Nematodes

Enterobius vermicularis: Pinworm. Perianal pruritus (nocturnal). Scotch tape test. Albendazole. Ascaris lumbricoides: Loeffler syndrome, obstruction. Hookworm: Ground itch, iron deficiency anemia. Albendazole + iron. Strongyloides stercoralis: Autoinfection. Larva currens. Hyperinfection with steroids/immunosuppression -> gram-negative sepsis (high mortality). Ivermectin first-line. Check serology before steroids in endemic areas. Trichinella spiralis: Pork. Periorbital edema, myalgia, eosinophilia. Albendazole + steroids. Wuchereria bancrofti: Lymphatic filariasis (elephantiasis). DEC + albendazole. Loa loa: African eye worm. Calabar swellings. DEC. Toxocara: Visceral larva migrans. Albendazole. Cutaneous larva migrans: Serpiginous tunnels. Albendazole/ivermectin.

Helminths - Cestodes and Trematodes

Cestodes: Taenia solium (pork, neurocysticercosis -> seizures, albendazole + praziquantel + steroids), T. saginata (beef, no cysticercosis), D. latum (fish, B12 deficiency), Echinococcus (hydatid cyst -> PAIR + albendazole). Praziquantel for most. Trematodes: Schistosoma (mansoni intestinal, haematobium bladder/hematuria/squamous cell CA, japonicum). Eggs with spines. Praziquantel. Clonorchis (cholangiocarcinoma). Fasciola (triclabendazole, NOT praziquantel). Paragonimus (lung fluke, hemoptysis).

Ectoparasites

Sarcoptes scabiei: Intense pruritus, burrows (web spaces, wrists). Permethrin 5% cream. Crusted scabies: permethrin + oral ivermectin. Pediculus humanus: Head/body/pubic lice. Permethrin. Body louse vectors typhus, trench fever, relapsing fever. Tunga penetrans: Sand flea. Demodex: Blepharitis, rosacea.

High-Yield Pearls
  • Malaria: P. falciparum = severe, cerebral, high parasitemia. ACT first-line. IV artesunate for severe.
  • Cerebral toxoplasmosis: multiple ring-enhancing lesions in HIV. Pyrimethamine + sulfadiazine.
  • Strongyloides: check serology before steroids. Ivermectin (NOT albendazole as first-line).
  • Neurocysticercosis: albendazole + praziquantel + steroids; seizure control.
  • Schistosoma haematobium: terminal spine eggs, hematuria, squamous cell bladder CA.
  • Scabies: permethrin 5% first-line. Treat close contacts.
Red Flags
  • Cerebral malaria: altered consciousness, seizures -> IV artesunate.
  • Strongyloides hyperinfection: gram-negative sepsis, high mortality (~70%). Ivermectin.
  • Hydatid cyst rupture: anaphylaxis -> PAIR with albendazole cover.
  • Visceral leishmaniasis: fever + splenomegaly + pancytopenia -> L-AmB.
  • Chagas cardiomyopathy: heart block, apical aneurysm, stroke -> benznidazole early.

5. Antimicrobial Therapy

Mechanisms Spectrum Resistance Empiric Regimens Stewardship

Cell Wall Inhibitors

Beta-Lactams: Penicillins (GP, spirochetes). Anti-staph (nafcillin). Aminopenicillins (ampicillin). Anti-pseudomonal (piperacillin). Beta-lactamase combos (pip-tazo, amox-clav). Cephalosporins: 1st (cefazolin, GP > GN), 2nd (cefuroxime, GP+GN+anaerobes), 3rd (ceftriaxone/cefotaxime GN > GP, ceftazidime anti-pseudomonal), 4th (cefepime GP+GN+Pseudomonas), 5th (ceftaroline MRSA). Carbapenems (meropenem, ertapenem, imipenem) - broadest. Aztreonam - GN only, safe in PCN allergy. Glycopeptides: Vancomycin (MRSA, C. diff PO). Lipopeptides: Daptomycin (MRSA, VRE - NOT for pneumonia, surfactant inactivates). Polymyxins: Colistin (last resort MDR GN). Nephro/neurotoxic.

