Microbiology
Bacteriology, virology, mycology, parasitology, antimicrobial mechanisms, resistance patterns, and every organism, virulence factor, diagnostic test, and treatment principle across the full scope of medical microbiology.
01 Overview & Scope of Medical Microbiology
Medical microbiology is the study of organisms that cause human disease — bacteria, viruses, fungi, and parasites — and the host responses they provoke. It is the scientific foundation of infectious disease medicine and underpins rational antimicrobial prescribing, infection prevention, and public health policy. Every clinical specialty encounters infectious diseases, making microbiology one of the most cross-cutting foundational sciences.
Why This Matters
Infectious diseases remain the leading cause of death worldwide. Understanding the organisms, their virulence mechanisms, diagnostic approaches, and treatment principles is essential for every physician regardless of specialty. Microbiology is heavily tested on USMLE Step 1 and Step 2 CK.
Major Categories of Human Pathogens
| Category | Characteristics | Size | Examples |
|---|---|---|---|
| Bacteria | Prokaryotic, peptidoglycan cell wall, binary fission | 0.5–5 µm | S. aureus, E. coli, M. tuberculosis |
| Viruses | Obligate intracellular, DNA or RNA genome, no ribosomes | 20–300 nm | HIV, influenza, SARS-CoV-2, HSV |
| Fungi | Eukaryotic, chitin cell wall, ergosterol membrane | 2–10 µm (yeast) | Candida, Aspergillus, Histoplasma |
| Parasites | Eukaryotic; protozoa (single-celled) and helminths (multicellular) | 1 µm–10 m | Plasmodium, Giardia, Ascaris |
| Prions | Misfolded proteins (PrPSc); no nucleic acid | <100 nm | Creutzfeldt–Jakob disease (CJD), kuru |
Koch Postulates & Modern Modifications
Robert Koch established four criteria for attributing disease to a specific organism: (1) the organism is found in all cases of the disease; (2) it can be isolated and grown in pure culture; (3) inoculation into a susceptible host reproduces the disease; (4) the organism is re-isolated from the experimental host. Molecular Koch postulates extend these criteria to virulence genes using molecular genetics (e.g., gene knockout eliminates virulence, complementation restores it).
Prions are unique pathogens — they contain no nucleic acid, cannot be cultured, and are resistant to standard sterilization. They cause transmissible spongiform encephalopathies (TSEs) through conversion of normal PrPC to the misfolded PrPSc isoform. Diagnosis is by brain biopsy showing spongiform change; 14-3-3 protein and RT-QuIC assay in CSF are supportive.
02 Core Principles & Classification
Microorganisms are classified using a hierarchical taxonomy (domain, phylum, class, order, family, genus, species). In clinical practice, bacteria are classified by Gram stain (positive vs. negative), morphology (cocci, rods, spirals), oxygen requirements (aerobic, anaerobic, facultative), and biochemical tests (catalase, coagulase, oxidase, urease).
Gram Stain Fundamentals
The Gram stain is the single most important rapid diagnostic test in clinical microbiology. Crystal violet binds peptidoglycan; iodine fixes the dye; alcohol/acetone decolorizes thin-walled organisms; safranin counterstains decolorized cells pink.
| Property | Gram-Positive | Gram-Negative |
|---|---|---|
| Stain color | Purple/blue | Pink/red |
| Peptidoglycan thickness | 20–80 nm (thick) | 1–3 nm (thin) |
| Outer membrane | Absent | Present (contains LPS) |
| Teichoic acids | Present | Absent |
| Lipopolysaccharide (endotoxin) | Absent | Present (lipid A = toxic moiety) |
| Periplasmic space | Narrow | Wide |
| Susceptibility to penicillin | Generally more susceptible | Outer membrane barrier |
Oxygen Requirements
| Category | Definition | Examples |
|---|---|---|
| Obligate aerobe | Requires O2 for growth | Mycobacterium tuberculosis, Nocardia, Pseudomonas |
| Obligate anaerobe | Killed by O2; lacks catalase and superoxide dismutase | Clostridium, Bacteroides, Actinomyces |
| Facultative anaerobe | Grows with or without O2 (uses O2 when available) | E. coli, Staphylococcus, Streptococcus |
| Microaerophilic | Requires low O2 (5–10%) | Helicobacter pylori, Campylobacter |
| Aerotolerant anaerobe | Anaerobic metabolism, but tolerates O2 | Lactobacillus, Streptococcus (some) |
Key Biochemical Tests
| Test | Reaction | Clinical Use |
|---|---|---|
| Catalase | H2O2 → H2O + O2 (bubbles) | Staphylococcus (+) vs. Streptococcus (−) |
| Coagulase | Converts fibrinogen → fibrin (clot) | S. aureus (+) vs. CoNS (−) |
| Oxidase | Detects cytochrome c oxidase | Pseudomonas (+), Neisseria (+), Enterobacterales (−) |
| Urease | Urea → NH3 + CO2 | H. pylori, Proteus, Klebsiella, Ureaplasma |
| Optochin | Inhibits growth | S. pneumoniae (sensitive) vs. other alpha-hemolytic strep (resistant) |
| Bacitracin | Inhibits growth | S. pyogenes (GAS; sensitive) vs. other beta-hemolytic strep |
| Bile solubility | Autolysis in bile salts | S. pneumoniae (soluble) vs. Enterococcus (resistant) |
Quick mnemonic for catalase-positive organisms: Staphylococci are catalase-positive (bubbles); Streptococci and Enterococci are catalase-negative. Next, coagulase separates S. aureus (coagulase-positive) from coagulase-negative staphylococci (CoNS) such as S. epidermidis and S. saprophyticus.
Bacterial Genetics & Horizontal Gene Transfer
Bacteria acquire resistance and virulence genes through horizontal gene transfer mechanisms that operate independently of vertical (parent-to-offspring) inheritance:
| Mechanism | Description | Clinical Significance |
|---|---|---|
| Transformation | Uptake of free (naked) DNA from the environment | S. pneumoniae (Griffith experiment); penicillin resistance via PBP gene uptake |
| Transduction | DNA transfer via bacteriophage (virus) | Generalized: random DNA packaging; Specialized: adjacent genes transferred (e.g., shiga-like toxin in EHEC, diphtheria toxin from β-prophage) |
| Conjugation | Direct cell-to-cell transfer via sex pilus (F plasmid) | Plasmid-mediated resistance (ESBL genes, carbapenemase genes like KPC, NDM); most clinically significant mechanism |
| Transposition | Movement of transposable elements ("jumping genes") within or between DNA molecules | vanA gene in VRE; insertion sequences disrupting porin genes |
Microbial Culture Media Summary
| Medium | Type | Selects/Differentiates |
|---|---|---|
| Blood agar | Enriched, differential | Hemolysis patterns (α, β, γ) |
| Chocolate agar | Enriched (lysed RBCs release factors X and V) | Neisseria, Haemophilus |
| MacConkey agar | Selective and differential | Gram-negative rods; lactose fermenters (pink) vs. non-fermenters (colorless) |
| Eosin methylene blue (EMB) | Selective and differential | Gram-negative rods; E. coli = green metallic sheen |
| Thayer–Martin (VCN) agar | Selective chocolate agar | Neisseria (vancomycin, colistin, nystatin inhibit normal flora) |
| Hektoen enteric / XLD agar | Selective and differential | Salmonella and Shigella (H2S production) |
| Mannitol salt agar | Selective (7.5% NaCl) | Staphylococci; S. aureus ferments mannitol (yellow) |
| Bile esculin agar | Selective and differential | Enterococcus and S. bovis (group D strep) — hydrolyze esculin in bile |
Diagnostic Approach Algorithm
Gram stain → morphology (cocci vs. rods, clusters vs. chains) → catalase test (if Gram-positive cocci) → coagulase (if catalase-positive) or hemolysis/Lancefield grouping (if catalase-negative). For Gram-negative organisms: oxidase test separates fermenters (Enterobacterales, oxidase-negative) from non-fermenters (Pseudomonas, oxidase-positive). Lactose fermentation on MacConkey further differentiates Enterobacterales.
03 Bacterial Cell Structure & Physiology
Understanding bacterial cell architecture is essential because virtually every antibiotic targets a specific structural or metabolic component. The cell wall, cell membrane, ribosomes, and nucleic acid machinery are the principal drug targets.
Cell Wall Components
| Structure | Function | Drug Target |
|---|---|---|
| Peptidoglycan | Structural rigidity; NAG-NAM polymer cross-linked by peptide bridges | Beta-lactams (PBPs), vancomycin (D-Ala-D-Ala), bacitracin |
| Lipopolysaccharide (LPS) | Outer membrane of Gram-negatives; endotoxin (lipid A) | Polymyxins (colistin) disrupt outer membrane |
| Mycolic acid | Waxy coat of mycobacteria; acid-fast staining | Isoniazid (synthesis), ethambutol (arabinosyl transferase) |
| Teichoic/lipoteichoic acid | Gram-positive cell wall; anchors wall to membrane | Daptomycin (depolarizes membrane) |
Virulence Factors
| Factor | Mechanism | Key Organisms |
|---|---|---|
| Capsule (polysaccharide) | Antiphagocytic; inhibits complement deposition | S. pneumoniae, N. meningitidis, Klebsiella, H. influenzae type b, Cryptococcus |
| Endotoxin (lipid A) | TLR4 activation → TNF-α, IL-1, IL-6 → septic shock, DIC | All Gram-negative bacteria |
| Exotoxins | Secreted proteins; A-B toxins, superantigens, membrane-damaging toxins | See toxin table below |
| Protein A | Binds Fc of IgG → prevents opsonization | S. aureus |
| M protein | Antiphagocytic; molecular mimicry → rheumatic fever | S. pyogenes |
| Pili / fimbriae | Adhesion to host epithelium | N. gonorrhoeae, E. coli (P pili → pyelonephritis) |
| Biofilm | Sessile bacterial communities; 100–1000× antibiotic resistance | S. epidermidis (prosthetics), P. aeruginosa (CF) |
| IgA protease | Cleaves secretory IgA at mucosal surfaces | N. meningitidis, N. gonorrhoeae, S. pneumoniae, H. influenzae |
High-Yield Exotoxins
| Toxin | Organism | Mechanism | Disease |
|---|---|---|---|
| Diphtheria toxin | C. diphtheriae | ADP-ribosylates EF-2 → inhibits protein synthesis | Pseudomembranous pharyngitis, myocarditis |
| Exotoxin A | P. aeruginosa | ADP-ribosylates EF-2 (same as diphtheria) | Pneumonia, wound infection |
| Cholera toxin | V. cholerae | ADP-ribosylates Gs → permanently activates adenylyl cyclase → ↑cAMP → secretory diarrhea | Rice-water diarrhea |
| Heat-labile toxin (LT) | ETEC | ADP-ribosylates Gs → ↑cAMP (like cholera toxin) | Traveler's diarrhea |
| Pertussis toxin | B. pertussis | ADP-ribosylates Gi → ↑cAMP; disables chemokine receptor signaling | Whooping cough, lymphocytosis |
| Shiga toxin | Shigella dysenteriae, EHEC (O157:H7) | Cleaves 28S rRNA of 60S ribosome → inhibits protein synthesis → endothelial damage | Bloody diarrhea, HUS |
| Tetanospasmin | C. tetani | Blocks release of inhibitory neurotransmitters (GABA, glycine) at Renshaw cells | Spastic paralysis (tetanus) |
| Botulinum toxin | C. botulinum | Blocks ACh release at NMJ (cleaves SNARE proteins) | Flaccid paralysis (botulism) |
| TSST-1 | S. aureus | Superantigen → nonspecific T-cell activation → massive cytokine release | Toxic shock syndrome |
| Alpha toxin | C. perfringens | Lecithinase (phospholipase C) → destroys cell membranes | Gas gangrene (myonecrosis) |
| Erythrogenic toxin (SpeA/B/C) | S. pyogenes | Superantigen → rash and fever | Scarlet fever, streptococcal TSS |
Toxin Classification Memory Aid
ADP-ribosylating toxins — remember "Cholera, Diphtheria, Pertussis, Pseudomonas" all ADP-ribosylate host proteins. Cholera and heat-labile toxin target Gs (↑cAMP); pertussis targets Gi (↑cAMP by a different mechanism); diphtheria and Pseudomonas exotoxin A target EF-2 (↓protein synthesis).
