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 & 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°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 & 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 & 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°C (soil), yeast at 37°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° 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° 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°C, yeast at 37°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°, voriconazole. Mucor: 90°, 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 & 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 & 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 & 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 & 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 & 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 & 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 & 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 & 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 & 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 & 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 & 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 & 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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