Protein Synthesis Inhibitors

30S: Aminoglycosides (gentamicin, amikacin - GN, synergy with cell wall agents, concentration-dependent, once-daily, oto/nephrotoxic). Tetracyclines (doxycycline, tigecycline - atypicals, Rickettsia, acne, MRSA SSTI. Avoid in children < 8). 50S: Macrolides (azithromycin - atypicals, CAP, MAC. QTc). Chloramphenicol (aplastic anemia). Linezolid (MRSA, VRE - myelosuppression, serotonin syndrome). Clindamycin (GP anaerobes, toxin suppression - C. diff risk). Quinupristin/dalfopristin (VRE faecium).

Folate, DNA and RNA Synthesis Inhibitors

TMP-SMX: Broad (UTI, PCP, toxoplasmosis, MRSA SSTI, Nocardia, Stenotrophomonas). Sequential blockade of folate synthesis. Sulfa allergy, hyperkalemia. Fluoroquinolones: Cipro/levo (GN, Pseudomonas), moxifloxacin (anaerobes). DNA gyrase + topo IV inhibition. Tendinopathy, QTc, C. diff, neuropathy. Rifampin: RNA polymerase inhibitor. TB (RIPE), Staph biofilm, meningococcal ppx. CYP3A4 inducer. Metronidazole: Anaerobes (B. fragilis), protozoa (Giardia, E. histolytica, Trichomonas). Disulfiram-like with alcohol.

Antivirals, Antifungals and Antiparasitics

Anti-herpes: Acyclovir (HSV, VZV). Valacyclovir, famciclovir. Foscarnet (TK-independent). Anti-CMV: Ganciclovir, valganciclovir. Anti-influenza: Oseltamivir (NA inhibitor), baloxavir (cap-dependent endonuclease). Anti-COVID: Remdesivir, nirmatrelvir/ritonavir. Anti-HBV: Entecavir, tenofovir. Anti-HCV: DAA (sofosbuvir, velpatasvir). Anti-HIV: INSTI + NRTIs. Antifungals: Polyenes (Amphotericin B - ergosterol, nephrotoxicity). Azoles (fluconazole, voriconazole, isavuconazole - inhibit 14α-demethylase). Echinocandins (beta-glucan synthase - Candida first-line). Flucytosine (combination). Terbinafine (dermatophytes). Antiparasitics: ACT (malaria), metronidazole (protozoa), albendazole (nematodes), ivermectin (Strongyloides, filaria, scabies), praziquantel (cestodes, trematodes).

Resistance Mechanisms

Beta-lactamases: Penicillinase (S. aureus), ESBL (E. coli, Klebsiella - hydrolyze 3rd gen cephalosporins), AmpC (Enterobacter - inducible), Carbapenemases (KPC, NDM, OXA-48). MRSA: mecA -> PBP2a (low affinity). VRE: VanA/VanB -> D-Ala-D-Lac. MDR-TB: R + I resistance. XDR-TB: + FQ + injectable. Efflux, target modification, porin loss. Antibiotic stewardship: right drug, right dose, right duration. De-escalate based on cultures. Shorten: CAP 5d, HAP 7d, UTI 3-5d. PCT guidance.

Key Pearls
  • Vancomycin: trough 15-20 for serious. Red man = infusion rate (pre-treat).
  • Aminoglycosides: once-daily dosing, concentration-dependent. Monitor peak/trough.
  • Daptomycin: DO NOT use for pneumonia.
  • TMP-SMX: PCP prophylaxis/tx, MRSA SSTI, Nocardia.
  • Azoles all inhibit CYP450 (except fluconazole fewer interactions). Voriconazole: TDM.
  • Echinocandins: fungicidal vs Candida, not active vs Cryptococcus.
  • ESBL: treat with carbapenem, NOT cephalosporins (even if sensitive in vitro).
Red Flags
  • C. diff highest risk: clindamycin, FQ, cephalosporins.
  • Serotonin syndrome: linezolid + SSRI -> hyperthermia, clonus.
  • QTc prolongation: macrolides + FQ + azoles. Check EKG.
  • Aplastic anemia: chloramphenicol (1:30,000). Avoid unless no alternative.
  • Colistin nephrotoxicity: 30-50% of courses. Monitor Cr.