04 Staphylococci
Staphylococci are Gram-positive cocci in clusters, catalase-positive, and facultative anaerobes. S. aureus is the most virulent species and is distinguished from coagulase-negative staphylococci (CoNS) by the coagulase test.
Staphylococcus aureus
| Feature | Detail |
|---|---|
| Gram stain | Gram-positive cocci in clusters |
| Key tests | Catalase (+), coagulase (+), mannitol fermentation (+), golden pigment on agar |
| Virulence factors | Protein A, coagulase, hemolysins (α, β, γ, δ), TSST-1, exfoliative toxin, PVL (Panton–Valentine leukocidin), enterotoxins (A–E) |
| Diseases | Skin/soft tissue (furuncles, carbuncles, impetigo, cellulitis), bacteremia, endocarditis, osteomyelitis, septic arthritis, pneumonia, food poisoning (preformed enterotoxin), toxic shock syndrome, scalded skin syndrome |
| MRSA | mecA gene encodes PBP2a with low affinity for beta-lactams; SCCmec cassette |
| Treatment (MSSA) | Nafcillin/oxacillin or cefazolin |
| Treatment (MRSA) | Vancomycin, daptomycin, linezolid, TMP-SMX (skin), doxycycline (skin) |
S. aureus food poisoning is caused by preformed heat-stable enterotoxin — symptoms occur within 1–6 hours of ingestion (rapid onset vomiting, no fever). This distinguishes it from most other bacterial food poisoning, which has a longer incubation.
Coagulase-Negative Staphylococci
| Species | Key Feature | Clinical Significance |
|---|---|---|
| S. epidermidis | Biofilm producer on prosthetic devices | Prosthetic valve endocarditis, catheter-related BSI, prosthetic joint infections |
| S. saprophyticus | Novobiocin-resistant; urease (+) | UTI in sexually active young women (second most common cause after E. coli) |
| S. lugdunensis | More virulent than typical CoNS | Aggressive native valve endocarditis; treat like S. aureus |
S. saprophyticus is novobiocin-resistant — this distinguishes it from S. epidermidis (novobiocin-sensitive). Think "SaP = Pee" for its association with UTI.
Staphylococcal Toxin-Mediated Diseases
| Disease | Toxin | Mechanism | Clinical Features |
|---|---|---|---|
| Toxic shock syndrome | TSST-1 (superantigen) | Nonspecific crosslinking of MHC II and TCR → massive T-cell activation → cytokine storm | High fever, diffuse macular rash with desquamation, hypotension, multiorgan involvement; associated with tampon use or wound packing |
| Scalded skin syndrome (SSSS) | Exfoliative toxin (ET-A, ET-B) | Serine protease cleaving desmoglein-1 in granular layer of epidermis | Widespread blistering and exfoliation in neonates/children; Nikolsky sign positive; no mucosal involvement (distinguishes from TEN) |
| Food poisoning | Enterotoxins (A most common) | Preformed heat-stable toxin → stimulates vagus nerve and CNS vomiting center | Rapid onset (1–6 hrs), violent vomiting, no fever; self-limited (24 hrs) |
| Bullous impetigo | Exfoliative toxin (localized) | Local epidermal cleavage | Large flaccid bullae on skin; more common in children |
05 Streptococci & Enterococci
Streptococci are Gram-positive cocci in chains or pairs, catalase-negative. They are classified by hemolysis pattern (α, β, γ) and Lancefield grouping (carbohydrate antigens A–V).
Hemolysis Patterns
| Pattern | Appearance | Organisms |
|---|---|---|
| α-hemolysis | Green/partial clearing around colonies | S. pneumoniae, S. viridans group |
| β-hemolysis | Complete clearing around colonies | S. pyogenes (GAS), S. agalactiae (GBS) |
| γ-hemolysis | No hemolysis | Enterococcus, some group D strep |
Major Streptococcal Species
| Organism | Group | Key Features | Diseases | Treatment |
|---|---|---|---|---|
| S. pyogenes | Group A | Bacitracin-sensitive, PYR (+), M protein, SpeA superantigen | Pharyngitis, scarlet fever, impetigo, cellulitis, necrotizing fasciitis, rheumatic fever, post-streptococcal GN | Penicillin (no resistance); clindamycin added for toxin suppression in severe cases |
| S. agalactiae | Group B | Bacitracin-resistant, CAMP test (+), hippurate hydrolysis (+) | Neonatal meningitis/sepsis, chorioamnionitis, UTI in pregnancy | Penicillin/ampicillin; GBS screening at 36–37 weeks |
| S. pneumoniae | — | α-hemolytic, lancet-shaped diplococci, optochin-sensitive, bile-soluble, quellung reaction (+) | Pneumonia (#1 CAP), meningitis, otitis media, sinusitis | Penicillin (if susceptible), ceftriaxone, vancomycin + ceftriaxone (meningitis) |
| Viridans group | — | α-hemolytic, optochin-resistant, bile-insoluble | Subacute bacterial endocarditis (damaged valves), dental caries (S. mutans) | Penicillin + gentamicin (endocarditis) |
| Enterococcus | Group D | Grows in bile and 6.5% NaCl, PYR (+), γ-hemolytic | UTI, biliary tract infections, endocarditis, intra-abdominal infections | Ampicillin ± gentamicin; vancomycin for resistant strains; linezolid or daptomycin for VRE |
Rheumatic Fever Criteria (Jones)
Major: Joint involvement (migratory polyarthritis), Carditis, Nodules (subcutaneous), Erythema marginatum, Sydenham chorea — mnemonic "JONES." Minor: Fever, elevated ESR/CRP, prolonged PR interval, arthralgias. Requires evidence of prior GAS infection + 2 major OR 1 major + 2 minor criteria.
Rheumatic fever follows GAS pharyngitis only (not skin infections). Post-streptococcal glomerulonephritis can follow either pharyngitis or skin infection. Penicillin prophylaxis prevents recurrent rheumatic fever but does not prevent initial PSGN episodes.
Streptococcal Post-Infectious Syndromes
| Syndrome | Pathogenesis | Timing | Key Features |
|---|---|---|---|
| Acute rheumatic fever | Molecular mimicry (M protein resembles cardiac myosin, laminin, and brain tissue) | 2–4 weeks after GAS pharyngitis | Carditis (pancarditis), migratory polyarthritis, erythema marginatum, subcutaneous nodules, Sydenham chorea; Aschoff bodies on histology |
| Post-streptococcal glomerulonephritis | Type III hypersensitivity (immune complex deposition in glomeruli) | 1–3 weeks after pharyngitis; 3–6 weeks after skin infection | Cola-colored urine (hematuria), periorbital edema, hypertension, low C3; "lumpy-bumpy" IF pattern (subepithelial humps on EM) |
| PANDAS | Autoimmune neuropsychiatric disorder associated with streptococcal infection | Days to weeks after GAS infection | Abrupt onset OCD and/or tics in prepubertal children |
Streptococcus bovis (gallolyticus) & Colon Cancer
S. bovis/gallolyticus bacteremia or endocarditis is strongly associated with colorectal carcinoma or other GI malignancies. Every patient with S. bovis bacteremia requires a colonoscopy. S. bovis is a group D streptococcus that grows in bile but NOT in 6.5% NaCl (distinguishing it from Enterococcus).
06 Gram-Positive Rods & Anaerobes
Gram-positive rods include aerobic and anaerobic species. The spore-forming genera (Bacillus, Clostridium) are especially important because spores confer environmental resistance.
Aerobic Gram-Positive Rods
| Organism | Key Features | Disease | Treatment |
|---|---|---|---|
| Bacillus anthracis | Spore-forming, encapsulated (poly-D-glutamate — only polypeptide capsule), nonhemolytic | Cutaneous anthrax (black eschar), pulmonary anthrax (woolsorter's disease), GI anthrax | Ciprofloxacin or doxycycline |
| Bacillus cereus | Spore-forming, produces emetic and diarrheagenic toxins | Emetic form: reheated rice (1–6 hr onset); diarrheal form: meats/vegetables (8–16 hr onset) | Supportive (self-limited) |
| Listeria monocytogenes | Tumbling motility at 25°C, grows at 4°C (refrigerator), β-hemolytic, facultative intracellular | Meningitis (neonates, elderly, immunocompromised), bacteremia, granulomatosis infantisepticum | Ampicillin ± gentamicin (NOT cephalosporins — natural resistance) |
| Corynebacterium diphtheriae | Club-shaped, metachromatic granules (Babes-Ernst), toxin encoded by β-prophage | Pseudomembranous pharyngitis, myocarditis, neuropathy | Antitoxin + erythromycin or penicillin |
| Nocardia | Weakly acid-fast, branching filamentous rods, aerobic | Pulmonary nocardiosis (mimics TB), brain abscess, cutaneous infection | TMP-SMX (first-line) |
Anaerobic Gram-Positive Rods (Clostridia)
| Organism | Toxin/Mechanism | Disease | Treatment |
|---|---|---|---|
| C. tetani | Tetanospasmin → blocks inhibitory NT release (glycine, GABA) | Tetanus (spastic paralysis, risus sardonicus, opisthotonus) | Tetanus Ig + metronidazole + wound debridement + supportive care |
| C. botulinum | Botulinum toxin → blocks ACh release (SNARE proteins) | Flaccid descending paralysis; foodborne, wound, infant (floppy baby) | Antitoxin (adults); BabyBIG (infant botulism); supportive (intubation if needed) |
| C. perfringens | Alpha toxin (lecithinase/phospholipase C) | Gas gangrene (myonecrosis), food poisoning (watery diarrhea) | Clindamycin + penicillin + surgical debridement |
| C. difficile | Toxin A (enterotoxin) + Toxin B (cytotoxin) | Antibiotic-associated pseudomembranous colitis | Vancomycin (oral) or fidaxomicin (oral); metronidazole for non-severe; bezlotoxumab for recurrence prevention |
Listeria is naturally resistant to cephalosporins — this is why empiric meningitis therapy in neonates and adults >50 years must include ampicillin (in addition to ceftriaxone + vancomycin) to cover Listeria. Food sources include unpasteurized dairy, deli meats, and soft cheeses.
Actinomyces & Other Gram-Positive Anaerobes
| Organism | Key Features | Disease | Treatment |
|---|---|---|---|
| Actinomyces israelii | Branching filamentous rods; NOT acid-fast (distinguishes from Nocardia); anaerobic; normal oral flora | Cervicofacial actinomycosis (draining sinus tracts with "sulfur granules" in jaw); thoracic, abdominal, pelvic (IUD-associated) | Penicillin G (prolonged course, 6–12 months); surgical drainage of abscesses |
| Clostridioides difficile | Spore-forming; toxigenic strains produce toxin A (enterotoxin) and toxin B (cytotoxin); NAP1/B1/027 hypervirulent strain produces binary toxin | Antibiotic-associated diarrhea, pseudomembranous colitis; risk factors: antibiotics (clindamycin, fluoroquinolones, cephalosporins), PPI use, hospitalization, age >65 | Initial non-severe: vancomycin PO or fidaxomicin PO; severe: vancomycin PO; fulminant: vancomycin PO + IV metronidazole ± rectal vancomycin; recurrent: fidaxomicin, bezlotoxumab, fecal microbiota transplant |
Nocardia vs. Actinomyces
Both are branching filamentous Gram-positive rods, but they differ in critical ways: Nocardia is aerobic, weakly acid-fast, found in soil, and causes pulmonary/brain disease in immunocompromised patients (treat with TMP-SMX). Actinomyces is anaerobic, NOT acid-fast, is normal oral flora, and causes draining sinus tracts (treat with penicillin). Confusion between these two is a common board question trap.
07 Enterobacterales
The Enterobacterales (formerly Enterobacteriaceae) are Gram-negative rods, facultative anaerobes, oxidase-negative, and glucose-fermenting. They are the most common cause of urinary tract infections, intra-abdominal infections, and Gram-negative bacteremia.
Key Enterobacterales
| Organism | Key Features | Diseases | Notes |
|---|---|---|---|
| E. coli | Most common GNR in clinical specimens; lactose-fermenter, green metallic sheen on EMB agar | UTI (#1 cause), neonatal meningitis (K1 capsule), bacteremia, traveler's diarrhea (ETEC), bloody diarrhea/HUS (EHEC O157:H7) | EHEC: do NOT give antibiotics (increases HUS risk) |
| Klebsiella pneumoniae | Large mucoid capsule, lactose-fermenter, currant jelly sputum | Pneumonia (alcoholics, diabetics), UTI, liver abscess (hypervirulent strains K1/K2) | Rising carbapenem resistance (KPC); inherent ampicillin resistance |
| Proteus mirabilis | Urease (+), swarming motility, non-lactose-fermenter | UTI (alkaline urine → staghorn calculi — struvite stones) | Urease splits urea → ammonia → alkaline pH → Mg-ammonium-phosphate stones |
| Salmonella typhi | Non-lactose-fermenter, H2S producer, intracellular pathogen | Typhoid fever (enteric fever): stepwise fever, relative bradycardia, rose spots, hepatosplenomegaly | Fluoroquinolone or azithromycin; sickle cell patients at risk for osteomyelitis |
| Salmonella (non-typhoidal) | Animal reservoir, eggs/poultry | Gastroenteritis (inflammatory diarrhea), bacteremia in immunocompromised | Usually self-limited; antibiotics prolong carriage in uncomplicated cases |
| Shigella | Very low infectious dose (10–100 organisms), no animal reservoir | Bacillary dysentery (bloody mucoid diarrhea), reactive arthritis, HUS (S. dysenteriae) | Fluoroquinolone or azithromycin for severe cases |
| Yersinia enterocolitica | Grows at 4°C (cold enrichment) | Mesenteric lymphadenitis (mimics appendicitis in children), bloody diarrhea | Contaminated pork, pet feces |
| Enterobacter, Citrobacter, Serratia | AmpC β-lactamase producers (inducible chromosomal) | Nosocomial infections (pneumonia, UTI, bacteremia) | "SPACE" organisms (Serratia, Pseudomonas, Acinetobacter, Citrobacter, Enterobacter) — avoid cephalosporins (AmpC induction) |
Curved Gram-Negative Rods
| Organism | Key Features | Disease | Treatment |
|---|---|---|---|
| Campylobacter jejuni | Comma-/S-shaped, microaerophilic, grows at 42°C, oxidase (+) | #1 cause of bacterial gastroenteritis in US; bloody diarrhea; associated with Guillain–Barré syndrome (molecular mimicry with ganglioside GM1) and reactive arthritis | Azithromycin (preferred); fluoroquinolone resistance increasing |
| Vibrio cholerae | Comma-shaped, oxidase (+), grows in alkaline media (TCBS agar) | Cholera: profuse rice-water diarrhea, severe dehydration, metabolic acidosis | Oral rehydration therapy (cornerstone); doxycycline or azithromycin (shortens duration) |
| Vibrio vulnificus | Halophilic (saltwater) | Wound infections from saltwater/shellfish; septicemia in liver disease (cirrhosis, hemochromatosis) — high mortality | Doxycycline + ceftriaxone |
| Vibrio parahaemolyticus | Halophilic; undercooked seafood | Gastroenteritis (watery or bloody diarrhea) | Usually self-limited; doxycycline if severe |
| Helicobacter pylori | Urease (+), microaerophilic, spiral-shaped; lives in gastric mucus layer | Peptic ulcer disease (#1 cause), chronic gastritis, gastric adenocarcinoma, gastric MALT lymphoma | Triple therapy: PPI + clarithromycin + amoxicillin (or metronidazole); bismuth quadruple therapy as alternative; urea breath test for diagnosis/cure confirmation |
Vibrio vulnificus causes rapidly progressive cellulitis and sepsis in patients with liver disease (cirrhosis) or iron overload (hemochromatosis) who eat raw oysters or sustain saltwater wound exposure. Mortality exceeds 50% in septic patients. Warn cirrhotic patients to avoid raw shellfish.
Diarrheagenic E. coli Pathotypes
ETEC: Traveler's diarrhea (heat-labile & heat-stable toxins → watery diarrhea). EHEC (O157:H7): Shiga-like toxin → bloody diarrhea, HUS; no antibiotics. EIEC: Invades colonic mucosa (Shigella-like). EPEC: Effacing lesions in infant diarrhea. EAEC: Aggregative adherence, persistent diarrhea in children.
08 Non-Fermenting Gram-Negative Rods
Non-fermenters are Gram-negative rods that cannot ferment glucose. They are typically oxidase-positive and are important causes of nosocomial infections, particularly in the ICU. Intrinsic multidrug resistance is a hallmark.
| Organism | Key Features | Diseases | Treatment |
|---|---|---|---|
| Pseudomonas aeruginosa | Oxidase (+), blue-green pigment (pyocyanin, pyoverdin), grape-like odor, biofilm in CF lungs | HAP/VAP, burns, otitis externa (swimmer's ear), hot tub folliculitis, ecthyma gangrenosum (neutropenic), CF pulmonary infections | Anti-pseudomonal penicillins (piperacillin-tazobactam), cefepime, ceftazidime, meropenem, ciprofloxacin, aminoglycosides; combination therapy for serious infections |
| Acinetobacter baumannii | Coccobacillary, survives on dry surfaces for weeks, war wound pathogen | HAP/VAP, wound infections, bacteremia (ICU settings) | Often XDR; ampicillin-sulbactam, polymyxins (colistin), tigecycline |
| Stenotrophomonas maltophilia | Intrinsic carbapenem resistance (metalloprotease L1 + L2) | HAP, bacteremia (immunocompromised) | TMP-SMX (first-line) |
| Burkholderia cepacia | Catalase (+), oxidase (+) | CF pulmonary infections (poor prognosis, contraindication to lung transplant) | TMP-SMX, meropenem |
Pseudomonas must be covered empirically in neutropenic fever, ventilator-associated pneumonia, and CF exacerbations. Ecthyma gangrenosum — necrotic skin lesions with black eschar in a febrile neutropenic patient — is pathognomonic for Pseudomonas bacteremia until proven otherwise.
Anti-Pseudomonal Antibiotics
Not all beta-lactams cover Pseudomonas. The following agents have reliable anti-pseudomonal activity:
| Class | Anti-Pseudomonal Agent(s) | Non-Anti-Pseudomonal (Common Pitfall) |
|---|---|---|
| Penicillins | Piperacillin-tazobactam, ticarcillin-clavulanate | Ampicillin, amoxicillin, nafcillin |
| Cephalosporins | Ceftazidime (3rd gen), cefepime (4th gen) | Ceftriaxone (3rd gen — NOT anti-pseudomonal), cefazolin |
| Carbapenems | Meropenem, imipenem, doripenem | Ertapenem (does NOT cover Pseudomonas) |
| Fluoroquinolones | Ciprofloxacin (most potent), levofloxacin | Moxifloxacin (no Pseudomonas coverage) |
| Aminoglycosides | Tobramycin, amikacin, gentamicin | — |
| Monobactams | Aztreonam | — |
09 Gram-Negative Cocci & Fastidious Organisms
Neisseria Species
| Organism | Key Features | Disease | Treatment |
|---|---|---|---|
| N. meningitidis | Gram-negative diplococci, oxidase (+), maltose-fermenter, polysaccharide capsule (serogroups A, B, C, W, Y) | Meningitis, meningococcemia (purpura fulminans, Waterhouse–Friderichsen syndrome — adrenal hemorrhage), DIC | Ceftriaxone; rifampin/ciprofloxacin for close contact prophylaxis; vaccines (MenACWY, MenB) |
| N. gonorrhoeae | Gram-negative diplococci, oxidase (+), does NOT ferment maltose, Thayer-Martin agar | Urethritis, cervicitis, PID, disseminated gonococcal infection (septic arthritis, skin lesions), ophthalmia neonatorum | Ceftriaxone 500 mg IM (single dose); treat presumptively for chlamydia co-infection |
| Moraxella catarrhalis | Gram-negative diplococci, oxidase (+), β-lactamase producer | Otitis media, sinusitis, COPD exacerbation | Amoxicillin-clavulanate (due to β-lactamase) |
Fastidious Gram-Negative Organisms
| Organism | Key Features | Disease | Treatment |
|---|---|---|---|
| Haemophilus influenzae | Requires factors X (hemin) and V (NAD) for growth; type b capsulated (invasive); nontypeable (mucosal) | Meningitis, epiglottitis (type b — now rare with Hib vaccine), otitis media, sinusitis, pneumonia (nontypeable) | Ceftriaxone (invasive); amoxicillin-clavulanate (otitis); rifampin prophylaxis for contacts |
| Bordetella pertussis | Bordet–Gengou agar, lymphocyte-promoting factor | Whooping cough: catarrhal → paroxysmal → convalescent stages; lymphocytosis | Macrolides (azithromycin); DTaP/Tdap vaccine |
| Legionella pneumophila | Intracellular (macrophages), buffered charcoal yeast extract (BCYE) agar, silver stain, Legionella urinary antigen (serogroup 1) | Legionnaires' disease (severe atypical pneumonia), Pontiac fever (mild flu-like illness) | Azithromycin or fluoroquinolone |
| Brucella | Intracellular, occupational (dairy farmers, veterinarians) | Undulant fever, hepatosplenomegaly, osteomyelitis (vertebral) | Doxycycline + rifampin (or streptomycin) |
| Francisella tularensis | Very low infectious dose, tick/rabbit exposure | Tularemia: ulceroglandular (most common), pneumonic, oculoglandular | Streptomycin or gentamicin |
| Pasteurella multocida | Normal oral flora of cats and dogs | Cellulitis/wound infection after animal bite (rapid onset, <24 hours) | Amoxicillin-clavulanate |
N. meningitidis ferments both glucose and maltose; N. gonorrhoeae ferments only glucose. Waterhouse–Friderichsen syndrome (bilateral adrenal hemorrhage from DIC) is a dreaded complication of meningococcemia — presents with acute adrenal crisis, purpura fulminans, and cardiovascular collapse.