6. Lab Diagnostics

Stains Culture Media Biochemical Tests Serology Molecular AST

Stains and Microscopy

Gram Stain: CV -> iodine -> decolorizer -> safranin. GP = purple, GN = pink/red. Ziehl-Neelsen (AFB): Carbol fuchsin + heat -> acid-alcohol -> methylene blue. AFB = red. Kinyoun: Cold AFB. Modified AFB: Nocardia, Cryptosporidium. India Ink: Cryptococcus (capsule, negative stain). Silver (GMS): Fungi black, PCP cysts. Giemsa: Malaria (rings), Babesia (Maltese cross), Toxoplasma (tachyzoites), Chlamydia (inclusions). KOH: Fungal hyphae. Calcofluor White: Fluorescent fungal stain. Trichrome: Intestinal protozoa. Tzanck: Multinucleated giant cells (HSV/VZV). Darkfield: Spirochetes (Treponema).

Culture Media

Blood Agar: Hemolysis pattern (alpha/beta/gamma). Chocolate Agar: X+V factors (Neisseria, Haemophilus). MacConkey: Selective (GN) + differential (lactose = pink). EMB: Metallic sheen (E. coli). MSA: Selective (7.5% NaCl) + differential (mannitol = yellow for S. aureus). Thayer-Martin: VCNT (Neisseria selective). Lowenstein-Jensen: TB (egg-based, 2-8wk). MGIT: Mycobacteria liquid (1-3wk). Sabouraud Dextrose: Fungi (low pH). BCYE: Legionella (iron + cysteine). TCBS: Vibrio (yellow). CHROMagar: Candida species ID by color.

Biochemical Tests (Key Flowchart)

Catalase (+) -> Staph. Coagulase: S. aureus (+) vs others (-). Catalase (-) -> Strep. Hemolysis: α (pneumo: optochin S, bile S vs viridans: optochin R, bile R), β (GAS: bacitracin S, PYR + vs GBS: CAMP +, hippurate +), γ (Enterococcus). Lactose (+) MacConkey -> E. coli (indole +) vs Klebsiella/Enterobacter (indole -). Lactose (-) MacConkey -> H2S (+) Salmonella vs H2S (-) -> urease (+) Proteus vs urease (-) Shigella. Oxidase (+): Neisseria, Pseudomonas, Campylobacter, Legionella, Vibrio, Pasteurella. Urease (+): H. pylori, Proteus, Klebsiella, Yersinia. PYR (+): S. pyogenes, Enterococcus. CAMP (+): GBS. DNase (+): M. catarrhalis, S. aureus. Bile solubility (+): S. pneumoniae. MALDI-TOF: Mass spec ID in minutes.

Serology, Molecular and AST

Serology: ELISA (antigen or antibody), Western blot (confirmatory HIV, Lyme). NAAT: PCR, GeneXpert (TB + RIF resistance, MRSA, C. diff, HIV VL, COVID, CT/NG). RT-PCR for RNA viruses. Quantitative PCR: HIV, CMV, HBV, HCV viral loads. Genotyping: HIV resistance, HCV genotype, 16S rRNA, WGS. AST: Kirby-Bauer disc diffusion, broth microdilution (MIC), Etest. Automated: Vitek, MicroScan. Breakpoints per CLSI/EUCAST. D-test: Inducible clindamycin resistance (D-zone). ESBL confirmation (clavulanate synergy).

Key Pearls
  • MacConkey: pink = lactose fermenter (E. coli, Klebsiella). Colorless = non-fermenter (Salmonella, Shigella, Pseudomonas).
  • Chocolate = Neisseria, Haemophilus (X+V). Thayer-Martin = Neisseria selective (VCNT).
  • MSA: S. aureus = yellow, S. epidermidis = red/pink.
  • MALDI-TOF replaced most biochemical panels - ID in minutes.
  • GeneXpert: automated PCR, rapid TB + RIF resistance.
  • D-test positive: do NOT use clindamycin (clinical failure risk).

7. Cheatsheets and Mnemonics

Memory Aids Organism Tables Key Associations Quick Reference

Gram Stain Quick Reference
GP Cocci

Staph (catalase+), Strep (catalase-), Enterococcus

  • Coagulase (+) = S. aureus
  • Optochin S = pneumo
  • Bacitracin S = S. pyogenes
GP Bacilli

Bacillus, Clostridium (spores), Listeria (tumbling), Nocardia (partial AFB), Corynebacterium, Actinomyces (sulfur granules)

GN Cocci

Neisseria (meningitidis and gonorrhoeae), Moraxella catarrhalis. All oxidase (+).