10 Anaerobic Gram-Negative Bacteria
Anaerobic Gram-negative bacteria are normal flora of the GI tract, oral cavity, and female genital tract. They cause disease when they gain access to normally sterile sites, often in the setting of disrupted mucosal barriers.
| Organism | Key Features | Diseases | Treatment |
|---|---|---|---|
| Bacteroides fragilis | Most common anaerobic isolate in clinical specimens; polysaccharide capsule; β-lactamase producer | Intra-abdominal abscess, peritonitis, pelvic abscess, bacteremia | Metronidazole, carbapenems, piperacillin-tazobactam, ampicillin-sulbactam |
| Fusobacterium necrophorum | Gram-negative rod, normal pharyngeal flora | Lemierre syndrome: septic thrombophlebitis of the internal jugular vein after pharyngitis; septic emboli to lungs | Metronidazole + beta-lactam; anticoagulation controversial |
| Prevotella | Pigmented Gram-negative rod | Oral/dental infections, aspiration pneumonia, lung abscess | Metronidazole, clindamycin, carbapenems |
Clues to Anaerobic Infection
Foul-smelling discharge, gas in tissue, infection near mucosal surface, polymicrobial Gram stain, failure to grow on routine aerobic culture, abscess formation, history of aspiration. Anaerobes are the most common organisms in lung abscess and brain abscess.
11 Mycobacterium tuberculosis
M. tuberculosis is an obligate aerobe with a mycolic acid-rich cell wall that makes it acid-fast (Ziehl–Neelsen stain: red bacilli). It grows slowly (doubling time 15–20 hours; culture takes 2–6 weeks on Löwenstein–Jensen media). One-quarter of the world's population has latent TB infection.
Pathogenesis
Inhaled droplet nuclei reach alveoli → engulfed by alveolar macrophages → cord factor (trehalose dimycolate) prevents phagolysosome fusion → intracellular replication → Th1 immune response (IL-12, IFN-γ) activates macrophages → granuloma formation (caseating). Ghon focus (primary lung lesion) + Ghon complex (Ghon focus + ipsilateral hilar lymphadenopathy) = primary TB. Ranke complex = calcified Ghon complex (healed primary TB).
Diagnosis
| Test | Mechanism | Notes |
|---|---|---|
| TST (PPD/Mantoux) | Type IV (delayed-type) hypersensitivity to purified protein derivative | ≥5 mm (HIV, close contacts, CXR changes); ≥10 mm (high-risk groups); ≥15 mm (low risk); read at 48–72 hrs |
| IGRA (QuantiFERON-TB Gold, T-SPOT) | Measures IFN-γ release by T cells after TB antigen stimulation | Not affected by prior BCG vaccination (more specific); single blood draw |
| AFB smear | Ziehl–Neelsen or auramine-rhodamine fluorescent stain | 3 sputum specimens (8–24 hr apart); sensitivity 50–80% |
| NAAT (GeneXpert MTB/RIF) | PCR for M. tuberculosis and rifampin resistance | Results in 2 hours; WHO-recommended as initial diagnostic |
| Culture | Lowenstein–Jensen (solid) or BACTEC MGIT (liquid) | Gold standard; allows drug susceptibility testing; takes 2–6 weeks |
Treatment
Standard TB Regimen (RIPE)
Intensive phase (2 months): Rifampin + Isoniazid + Pyrazinamide + Ethambutol. Continuation phase (4 months): Rifampin + Isoniazid. Total = 6 months. Add pyridoxine (B6) with isoniazid to prevent peripheral neuropathy. Monitor LFTs (INH, RIF, PZA all hepatotoxic), visual acuity (ethambutol → optic neuritis), uric acid (PZA).
Rifampin is a potent CYP450 inducer — it reduces the efficacy of oral contraceptives, warfarin, HIV protease inhibitors, and many other drugs. Isoniazid is metabolized by N-acetyltransferase (NAT2): slow acetylators have higher drug levels and more toxicity (hepatitis, peripheral neuropathy).
12 Non-Tuberculous Mycobacteria
| Organism | Key Features | Disease | Treatment |
|---|---|---|---|
| M. avium complex (MAC) | Most common NTM; disseminated in AIDS when CD4 <50 | Disseminated MAC (fever, weight loss, hepatosplenomegaly, pancytopenia); pulmonary MAC (Lady Windermere syndrome) | Azithromycin + ethambutol ± rifabutin; azithromycin prophylaxis when CD4 <50 |
| M. kansasii | Photochromogen (pigment in light) | Pulmonary disease resembling TB | Isoniazid + rifampin + ethambutol |
| M. marinum | Grows at 30°C (lower than body temp) | Fish tank granuloma (skin nodules on hands) | Ethambutol + clarithromycin or rifampin |
| M. leprae | Cannot be cultured in vitro; grows in armadillos and in cooler body sites (skin, peripheral nerves) | Leprosy: tuberculoid (Th1, few organisms, granulomas) vs. lepromatous (Th2, many organisms, leonine facies) | Tuberculoid: dapsone + rifampin (6 months); Lepromatous: dapsone + rifampin + clofazimine (12 months) |
| M. scrofulaceum | Scotochromogen (pigment in dark) | Cervical lymphadenitis in children (scrofula) | Surgical excision (first-line) |
M. leprae infects Schwann cells — peripheral neuropathy is the hallmark. Tuberculoid leprosy has a strong Th1 response with few bacilli and well-formed granulomas; lepromatous has a Th2 response with many bacilli and poorly formed granulomas (failed cell-mediated immunity). Lepromin test is positive in tuberculoid but negative in lepromatous.
13 Spirochetes, Rickettsiae & Atypicals
Spirochetes
| Organism | Key Features | Disease | Treatment |
|---|---|---|---|
| Treponema pallidum | Cannot be cultured; darkfield microscopy, FTA-ABS, RPR/VDRL | Syphilis: Primary (painless chancre) → Secondary (diffuse rash including palms/soles, condylomata lata) → Tertiary (gummas, aortitis, tabes dorsalis, Argyll Robertson pupils) | Penicillin G (all stages); Jarisch–Herxheimer reaction after treatment |
| Borrelia burgdorferi | Ixodes tick vector, largest spirochete | Lyme disease: Stage 1 (erythema migrans); Stage 2 (carditis, Bell palsy, meningitis); Stage 3 (arthritis, encephalopathy) | Doxycycline (early); ceftriaxone (neurologic/cardiac) |
| Leptospira interrogans | Question-mark shaped; animal urine exposure | Leptospirosis: biphasic illness, Weil disease (hepatorenal failure, hemorrhage) | Penicillin or doxycycline |
Rickettsiae & Obligate Intracellular Bacteria
| Organism | Vector | Disease | Key Features | Treatment |
|---|---|---|---|---|
| Rickettsia rickettsii | Dermacentor tick | Rocky Mountain spotted fever | Rash starts on wrists/ankles → centripetal (to trunk); "spotted fever" triad: fever, rash, headache | Doxycycline (even in children) |
| R. prowazekii | Body louse | Epidemic typhus | Rash starts on trunk → centrifugal; war/poverty/crowding | Doxycycline |
| Coxiella burnetii | No arthropod vector; inhalation of contaminated aerosols (farm animals) | Q fever: atypical pneumonia, hepatitis, culture-negative endocarditis (chronic) | Doxycycline; chronic Q fever: doxycycline + hydroxychloroquine (18+ months) | |
| Ehrlichia chaffeensis | Lone Star tick | Human monocytic ehrlichiosis | Infects monocytes; morulae (mulberry-like inclusions); leukopenia, thrombocytopenia | Doxycycline |
| Anaplasma phagocytophilum | Ixodes tick | Human granulocytic anaplasmosis | Infects neutrophils; morulae in granulocytes | Doxycycline |
Atypical Bacteria (Cell-Wall-Deficient)
| Organism | Key Features | Disease | Treatment |
|---|---|---|---|
| Mycoplasma pneumoniae | No cell wall (no peptidoglycan → beta-lactam resistant); smallest free-living organism; Eaton agar | Atypical (walking) pneumonia in young adults; cold agglutinins (IgM vs. RBC I antigen) | Macrolides (azithromycin), doxycycline, fluoroquinolones |
| Chlamydia trachomatis | Obligate intracellular; elementary body (infectious) → reticulate body (replicative) | Serotypes A–C (trachoma); D–K (urethritis, cervicitis, PID, neonatal conjunctivitis/pneumonia); L1–L3 (lymphogranuloma venereum) | Azithromycin or doxycycline |
| Chlamydophila pneumoniae | Respiratory droplet transmission | Atypical pneumonia (community-acquired) | Macrolide or doxycycline |
| Chlamydophila psittaci | Bird exposure (parrots, parakeets) | Psittacosis (atypical pneumonia) | Doxycycline |
For all rickettsial diseases, doxycycline is the treatment of choice — even in children and pregnant women when the diagnosis is strongly suspected, because the mortality of untreated RMSF exceeds 20%. Do not wait for serologic confirmation to treat.
Zoonotic Bacteria Summary
| Organism | Animal Reservoir | Vector/Exposure | Disease |
|---|---|---|---|
| Bartonella henselae | Cat | Cat scratch/bite; flea transmission between cats | Cat scratch disease (regional lymphadenopathy); bacillary angiomatosis (AIDS); peliosis hepatis |
| Yersinia pestis | Prairie dogs, rats | Flea bite | Plague: bubonic (inguinal buboes), pneumonic, septicemic |
| Borrelia burgdorferi | White-footed mouse, deer | Ixodes tick | Lyme disease |
| Leptospira | Rats, dogs | Contact with animal urine, contaminated water | Leptospirosis, Weil disease |
| Brucella | Cattle, goats, pigs | Unpasteurized dairy, occupational (farmers, vets) | Undulant fever, vertebral osteomyelitis |
| Coxiella burnetii | Cattle, sheep, goats | Inhalation of aerosols from animal products (no arthropod vector needed) | Q fever |
| Chlamydophila psittaci | Birds (parrots, parakeets) | Inhalation of dried bird droppings | Psittacosis (atypical pneumonia) |
Bartonella in HIV/AIDS
Bartonella henselae and B. quintana cause bacillary angiomatosis in AIDS patients — vascular proliferative lesions of the skin that can mimic Kaposi sarcoma. Unlike KS (caused by HHV-8), bacillary angiomatosis is curable with antibiotics (doxycycline or erythromycin). Biopsy with Warthin–Starry silver stain shows clumps of bacteria. B. quintana also causes trench fever (transmitted by body lice) and culture-negative endocarditis in homeless populations.