GN Bacilli (Enterics)

Lactose (+): E. coli, Klebsiella, Enterobacter. Lactose (-): Salmonella, Shigella, Proteus, Yersinia, Pseudomonas (oxidase +).

GN Bacilli (Resp.)

H. influenzae (X+V), Legionella (CYE), Bordetella, Brucella, Pasteurella, Francisella.

Acid-Fast

TB, leprae, MAC, marinum, kansasii. Partial: Nocardia, Cryptosporidium, Cyclospora.

Virus Classification
DNA Viruses "Papp-H"

Papilloma, Adeno, Polyoma (BK/JC), Parvo (B19), Herpes (8 types), Hepadna (HBV), Pox (smallpox, molluscum, Mpox).

RNA (+) "PET CALF"

Picorna, Corona, Toga, Calici, Astro, Flavi, Retro.

RNA (-) "PaRAnormal"

Paramyxo, Rhabdo, Arena, Orthomyxo, Filo.

Replication Sites

DNA: all nucleus except Pox (cytoplasm). RNA (-): all cytoplasm except Orthomyxo (nucleus). RNA (+): all cytoplasm. Retro: nucleus (integration).

Encapsulated Bacteria - "Please SHiNE SKiS"
Please SHiNE SKiS

Pseudomonas, S. pneumoniae, H. influenzae, Neisseria, E. coli, Salmonella, Klebsiella, Strep (GBS). Capsule = antiphagocytic. Vaccines target capsule (PCV, MenACWY, Hib). Splenectomy -> OPSI risk.

Key Organism-Disease Associations
Meningitis (adults)

S. pneumo, N. meningitidis, Listeria ( > 50/immunocompromised)

Meningitis (neonates)

GBS, E. coli, Listeria

CAP

S. pneumo, H. flu, M. pneumo, C. pneumo, Legionella

Endocarditis

Acute: S. aureus. Subacute: viridans strep. Prosthetic: coag-neg Staph. HACEK.

Osteomyelitis

S. aureus (most). Vertebral: TB. Sickle cell: Salmonella. Diabetic foot: polymicrobial.

UTI

E. coli (80%), S. saprophyticus (young women), Proteus, Klebsiella

Food Poisoning

1-6h: S. aureus, B. cereus (emetic). 8-16h: C. perfringens. 12-72h: Salmonella, Campylobacter, Shigella, ETEC, Norovirus. > 3d: Giardia.

Neutropenic Fever

Cefepime or pip-tazo or meropenem + vancomycin

Special Stains and Media Quick Ref
Cryptococcus

India Ink (capsule)

Legionella

Silver stain, BCYE agar

PCP

GMS silver stain, immunofluorescence

TB

Ziehl-Neelsen (AFB), auramine-rhodamine

Chlamydia

Giemsa (inclusions), NAAT

Malaria

Giemsa (thick/thin), RDT

Fungi

KOH, calcofluor white, GMS, PAS

Spirochetes

Darkfield, Warthin-Starry silver

Nocardia

Modified AFB, Gram (beaded GPB)

Empiric Treatment Quick Picks
Meningitis

Vanco + Ceftriaxone + Acyclovir +/- Ampicillin (Listeria). Dexa before abx.

CAP

Outpt: amoxicillin or doxy. Inpt: beta-lactam + macrolide. ICU: + FQ.

UTI

Nitrofurantoin or TMP-SMX (uncomplicated). Ceftriaxone (pyelo).

Cellulitis

Cephalexin, clindamycin, TMP-SMX (MRSA concern).

Sepsis

Cefepime/pip-tazo + vancomycin +/- aminoglycoside.

C. diff

Vancomycin PO (mild-sev). Fidaxomicin (recurrent). FMT (multiple recur).

Antifungal Quick Pick
Candidemia

Echinocandin. Step-down fluconazole if sensitive.

Cryptococcal

L-AmB + flucytosine induction, fluconazole consolidation.

Aspergillus

Voriconazole. Salvage: L-AmB, isavuconazole.

Mucor

L-AmB + surgery + control DKA.

PCP

TMP-SMX + steroids if PaO2 < 70.

Dimorphic

Mild: itraconazole. Severe: L-AmB then azole.

Biochemical ID Flowchart
Catalase (+)

Coagulase (+) = S. aureus. (-) = S. epi/S. saprophyticus (novobiocin R).

Catalase (-) Strep

α: pneumo (optochin S, bile S) vs viridans (R). β: GAS (bacitracin S, PYR +) vs GBS (CAMP +). γ: Enterococcus (PYR +).

Lactose (+) MacConkey

Indole (+) E. coli. Indole (-) Klebsiella, Enterobacter.

Lactose (-) MacConkey

H2S (+) Salmonella. H2S (-) Urease (+) Proteus. Urease (-) Shigella, Pseudomonas.

Memory Aids
  • Penicillin allergy alternatives: CAP -> doxy + FQ. Meningitis -> moxifloxacin. Syphilis -> doxy or ceftriaxone. Endocarditis -> vancomycin.
  • Which need vancomycin? MRSA, C. diff PO, ampicillin-R Enterococcus, PCN-allergy GP infections.
  • D-tetrad for doxycycline: Rickettsia, Chlamydia, Brucella, Lyme, Ehrlichia, Anaplasma, Mycoplasma, Vibrio, Yersinia, MRSA SSTI.
  • Beta-lactamase producers "SHiN BEK": S. aureus, H. influenzae, N. gonorrhoeae, B. fragilis, E. coli, K. pneumoniae.
Exam Traps
  • Most common UTI in catheterized: E. coli (but Proteus/Providencia biofilm if long-term).
  • Most common pneumonia in COPD: H. influenzae (not S. pneumo).
  • Most common pneumonia in CF: Pseudomonas.
  • Most common septic arthritis in young sexually active: N. gonorrhoeae (not S. aureus).
  • Most common viral gastroenteritis in adults: Norovirus (not Rotavirus).
  • ESBL: treat with carbapenem, NOT cephalosporins (clinical failure even if sensitive in vitro).