14 DNA Viruses
DNA viruses generally replicate in the nucleus (exception: poxviruses replicate in cytoplasm — they carry their own DNA-dependent RNA polymerase). All DNA viruses are double-stranded except parvoviruses (ssDNA). All are icosahedral except poxviruses (complex). Mnemonic for enveloped DNA viruses: "HHPPox" — Herpesviruses, Hepadnaviruses, Poxviruses.
| Family | Envelope | Genome | Key Viruses | Diseases |
|---|---|---|---|---|
| Herpesviridae | Yes | dsDNA, linear | HSV-1, HSV-2, VZV, EBV, CMV, HHV-6, HHV-8 | See herpesvirus table below |
| Adenoviridae | No | dsDNA, linear | Adenovirus (serotypes 1–57) | Pharyngoconjunctival fever, keratoconjunctivitis, pneumonia (military recruits), hemorrhagic cystitis |
| Papillomaviridae | No | dsDNA, circular | HPV (types 6,11 = warts; 16,18 = cervical cancer) | Warts (verrucae), cervical/anal/oropharyngeal cancer, condylomata acuminata |
| Polyomaviridae | No | dsDNA, circular | JC virus, BK virus | JC: PML in immunocompromised; BK: hemorrhagic cystitis (transplant), nephropathy |
| Poxviridae | Yes (complex) | dsDNA, linear | Variola (smallpox), molluscum contagiosum, monkeypox | Smallpox (eradicated), molluscum (umbilicated papules), mpox |
| Hepadnaviridae | Yes | Partially dsDNA, circular | Hepatitis B virus | Hepatitis B (see hepatitis section) |
| Parvoviridae | No | ssDNA, linear | Parvovirus B19 | Fifth disease (erythema infectiosum, "slapped cheeks"), aplastic crisis (sickle cell), hydrops fetalis |
Herpesviruses
| Virus | Latency Site | Primary Disease | Reactivation | Treatment |
|---|---|---|---|---|
| HSV-1 (HHV-1) | Trigeminal ganglia | Oral herpes (gingivostomatitis), herpes keratitis | Cold sores (herpes labialis), encephalitis (temporal lobe) | Acyclovir, valacyclovir |
| HSV-2 (HHV-2) | Sacral ganglia | Genital herpes, neonatal herpes | Genital ulcers | Acyclovir, valacyclovir |
| VZV (HHV-3) | Dorsal root ganglia | Varicella (chickenpox) | Herpes zoster (shingles) — dermatomal | Acyclovir, valacyclovir; Shingrix vaccine |
| EBV (HHV-4) | B cells | Infectious mononucleosis (fever, pharyngitis, lymphadenopathy, hepatosplenomegaly, atypical lymphocytes) | Oral hairy leukoplakia; associated with Burkitt lymphoma, nasopharyngeal carcinoma, Hodgkin lymphoma, PTLD | Supportive; avoid contact sports (splenic rupture risk) |
| CMV (HHV-5) | Mononuclear cells | Mononucleosis-like (heterophile-negative), congenital CMV (hearing loss, periventricular calcifications) | Retinitis, colitis, esophagitis, pneumonitis (transplant/AIDS) | Ganciclovir, valganciclovir, foscarnet |
| HHV-6 | T cells | Roseola infantum (exanthem subitum): high fever → rash appears as fever breaks | Encephalitis (transplant) | Ganciclovir, foscarnet |
| HHV-8 | B cells | Kaposi sarcoma (AIDS-defining), primary effusion lymphoma, multicentric Castleman disease | — | Treat underlying HIV; chemotherapy for advanced KS |
Oncogenic Viruses
| Virus | Genome | Associated Cancer | Mechanism |
|---|---|---|---|
| HPV (16, 18) | dsDNA | Cervical, anal, oropharyngeal, vulvar, penile carcinoma | E6 protein degrades p53; E7 protein inhibits Rb → uncontrolled cell cycle progression |
| EBV (HHV-4) | dsDNA | Burkitt lymphoma (c-myc translocation t(8;14)), nasopharyngeal carcinoma, Hodgkin lymphoma, PTLD, primary CNS lymphoma (AIDS) | LMP-1 mimics CD40 signaling → B-cell proliferation; EBNA proteins maintain latency |
| HHV-8 | dsDNA | Kaposi sarcoma, primary effusion lymphoma, multicentric Castleman disease | Viral homologs of cyclin D, FLIP, IL-6 promote proliferation and inhibit apoptosis |
| HBV | Partially dsDNA | Hepatocellular carcinoma | Chronic inflammation → regenerative nodules → cirrhosis → HCC; HBx protein activates oncogenic pathways |
| HCV | ssRNA | Hepatocellular carcinoma, non-Hodgkin lymphoma | Chronic inflammation → cirrhosis → HCC (always through cirrhosis, unlike HBV which can cause HCC without cirrhosis) |
| HTLV-1 | ssRNA (retrovirus) | Adult T-cell leukemia/lymphoma | Tax protein activates NF-κB → T-cell proliferation |
Vaccine-Preventable Cancers
HPV vaccine (9-valent Gardasil-9) prevents cervical, anal, and oropharyngeal cancers caused by high-risk HPV types 16 and 18 (plus 31, 33, 45, 52, 58). HBV vaccine prevents hepatitis B-associated hepatocellular carcinoma. These are the only two cancer-preventive vaccines currently in widespread use.
HSV encephalitis has a predilection for the temporal lobe — MRI shows temporal lobe hyperintensity. LP shows lymphocytic pleocytosis, elevated protein, and normal glucose; HSV PCR of CSF is the diagnostic test of choice. Start IV acyclovir empirically — do NOT wait for results.
15 RNA Viruses
RNA viruses are a diverse group. Most are single-stranded RNA; reoviruses are the exception (dsRNA). Negative-sense RNA viruses must carry their own RNA-dependent RNA polymerase (RdRp) to make mRNA. Positive-sense RNA viruses can serve directly as mRNA for translation.
Negative-Sense ssRNA Viruses
Mnemonic: "Always Bring Polymerase" — negative-sense viruses always bring their own polymerase.
| Family | Key Viruses | Diseases | Notes |
|---|---|---|---|
| Orthomyxoviridae | Influenza A, B, C | Influenza; antigenic drift (minor changes) and shift (major reassortment — pandemics) | Segmented genome (8 segments); oseltamivir (neuraminidase inhibitor), baloxavir |
| Paramyxoviridae | Parainfluenza, RSV, measles, mumps, hMPV | Parainfluenza: croup (steeple sign). RSV: bronchiolitis in infants. Measles: 3 Cs (cough, coryza, conjunctivitis) + Koplik spots + maculopapular rash. Mumps: parotitis, orchitis, aseptic meningitis | RSV: palivizumab (prophylaxis for premature infants), nirsevimab; measles: vitamin A |
| Rhabdoviridae | Rabies virus | Rabies: prodrome → acute neurologic phase (furious or paralytic) → coma → death | Bullet-shaped virus; Negri bodies (eosinophilic intracytoplasmic inclusions in Purkinje cells); PEP: rabies Ig + vaccine series |
| Filoviridae | Ebola, Marburg | Viral hemorrhagic fever with high case-fatality rate | BSL-4 pathogens; supportive care; Ebola vaccine (rVSV-ZEBOV) |
| Bunyavirales | Hantavirus, Crimean–Congo HF virus | Hantavirus pulmonary syndrome (deer mice, Four Corners region); hemorrhagic fever with renal syndrome | No person-to-person transmission for hantavirus; supportive care |
| Arenaviridae | Lymphocytic choriomeningitis virus (LCMV), Lassa virus | Aseptic meningitis (LCMV — hamster/mouse exposure); Lassa fever (West Africa) | Ribavirin for Lassa fever |
Positive-Sense ssRNA Viruses
| Family | Key Viruses | Diseases | Notes |
|---|---|---|---|
| Picornaviridae | Poliovirus, coxsackievirus, echovirus, rhinovirus, HAV | Polio: flaccid paralysis (anterior horn cells). Coxsackie A: hand-foot-mouth, herpangina. Coxsackie B: myocarditis, pericarditis ("B for Body" — heart). Rhinovirus: common cold. HAV: hepatitis A | Non-enveloped; fecal-oral transmission (polio, HAV, enteroviruses) |
| Flaviviridae | Dengue, Zika, West Nile, yellow fever, HCV | Dengue: break-bone fever, hemorrhagic fever. Zika: microcephaly. West Nile: meningoencephalitis, flaccid paralysis. Yellow fever: black vomit, Councilman bodies | Mosquito-borne (Aedes or Culex); HCV: direct-acting antivirals (sofosbuvir + ledipasvir/velpatasvir) |
| Togaviridae | Rubella, Chikungunya, Eastern/Western equine encephalitis | Rubella: congenital rubella syndrome (deafness, cataracts, PDA, blueberry muffin rash). Chikungunya: severe polyarthralgia | MMR vaccine for rubella |
| Coronaviridae | SARS-CoV-2, SARS-CoV, MERS-CoV, common cold coronaviruses | COVID-19: pneumonia, ARDS, multiorgan failure, long COVID | Largest RNA genome; remdesivir, nirmatrelvir/ritonavir (Paxlovid); mRNA vaccines |
| Caliciviridae | Norovirus | #1 cause of viral gastroenteritis worldwide (outbreaks in cruise ships, schools) | Non-enveloped; highly contagious; supportive care |
| Reoviridae | Rotavirus | #1 cause of severe infantile gastroenteritis worldwide | dsRNA (double-stranded — only dsRNA virus); non-enveloped; live oral vaccine |
Only RNA virus that is double-stranded: rotavirus (Reoviridae). Only RNA virus with a segmented genome among common pathogens: influenza (Orthomyxoviridae) — segmentation enables antigenic shift through reassortment. Antigenic drift (point mutations) causes seasonal epidemics; antigenic shift (reassortment of genome segments) causes pandemics.
Key Viral Properties Summary
| Property | Viruses |
|---|---|
| Non-enveloped DNA viruses | Adenovirus, HPV, polyomavirus (JC/BK), parvovirus B19 — "PAP" smear (Papilloma, Adeno, Parvo) plus Polyoma |
| Enveloped DNA viruses | Herpesviruses, HBV, Poxviruses — "HHPPox" |
| Non-enveloped RNA viruses | Picornavirus, calicivirus (norovirus), reovirus (rotavirus), astrovirus, HEV |
| Segmented RNA viruses | Influenza (8 segments), rotavirus (11 segments), bunyaviruses, arenaviruses |
| Viruses replicating in cytoplasm | All RNA viruses (except influenza, which uses host nuclear machinery for mRNA capping) and poxviruses (DNA but cytoplasmic) |
| Viruses with reverse transcriptase | HIV (retrovirus, RNA → DNA), HBV (hepadnavirus, DNA → RNA → DNA) |
| Naked (non-enveloped) viruses are resistant to | Detergents, desiccation, acid (GI tract); enveloped viruses are fragile |
16 Retroviruses & HIV
Retroviruses are enveloped, positive-sense ssRNA viruses that carry reverse transcriptase to convert RNA → DNA, which integrates into the host genome via integrase.
HIV Virology & Pathogenesis
| Feature | Detail |
|---|---|
| Structure | gp120 (binds CD4), gp41 (fusion), p24 (capsid — detected in acute infection), p17 (matrix) |
| Co-receptors | CCR5 (macrophage-tropic, early) and CXCR4 (T-cell-tropic, late) |
| Target cells | CD4+ T cells, macrophages, dendritic cells |
| Enzymes | Reverse transcriptase, integrase, protease |
| Natural history | Acute retroviral syndrome (2–4 weeks) → clinical latency (years) → AIDS (CD4 <200 or AIDS-defining illness) |
HIV Diagnosis
4th-generation assay: HIV-1/2 Ag/Ab combo test (detects both p24 antigen and HIV antibodies) → if reactive, HIV-1/HIV-2 antibody differentiation assay → if indeterminate, HIV-1 RNA (NAT). Window period: 4th-gen assay detects infection ~2 weeks after exposure (p24 antigenemia).
Antiretroviral Drug Classes
| Class | Mechanism | Examples | Key Side Effects |
|---|---|---|---|
| NRTIs | Nucleoside/nucleotide analog → chain termination of reverse transcription | Tenofovir (TDF, TAF), emtricitabine, abacavir, lamivudine, zidovudine | TDF: nephrotoxicity, Fanconi syndrome; ZDV: bone marrow suppression; abacavir: HLA-B*5701 hypersensitivity |
| NNRTIs | Bind allosteric site on RT | Efavirenz, rilpivirine, doravirine | Efavirenz: vivid dreams, CNS effects; all NNRTIs: rash |
| Protease inhibitors | Block cleavage of viral polyproteins | Atazanavir, darunavir (boosted with ritonavir or cobicistat) | Lipodystrophy, hyperglycemia, hyperlipidemia; ritonavir: CYP3A4 inhibitor |
| Integrase inhibitors (INSTIs) | Block viral DNA integration into host genome | Dolutegravir, bictegravir, raltegravir, cabotegravir | Generally well-tolerated; preferred first-line class; dolutegravir: weight gain |
| Entry inhibitors | Block viral entry | Maraviroc (CCR5 antagonist), enfuvirtide (fusion inhibitor), ibalizumab (post-attachment inhibitor) | Maraviroc: requires tropism testing; enfuvirtide: injection site reactions |
AIDS-Defining Conditions by CD4 Count
CD4 <500: Oral thrush (Candida), hairy leukoplakia (EBV). CD4 <200: PCP (Pneumocystis jirovecii), Kaposi sarcoma (HHV-8), histoplasmosis. CD4 <100: Toxoplasmosis, cryptosporidiosis, cryptococcal meningitis. CD4 <50: MAC, CMV retinitis, CNS lymphoma (EBV-associated).
17 Hepatitis Viruses
| Virus | Family | Genome | Transmission | Chronicity | Key Features |
|---|---|---|---|---|---|
| HAV | Picornavirus | ssRNA (+) | Fecal-oral | No | Self-limited; no chronic state; IgM anti-HAV = acute; vaccine available |
| HBV | Hepadnavirus | Partially dsDNA | Blood, sexual, vertical | Yes (5% adults, 90% neonates) | Reverse transcriptase; HBsAg (infection), anti-HBs (immunity), HBeAg (high infectivity), anti-HBc IgM (acute); associated with hepatocellular carcinoma and PAN |
| HCV | Flavivirus | ssRNA (+) | Blood (IVDU #1) | Yes (75–85%) | No vaccine; curable with direct-acting antivirals (DAAs); associated with HCC, cryoglobulinemia, membranoproliferative GN |
| HDV | Deltavirus | ssRNA (−), circular | Blood, sexual | Only with HBV co-infection | Defective virus; requires HBsAg coat; co-infection or superinfection of HBV carrier (superinfection more severe) |
| HEV | Hepeviridae | ssRNA (+) | Fecal-oral (waterborne) | No (except immunocompromised) | Especially dangerous in pregnant women (mortality up to 20% in 3rd trimester) |
HBV Serologic Interpretation
| HBsAg | Anti-HBs | Anti-HBc IgM | Anti-HBc IgG | Interpretation |
|---|---|---|---|---|
| + | − | + | − | Acute HBV infection |
| + | − | − | + | Chronic HBV infection |
| − | + | − | + | Recovered (immune from natural infection) |
| − | + | − | − | Vaccinated (immune) |
| − | − | + | − | Window period (acute) |
| − | − | − | − | Susceptible (not immune) |
The window period of HBV occurs when HBsAg has cleared but anti-HBs has not yet appeared. During this time, anti-HBc IgM is the only marker of acute infection. Vaccination produces only anti-HBs (no anti-HBc, because core antigen is not in the vaccine).
Hepatitis B e Antigen & DNA Interpretation
| Phase | HBsAg | HBeAg | HBV DNA | ALT | Interpretation |
|---|---|---|---|---|---|
| Immune tolerant | + | + | Very high | Normal | High viral replication, minimal liver damage; common in perinatally infected |
| Immune active (HBeAg+) | + | + | High | Elevated | Active liver damage; consider treatment |
| Inactive carrier | + | − | Low (<2000 IU/mL) | Normal | Seroconversion to anti-HBe; low risk of progression |
| HBeAg-negative chronic hepatitis | + | − | Moderate-high | Elevated | Pre-core/core promoter mutant; reactivation-prone; treat |
HBV Reactivation Risk
Patients with chronic HBV (HBsAg+) or past HBV (anti-HBc+ only) are at risk for HBV reactivation when given immunosuppressive therapy, especially rituximab (anti-CD20), high-dose corticosteroids, and TNF inhibitors. Screen all patients for HBV before starting immunosuppressive therapy. Prophylaxis with entecavir or tenofovir prevents reactivation.
18 Systemic (Endemic) Mycoses
The systemic (dimorphic) fungi are mold at 25°C (environmental) and yeast at 37°C (body temperature) — "mold in the cold, yeast in the heat." They cause disease in immunocompetent individuals and are geographically restricted.
| Organism | Geography | Exposure | Disease | Diagnosis | Treatment |
|---|---|---|---|---|---|
| Histoplasma capsulatum | Ohio & Mississippi River valleys; Central America | Bat/bird droppings, cave exploration, demolition of old buildings | Acute pulmonary (flu-like), chronic cavitary, disseminated (immunocompromised — hepatosplenomegaly, pancytopenia) | Urine/serum Histoplasma antigen; oval yeast within macrophages; methenamine silver stain | Mild: itraconazole; severe/disseminated: amphotericin B then itraconazole |
| Blastomyces dermatitidis | Great Lakes, Ohio & Mississippi River valleys | Rotting wood, soil near waterways | Pulmonary (mimics pneumonia/cancer), skin (verrucous/ulcerative lesions), bone | Broad-based budding yeast (thick refractile walls) | Mild: itraconazole; severe: amphotericin B then itraconazole |
| Coccidioides immitis | Southwestern US (Arizona, California), Mexico | Soil dust inhalation (desert, earthquakes, construction) | Valley fever: pulmonary (cough, fever, erythema nodosum, arthralgias "desert rheumatism"); disseminated (meningitis) | Spherules containing endospores on biopsy; coccidioidin skin test; serology (complement fixation) | Mild: often self-limited or fluconazole; severe/meningeal: amphotericin B (intrathecal for meningitis) + fluconazole (lifelong for meningitis) |
| Paracoccidioides brasiliensis | Latin America | Soil, agricultural workers | Chronic pulmonary, mucocutaneous lesions (mulberry-like oral lesions) | "Captain's wheel" yeast (multiple buds surrounding parent cell) | Itraconazole or TMP-SMX |
| Talaromyces (Penicillium) marneffei | Southeast Asia | Bamboo rat exposure | Disseminated infection in AIDS (skin papules with central umbilication, mimics molluscum) | Yeast with central septum (divides by fission, not budding) | Amphotericin B then itraconazole |
Coccidioides meningitis requires lifelong fluconazole — relapse is nearly universal if treatment is stopped. Erythema nodosum (tender red nodules on shins) in a patient from the Southwest should prompt consideration of coccidioidomycosis.
Endemic Mycoses Geography Mnemonic
Think "Ohio/Mississippi = Histo and Blasto" (river valley fungi). "Southwest desert = Cocci" (Valley fever). Histoplasma is the most commonly tested endemic mycosis. Key exposure: spelunking (caves) or demolition of old buildings with bat/bird droppings. Organisms live in macrophages (similar to TB) — look for oval yeast within macrophages on silver stain.
Dimorphic Fungi: Key Histologic Features
| Organism | Yeast Form (37°C) | Mold Form (25°C) |
|---|---|---|
| Histoplasma | Small oval yeast inside macrophages (2–4 µm) | Tuberculate macroconidia |
| Blastomyces | Broad-based budding yeast (8–15 µm); thick, double-refractile walls | Hyphae with conidia |
| Coccidioides | Spherules (20–60 µm) filled with endospores (NOT true yeast) | Hyphae with arthroconidia (barrel-shaped; highly infectious) |
| Paracoccidioides | "Captain's wheel" or "mariner's wheel" — large yeast with multiple peripheral buds | Hyphae with conidia |
| Sporothrix | Cigar-shaped budding yeast | Rosette conidia ("daisy" pattern) |
19 Opportunistic Fungi
Opportunistic fungi cause disease primarily in immunocompromised hosts (neutropenia, HIV/AIDS, transplant recipients, chronic corticosteroid use).
| Organism | Morphology | Disease | Diagnosis | Treatment |
|---|---|---|---|---|
| Candida albicans | Yeast with pseudohyphae and true hyphae; germ tube (+) | Oral thrush, esophagitis, vulvovaginal candidiasis, candidemia, catheter-related BSI, hepatosplenic candidiasis | Germ tube test, culture, beta-D-glucan, T2Candida | Fluconazole (mucosal); echinocandin (candidemia); amphotericin B (resistant species) |
| Candida auris | Multi-drug resistant yeast; environmental persistence | Candidemia, wound infections, ear infections | Often misidentified by standard methods; MALDI-TOF MS | Echinocandins (first-line); many strains resistant to fluconazole and amphotericin B |
| Aspergillus fumigatus | Septate hyphae branching at 45-degree (V-shaped) angles | Invasive aspergillosis (neutropenia), aspergilloma (fungus ball in cavities), ABPA (allergic bronchopulmonary aspergillosis — asthma + eosinophilia + high IgE) | Galactomannan antigen, beta-D-glucan, CT "halo sign" (early) → "air crescent sign" (recovery) | Voriconazole (first-line invasive); isavuconazole; ABPA: steroids + itraconazole |
| Cryptococcus neoformans | Encapsulated yeast; polysaccharide capsule (anti-phagocytic) | Cryptococcal meningitis (AIDS, CD4 <100); "soap bubble" lesions in brain | India ink stain (capsule halo), cryptococcal antigen (CrAg) in CSF/serum, mucicarmine stain | Induction: amphotericin B + flucytosine (2 weeks); consolidation: fluconazole (8 weeks); maintenance: fluconazole |
| Mucor/Rhizopus (Mucormycosis) | Non-septate (pauciseptate) hyphae branching at 90-degree (right) angles | Rhinocerebral mucormycosis (DKA, neutropenia); pulmonary, cutaneous | Tissue biopsy (ribbon-like hyphae); does NOT produce beta-D-glucan or galactomannan | Amphotericin B + aggressive surgical debridement; correct underlying condition (DKA) |
| Pneumocystis jirovecii | Atypical fungus (cannot be cultured on standard media) | PCP (Pneumocystis pneumonia) in AIDS (CD4 <200), transplant, prolonged steroids | Methenamine silver or DFA stain of BAL; beta-D-glucan elevated; bilateral ground-glass opacities on CT | TMP-SMX (first-line); alternatives: pentamidine, atovaquone, dapsone; add prednisone if PaO2 <70 or A-a gradient >35 |
Septate vs. Non-Septate Hyphae
Septate hyphae at 45 degrees (V-shaped) = Aspergillus. Non-septate (pauciseptate) hyphae at 90 degrees (right-angle branching) = Mucor/Rhizopus. This distinction is critical on biopsy and boards. Mucormycosis classically occurs in diabetic ketoacidosis (high glucose + acidosis + elevated iron = ideal growth conditions).
PCP prophylaxis with TMP-SMX is indicated when CD4 <200 cells/µL or CD4% <14% in HIV, and in transplant recipients or patients on prolonged high-dose corticosteroids. TMP-SMX also provides prophylaxis against Toxoplasma.
20 Superficial & Cutaneous Mycoses
| Organism/Condition | Clinical Presentation | Diagnosis | Treatment |
|---|---|---|---|
| Dermatophytes (Trichophyton, Microsporum, Epidermophyton) | Tinea capitis (scalp), tinea corporis (body — ringworm), tinea cruris (groin), tinea pedis (feet), tinea unguium/onychomycosis (nails) | KOH prep showing septate branching hyphae; Wood lamp (Microsporum fluoresces); dermatophyte culture on Sabouraud agar | Topical azoles/terbinafine (skin); oral terbinafine or griseofulvin (nails, scalp) |
| Malassezia furfur (Pityrosporum) | Tinea (pityriasis) versicolor: hypo- or hyperpigmented macules with fine scale, "spaghetti and meatballs" on KOH | KOH prep; Wood lamp (yellow-green fluorescence) | Topical selenium sulfide, ketoconazole shampoo; oral fluconazole for extensive disease |
| Sporothrix schenckii | Sporotrichosis: rose gardener's disease — painless papule at inoculation site → ascending lymphangitic spread (nodular lymphangitis) | Cigar-shaped budding yeast at 37°C; dimorphic (mold at 25°C) | Itraconazole (cutaneous); amphotericin B (disseminated) |
Tinea capitis in children requires oral antifungal therapy (topical agents do not penetrate the hair follicle). Griseofulvin has been the traditional first-line agent; terbinafine is an alternative. Kerion (inflammatory, boggy mass) is a severe form of tinea capitis that can be mistaken for a bacterial abscess.