8. Treatment Tables

First-Line and Alternative Regimens for Key Infections

Bacterial Infections
InfectionFirst-LineAlternativeDuration
CAP (outpatient)Amoxicillin or DoxycyclineMacrolide, FQ5d
CAP (inpatient)Beta-lactam + MacrolideFQ monotherapy5-7d
HAP/VAPAntipseudomonal BL + anti-MRSACarbapenem + vanco/linezolid7d
UTI (uncomplicated)Nitrofurantoin or TMP-SMXFosfomycin3-5d
PyelonephritisCeftriaxoneFQ, carbapenem if ESBL7-14d
Cellulitis (mild)CephalexinClindamycin, TMP-SMX5-7d
MRSA SSTITMP-SMX or DoxycyclineClindamycin, linezolid5-10d
Bacterial MeningitisVanco + Ceftriaxone + DexaMeropenem, moxifloxacin10-21d
Septic ArthritisVancomycin + CeftriaxoneDaptomycin, FQ3-4wk
Osteomyelitis (acute)Nafcillin/Cefazolin (MSSA), Vanco (MRSA)Daptomycin, linezolid4-6wk
C. diff (mild-mod)Vancomycin PO 125mg QIDFidaxomicin10d
C. diff (severe/fulm)Vanco PO + IV MetronidazoleTigecycline, FMT14d
Diverticulitis (mild)Amox-clav or TMP-SMX + MetroMoxifloxacin5-7d
Pelvic Inflammatory DzCeftriaxone + Doxy + MetroFQ + Metro14d
GonorrheaCeftriaxone 500mg IMGentamicin + azithromycinSingle dose
Syphilis (early)Benzathine PCN G 2.4M IM x1Doxycycline 14dSingle dose
Lyme (early)Doxycycline 100mg BIDAmoxicillin, cefuroxime10-14d
TB (active)RIPE (Rifampin, INH, PZA, EMB)Per resistance pattern6mo (2 + 4)
TB (latent)4R (rifampin 4mo)3HP, 9H4mo
Fungal and Viral Infections
InfectionFirst-LineAlternativeDuration
CandidemiaEchinocandin (micafungin)L-AmB, fluconazole (if sensitive)14d after clearance
Cryptococcal MeningitisL-AmB + FlucytosineFluconazole high-dose2wk + 8wk
Invasive AspergillosisVoriconazoleL-AmB, isavuconazole >= 12wk
MucormycosisL-AmB + SurgeryPosaconazole, isavuconazole >= 12wk
PCPTMP-SMX + Prednisone (if PaO2 < 70)Pentamidine, atovaquone14-21d
Oropharyngeal CandidiasisFluconazole 200mg x1 + 100 x7dNystatin, itraconazole7-14d
HIV (treatment-naive)DTG/TAF/FTC (Biktarvy)RAL + TDF/FTC, DRV/c + TAF/FTCLifelong
InfluenzaOseltamivir (start < 48h)Baloxavir, zanamivir5d
COVID-19 (high-risk)Nirmatrelvir/ritonavir (Paxlovid)Remdesivir 3d IV5d
HSV EncephalitisAcyclovir 10mg/kg IV q8hFoscarnet (if acyclovir-R)14-21d
HSV Genital (1st)Valacyclovir 1g BIDFamciclovir7-10d
VZV (Shingles)Valacyclovir 1g TIDAcyclovir, famciclovir7d
CMV Retinitis (HIV)Valganciclovir 900mg BIDGanciclovir IV, foscarnet14-21d
HBV (chronic)Entecavir or TAFPEG-IFN (selected)Long-term
HCV (all genotypes)Sofosbuvir/velpatasvir 12wkGlecaprevir/pibrentasvir 8wk8-12wk
Parasitic Infections
InfectionFirst-LineAlternativeDuration
Malaria (uncomplicated falciparum)ACT (artemether-lumefantrine)Atovaquone-proguanil, quinine + doxy3d
Malaria (severe)IV ArtesunateIV quinine + doxycycline >= 24h
P. vivax/ovale (radical)Chloroquine + Primaquine (G6PD!)ACT + primaquine14d
GiardiasisTinidazole 2g single doseMetronidazole 7d1-7d
Amebic Dysentery/AbscessTinidazole + ParomomycinMetronidazole + diloxanide10d
Toxoplasmosis (HIV)Pyrimethamine + Sulfadiazine + LeucovorinTMP-SMX, atovaquone >= 6wk
TrichomoniasisTinidazole 2g single doseMetronidazole 500mg BID 7d1-7d
Chagas DiseaseBenznidazoleNifurtimox60d
Leishmaniasis (visceral)L-AmBMiltefosineVariable
Ascariasis/EnterobiasisAlbendazole single doseMebendazole1-3d
StrongyloidiasisIvermectin 200 mcg/kg POAlbendazole1-2d
NeurocysticercosisAlbendazole + Praziquantel + SteroidsSurgery (hydrocephalus)14d
SchistosomiasisPraziquantel 40mg/kgOxamniquine (S. mansoni)1 day
ScabiesPermethrin 5% cream x2Ivermectin 200 mcg/kg PO x21-2wk apart
Prophylaxis Quick Reference
PCP (CD4 < 200)

TMP-SMX DS daily or 3x/wk

Toxoplasma (CD4 < 100)

TMP-SMX DS daily

MAC (CD4 < 50)

Azithromycin 1200mg weekly

Surgery Prophylaxis

Cefazolin <= 60min before incision

Meningococcal Contacts

Rifampin 600mg BID 2d or CTX 250mg IM

Endocarditis (dental)

Amoxicillin 2g PO 30-60min pre (high-risk only)

GBS (intrapartum)

PCN G 5M then 2.5M q4h

Rabies PEP

HRIG + vaccine days 0,3,7,14

HIV PEP

RAL + TDF/FTC x28d (within 72h)

Malaria (travel)

Atovaquone-proguanil daily or doxycycline

Treatment Pearls
  • Sepsis 1-hr bundle: cultures, lactate, broad abx, 30mL/kg crystalloid, vasopressors PRN.
  • C. diff: avoid antiperistaltics (toxic megacolon risk).
  • MRSA SSTI with I&D: antibiotics may not be needed if drained.
  • TB: check LFTs (INH hepatotoxic), give B6 with INH (prevents neuropathy).
  • Malaria: IV artesunate superior to IV quinine (lower mortality).
  • Influenza: antivirals benefit within 48h of onset.

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