Dermatophyte Classification & Clinical Correlation
| Genus | Habitat | Common Species | Preferred Infection Site |
|---|---|---|---|
| Trichophyton | Anthropophilic (human-adapted) | T. rubrum (#1 cause of dermatophytosis), T. tonsurans (tinea capitis in US), T. mentagrophytes | Skin, hair, nails (infects all keratinized tissue) |
| Microsporum | Zoophilic (animal sources) | M. canis (from cats/dogs), M. audouinii | Skin, hair (NOT nails); fluoresces under Wood lamp |
| Epidermophyton | Anthropophilic | E. floccosum | Skin, nails (NOT hair) |
KOH Preparation
KOH (potassium hydroxide) dissolves keratin and cellular debris, allowing visualization of fungal elements. A positive KOH prep from a skin scraping shows septate, branching hyphae in dermatophyte infections. For tinea versicolor (Malassezia), KOH shows the characteristic "spaghetti and meatballs" pattern (short hyphae and round yeast cells). KOH is rapid and inexpensive but has lower sensitivity than culture.
21 Protozoa
Protozoa are single-celled eukaryotic parasites. They are classified by mode of motility: amoebae (pseudopods), flagellates (flagella), ciliates (cilia), and sporozoans/apicomplexa (non-motile, intracellular).
Blood & Tissue Protozoa
| Organism | Vector/Transmission | Disease | Diagnosis | Treatment |
|---|---|---|---|---|
| Plasmodium (P. falciparum, P. vivax, P. ovale, P. malariae, P. knowlesi) | Female Anopheles mosquito | Malaria: cyclic fevers, anemia, splenomegaly; P. falciparum: severe malaria (cerebral, ARDS, blackwater fever); P. vivax/ovale: hypnozoites in liver (relapse) | Thick and thin blood smears; rapid diagnostic test (RDT) for HRP-2 antigen | P. falciparum: ACT (artemisinin-based combination therapy) or IV artesunate (severe); P. vivax/ovale: chloroquine + primaquine (hypnozoites — check G6PD first) |
| Toxoplasma gondii | Cat feces (oocysts), undercooked meat (tissue cysts), vertical (congenital) | Toxoplasmosis: ring-enhancing brain lesions (AIDS, CD4 <100); congenital toxo (chorioretinitis, hydrocephalus, intracranial calcifications) | Serology (IgG/IgM); brain MRI (multiple ring-enhancing lesions) | Pyrimethamine + sulfadiazine + leucovorin; TMP-SMX for prophylaxis |
| Trypanosoma cruzi | Triatomine (reduviid/"kissing bug") | Chagas disease: acute (Romana sign — periorbital swelling), chronic (dilated cardiomyopathy, megaesophagus, megacolon) | Blood smear (trypomastigotes), serology | Benznidazole or nifurtimox (acute phase) |
| Trypanosoma brucei | Tsetse fly | African sleeping sickness: Stage 1 (hemolymphatic — chancre, fever, lymphadenopathy); Stage 2 (CNS — somnolence, coma) | Blood smear; CSF examination for CNS involvement | Stage 1: suramin (East African) or pentamidine (West African); Stage 2: melarsoprol or eflornithine |
| Leishmania | Sandfly | Visceral (kala-azar: fever, hepatosplenomegaly, pancytopenia), cutaneous (ulcers), mucocutaneous | Amastigotes in macrophages (bone marrow, spleen biopsy) | Amphotericin B (liposomal) for visceral; miltefosine |
| Babesia microti | Ixodes tick (same as Lyme) | Babesiosis: hemolytic anemia, fever; severe in asplenic patients | Blood smear: intraerythrocytic ring forms, "Maltese cross" (tetrad); PCR | Atovaquone + azithromycin; clindamycin + quinine (severe) |
Intestinal Protozoa
| Organism | Transmission | Disease | Diagnosis | Treatment |
|---|---|---|---|---|
| Entamoeba histolytica | Fecal-oral (cysts in water) | Amebic dysentery (bloody diarrhea, flask-shaped ulcers), liver abscess (anchovy paste, RUQ pain) | Stool O&P (trophozoites with ingested RBCs), serology, stool antigen | Metronidazole + luminal agent (paromomycin or iodoquinol) |
| Giardia lamblia | Fecal-oral (cysts in water — hikers, daycare) | Watery, foul-smelling, fatty diarrhea (steatorrhea); no blood; bloating, flatulence | Stool O&P (pear-shaped trophozoites), stool antigen (ELISA) | Metronidazole or tinidazole |
| Cryptosporidium parvum | Fecal-oral; resistant to chlorination | Watery diarrhea (self-limited in immunocompetent; severe chronic in AIDS) | Modified acid-fast stain of stool (oocysts); stool antigen | Nitazoxanide (immunocompetent); immune reconstitution with ART (AIDS) |
| Trichomonas vaginalis | Sexual transmission (STI) | Vaginitis: green-yellow frothy discharge, strawberry cervix, pH >4.5 | Wet mount (motile trophozoites), NAAT (most sensitive) | Metronidazole (treat both partners) |
Cryptosporidium oocysts are resistant to chlorination — this is why waterborne outbreaks occur even in treated municipal water. Modified acid-fast stain is the key diagnostic test (oocysts stain red). In HIV/AIDS patients, the only effective treatment is immune reconstitution with antiretroviral therapy.
CNS Protozoa
| Organism | Host/Setting | Presentation | Diagnosis | Treatment |
|---|---|---|---|---|
| Toxoplasma gondii | AIDS (CD4 <100) | Multiple ring-enhancing brain lesions (basal ganglia); headache, focal deficits, seizures | Brain MRI; serology (IgG usually positive); empiric treatment trial (improvement in 2 weeks supports diagnosis vs. lymphoma) | Pyrimethamine + sulfadiazine + leucovorin |
| Naegleria fowleri | Healthy individuals; warm freshwater | Rapidly fatal meningoencephalitis (PAM); CSF: neutrophilic pleocytosis, low glucose, motile trophozoites | CSF wet mount; negative bacterial cultures | Amphotericin B + miltefosine (rarely successful) |
| Trypanosoma brucei | Sub-Saharan Africa; tsetse fly | Sleeping sickness; daytime somnolence, behavioral changes, coma | Blood/CSF trypomastigotes; Winterbottom sign (posterior cervical lymphadenopathy) | Stage 2: melarsoprol (East African) or eflornithine (West African) |
| Plasmodium falciparum | Tropical/subtropical | Cerebral malaria: altered consciousness, seizures, coma; high parasitemia | Thick/thin smear; banana-shaped gametocytes (P. falciparum) | IV artesunate (severe malaria) |
Malaria Species Comparison
| Feature | P. falciparum | P. vivax / P. ovale | P. malariae |
|---|---|---|---|
| Severity | Most severe; cerebral malaria, ARDS, severe anemia | Moderate | Mild; nephrotic syndrome |
| Fever cycle | Irregular or daily (malignant tertian) | Every 48 hr (benign tertian) | Every 72 hr (quartan) |
| RBC preference | All ages of RBCs (high parasitemia) | Reticulocytes | Older RBCs |
| Hypnozoites (liver dormancy) | No | Yes — requires primaquine for radical cure | No |
| Banana-shaped gametocytes | Yes (pathognomonic) | No | No |
Before giving primaquine or tafenoquine for P. vivax/ovale radical cure, always check G6PD levels. These drugs cause oxidative hemolysis in G6PD-deficient patients. P. falciparum malaria can progress rapidly to death — any patient with suspected severe malaria should receive IV artesunate immediately while confirmatory testing is pending.
22 Helminths
Helminths are multicellular parasitic worms classified as nematodes (roundworms), cestodes (tapeworms), and trematodes (flukes). A hallmark of helminthic infections is eosinophilia.
Nematodes (Roundworms)
| Organism | Transmission | Disease | Diagnosis | Treatment |
|---|---|---|---|---|
| Ascaris lumbricoides | Fecal-oral (eggs in soil) | Most common helminth worldwide; intestinal obstruction (worm bolus), Loeffler syndrome (pulmonary eosinophilia during larval migration), biliary/pancreatic obstruction | Stool O&P (fertilized eggs) | Albendazole or mebendazole |
| Enterobius vermicularis | Fecal-oral (autoinfection) | Pinworm: perianal itching (worse at night when female deposits eggs) | Scotch tape test (eggs on perianal skin, collected in morning) | Albendazole or mebendazole (treat household) |
| Strongyloides stercoralis | Skin penetration (larvae in soil) | Intestinal infection; hyperinfection syndrome in immunocompromised (especially corticosteroids) — disseminated disease, Gram-negative sepsis | Stool (larvae, not eggs — autoinfective cycle); serology | Ivermectin (first-line) |
| Ancylostoma/Necator (hookworms) | Skin penetration (walking barefoot) | Iron deficiency anemia (chronic blood loss); ground itch at entry site; eosinophilia | Stool O&P (eggs) | Albendazole or mebendazole |
| Trichinella spiralis | Ingestion of undercooked pork/game meat (encysted larvae) | Periorbital edema, myalgias, eosinophilia, splinter hemorrhages | Muscle biopsy (encysted larvae); serology; elevated CK, eosinophilia | Albendazole + corticosteroids (for severe inflammation) |
| Wuchereria bancrofti | Mosquito (Culex, Aedes, Anopheles) | Lymphatic filariasis (elephantiasis) | Blood smear (microfilariae — nocturnal periodicity) | Diethylcarbamazine (DEC) |
| Onchocerca volvulus | Blackfly (Simulium) | River blindness (onchocerciasis): subcutaneous nodules, pruritic dermatitis, corneal opacities | Skin snip biopsy (microfilariae) | Ivermectin (annual mass drug administration) |
| Toxocara canis/cati | Ingestion of eggs (dog/cat feces; children) | Visceral larva migrans (hepatomegaly, eosinophilia); ocular larva migrans | Serology; eosinophilia | Albendazole + corticosteroids |
Cestodes (Tapeworms) & Trematodes (Flukes)
| Organism | Transmission | Disease | Treatment |
|---|---|---|---|
| Taenia solium (pork tapeworm) | Undercooked pork (intestinal); fecal-oral eggs (cysticercosis) | Intestinal tapeworm; neurocysticercosis (seizures, ring-enhancing cysts in brain) | Intestinal: praziquantel; neurocysticercosis: albendazole + corticosteroids (reduce inflammation before antiparasitic) |
| Echinococcus granulosus | Dog feces (eggs); sheep as intermediate host | Hydatid cyst disease (liver > lung); anaphylaxis risk with cyst rupture | Albendazole + surgical/percutaneous aspiration (PAIR procedure); do NOT aspirate without antiparasitic coverage |
| Diphyllobothrium latum | Undercooked freshwater fish | Vitamin B12 deficiency (megaloblastic anemia) — tapeworm absorbs B12 | Praziquantel |
| Schistosoma | Freshwater snail intermediate host; cercariae penetrate skin | S. mansoni/japonicum: hepatic fibrosis (periportal/pipe-stem fibrosis), portal hypertension. S. haematobium: hematuria, bladder cancer (squamous cell carcinoma) | Praziquantel |
| Clonorchis sinensis | Undercooked freshwater fish | Biliary inflammation, cholangiocarcinoma | Praziquantel |
| Paragonimus westermani | Undercooked freshwater crab/crayfish | Lung fluke: hemoptysis, cavitary lung lesions (mimics TB) | Praziquantel |
Strongyloides hyperinfection syndrome occurs when immunosuppression (especially corticosteroids) accelerates the autoinfective cycle. Patients can develop disseminated disease with larvae invading virtually every organ, complicated by Gram-negative sepsis as intestinal bacteria translocate with migrating larvae. Screen for Strongyloides before starting immunosuppressive therapy in patients from endemic areas.
Nematode Larval Migration Patterns
Several nematodes have a pulmonary migration phase through the lungs that can cause Loeffler syndrome (transient pulmonary eosinophilia with cough, wheezing, and migratory infiltrates on CXR):
| Organism | Route of Entry | Migration Path | Key Features |
|---|---|---|---|
| Ascaris lumbricoides | Oral (eggs) | Intestine → portal vein → liver → lungs → swallowed → intestine (adult) | Loeffler syndrome; intestinal obstruction (worm bolus); most common helminth worldwide |
| Strongyloides stercoralis | Skin (larvae) | Skin → blood → lungs → swallowed → intestine; autoinfective cycle allows internal reinfection | Hyperinfection in immunosuppressed; only helminth that completes life cycle within human host |
| Ancylostoma/Necator (hookworm) | Skin (larvae) | Skin → blood → lungs → swallowed → intestine | Ground itch at entry; iron deficiency anemia from chronic intestinal blood loss |
| Toxocara | Oral (eggs) | Intestine → liver → lungs → systemic (cannot complete cycle in humans — dead-end host) | Visceral larva migrans (eosinophilia, hepatomegaly); ocular larva migrans |
Eosinophilia Differential in Helminth Infections
Marked eosinophilia (>1500/µL) is a hallmark of tissue-invasive helminths (those with a tissue migration phase). The most common causes include: Strongyloides, Ascaris (during migration), hookworms, Toxocara, Trichinella, filarial worms, and Schistosoma (acute Katayama fever). Protozoa generally do NOT cause eosinophilia (exception: Isospora belli).
23 Ectoparasites
| Organism | Clinical Presentation | Associated Diseases | Treatment |
|---|---|---|---|
| Sarcoptes scabiei | Scabies: intense pruritus (worse at night), burrows in web spaces, wrists, genitalia; crusted (Norwegian) scabies in immunocompromised | Secondary bacterial infection (GAS/S. aureus impetigo) | Permethrin 5% cream (first-line); ivermectin (oral, for crusted scabies); treat all close contacts |
| Pediculus humanus | Body lice (corporis): pruritus, excoriations; head lice (capitis): pruritus, nits on hair shafts | Body louse vectors epidemic typhus (R. prowazekii), trench fever (Bartonella quintana), relapsing fever (Borrelia recurrentis) | Permethrin; malathion; ivermectin (oral) |
| Phthirus pubis | Pubic (crab) lice: pruritus in genital area | STI co-infection screening | Permethrin; lice combing |
| Ticks (Ixodes, Dermacentor, Amblyomma, Lone Star) | Tick attachment and feeding | Lyme, RMSF, ehrlichiosis, anaplasmosis, babesiosis, tularemia, tick paralysis | Prompt tick removal (fine-tipped forceps); disease-specific treatment |
Crusted (Norwegian) scabies occurs in immunocompromised patients and the elderly — it is highly contagious due to the massive mite burden (millions vs. 10–15 mites in typical scabies). It presents as hyperkeratotic, crusted plaques rather than the classic burrows. Oral ivermectin is the treatment of choice for crusted scabies.
Free-Living Amoebae
| Organism | Exposure | Disease | Diagnosis | Treatment |
|---|---|---|---|---|
| Naegleria fowleri | Warm freshwater (lakes, hot springs, poorly maintained pools); enters via nasal passages (cribriform plate) | Primary amebic meningoencephalitis (PAM): rapidly fatal (>95% mortality); purulent CSF with motile trophozoites | CSF wet mount (motile trophozoites); negative bacterial cultures; brain biopsy | Amphotericin B (intrathecal + IV) + miltefosine; almost universally fatal despite treatment |
| Acanthamoeba | Contact lens solution (contaminated); freshwater | Granulomatous amebic encephalitis (subacute, immunocompromised); Acanthamoeba keratitis (contact lens wearers — severe eye pain) | Confocal microscopy (keratitis); brain biopsy (GAE); double-walled cysts | Keratitis: polyhexamethylene biguanide + propamidine; GAE: combination therapy (miltefosine, pentamidine, flucytosine) |
Naegleria fowleri PAM typically affects healthy young individuals who swim in warm freshwater. It presents like bacterial meningitis (headache, fever, nuchal rigidity) but CSF Gram stain is negative and cultures are sterile. CSF may show RBCs. Suspect when purulent meningitis has negative bacterial cultures and a history of freshwater exposure.
24 Antibacterial Mechanisms & Agents
Antibiotics are classified by their mechanism of action, which determines their spectrum, side effects, and resistance patterns. The five major targets are: (1) cell wall synthesis, (2) cell membrane, (3) protein synthesis (30S and 50S ribosomal subunits), (4) nucleic acid synthesis, and (5) metabolic pathways.
Cell Wall Synthesis Inhibitors
| Drug Class | Mechanism | Examples | Spectrum/Notes |
|---|---|---|---|
| Penicillins | Bind PBPs → inhibit transpeptidation of peptidoglycan | Penicillin G/V, ampicillin, amoxicillin, nafcillin/oxacillin, piperacillin-tazobactam | Narrow (PenG) to broad (pip-tazo); hypersensitivity reactions (type I most dangerous) |
| Cephalosporins | Same as penicillins (bind PBPs) | 1st: cefazolin; 2nd: cefoxitin; 3rd: ceftriaxone, ceftazidime; 4th: cefepime; 5th: ceftaroline (MRSA coverage) | Increasing Gram-negative coverage with each generation; 5% cross-reactivity with penicillin allergy (historical; actual <2%) |
| Carbapenems | Broadest beta-lactam spectrum | Meropenem, imipenem-cilastatin, ertapenem, doripenem | Ertapenem does NOT cover Pseudomonas or Acinetobacter; imipenem lowers seizure threshold |
| Monobactams | Binds PBP3 of Gram-negatives only | Aztreonam | Gram-negative only; safe in penicillin-allergic patients (no cross-reactivity) |
| Glycopeptides | Bind D-Ala-D-Ala terminus → block transglycosylation | Vancomycin, telavancin | Gram-positive only; "Red man syndrome" (histamine release with rapid infusion, NOT allergy); nephrotoxicity, ototoxicity |
Protein Synthesis Inhibitors
| Drug Class | Target | Effect | Examples | Key Side Effects |
|---|---|---|---|---|
| Aminoglycosides | 30S ribosome | Bactericidal; cause misreading of mRNA | Gentamicin, tobramycin, amikacin, streptomycin | Nephrotoxicity, ototoxicity (vestibular and cochlear), neuromuscular blockade |
| Tetracyclines | 30S ribosome | Bacteriostatic; block tRNA binding to A site | Doxycycline, minocycline, tigecycline | Photosensitivity, teeth discoloration (children <8), esophageal ulcers; doxycycline OK in renal failure |
| Macrolides | 50S ribosome | Bacteriostatic; block translocation | Azithromycin, clarithromycin, erythromycin | QT prolongation, GI upset; erythromycin: CYP3A4 inhibitor, pyloric stenosis risk in neonates |
| Chloramphenicol | 50S ribosome | Bacteriostatic; blocks peptidyl transferase | Chloramphenicol | Aplastic anemia (idiosyncratic), gray baby syndrome (glucuronidation deficiency in neonates) |
| Clindamycin | 50S ribosome | Bacteriostatic; blocks translocation | Clindamycin | C. difficile colitis; suppresses toxin production (used in necrotizing fasciitis) |
| Linezolid | 50S ribosome | Bacteriostatic; blocks initiation complex formation (23S rRNA of 50S) | Linezolid, tedizolid | Thrombocytopenia, serotonin syndrome (MAO inhibitor), peripheral neuropathy, optic neuritis |
Other Antibacterial Agents
| Drug Class | Mechanism | Examples | Key Notes |
|---|---|---|---|
| Fluoroquinolones | Inhibit DNA gyrase (topoisomerase II) and topoisomerase IV | Ciprofloxacin, levofloxacin, moxifloxacin | Tendon rupture (Achilles), QT prolongation, aortic dissection; cipro best for Pseudomonas; moxi best for respiratory (covers atypicals + anaerobes) |
| Metronidazole | Forms free radicals that damage DNA | Metronidazole | Anaerobes + protozoa; disulfiram-like reaction with alcohol; metallic taste |
| TMP-SMX | Sequential folate synthesis inhibition: SMX inhibits dihydropteroate synthase; TMP inhibits dihydrofolate reductase | Trimethoprim-sulfamethoxazole | MRSA skin infections, PCP prophylaxis/treatment, UTI; hyperkalemia (TMP blocks ENaC); sulfa allergy |
| Rifamycins | Inhibit DNA-dependent RNA polymerase | Rifampin, rifabutin, rifaximin | Potent CYP450 inducer (red/orange body fluids); TB backbone; rifaximin for hepatic encephalopathy and traveler's diarrhea |
| Daptomycin | Depolarizes cell membrane | Daptomycin | Bactericidal for Gram-positives; inactivated by surfactant (cannot use for pneumonia); monitor CK (myopathy) |
| Polymyxins | Disrupt outer membrane (detergent-like) | Colistin (polymyxin E), polymyxin B | Last resort for MDR Gram-negatives (Acinetobacter, Pseudomonas, CRE); nephrotoxicity, neurotoxicity |
Antibiotic Side Effects — High-Yield Board Associations
| Side Effect | Drug(s) | Mechanism/Notes |
|---|---|---|
| Red man syndrome | Vancomycin | Histamine release with rapid infusion; NOT a true allergy; slow the infusion rate |
| Tendon rupture (Achilles) | Fluoroquinolones | Risk increased with age >60, corticosteroids, renal disease; FDA black box warning |
| Ototoxicity + nephrotoxicity | Aminoglycosides | Monitor trough levels; once-daily dosing reduces toxicity |
| Gray baby syndrome | Chloramphenicol | Immature hepatic glucuronidation in neonates → drug accumulation → cardiovascular collapse |
| Teeth discoloration / bone growth inhibition | Tetracyclines | Chelates Ca2+; avoid in children <8 years and pregnancy (exception: doxycycline for RMSF is indicated regardless of age) |
| Peripheral neuropathy | Isoniazid, metronidazole, linezolid, nitrofurantoin | INH: prevent with pyridoxine (B6); metronidazole: cumulative dose-dependent |
| Photosensitivity | Doxycycline, voriconazole, TMP-SMX | Sun avoidance counseling; voriconazole: long-term use associated with skin cancer risk |
| QT prolongation | Macrolides (azithromycin, erythromycin), fluoroquinolones (moxi > levo) | Avoid combination with other QT-prolonging drugs |
| Disulfiram-like reaction | Metronidazole, cefotetan, cefoperazone | Inhibit aldehyde dehydrogenase; avoid alcohol during and 48 hr after treatment |
| C. difficile colitis | Clindamycin (#1), fluoroquinolones, cephalosporins, carbapenems | Disruption of normal gut flora allows C. difficile overgrowth; any antibiotic can cause it |
| Serotonin syndrome | Linezolid (MAO inhibitor) | Avoid with SSRIs, SNRIs, meperidine, tramadol |
| Bone marrow suppression | Chloramphenicol (aplastic anemia), linezolid (thrombocytopenia), ganciclovir (neutropenia), TMP-SMX (megaloblastic anemia) | Monitor CBC; TMP inhibits dihydrofolate reductase → folate deficiency |
The combination of vancomycin + piperacillin-tazobactam is associated with a higher rate of acute kidney injury compared to vancomycin + cefepime or vancomycin + meropenem. When possible, consider alternatives to this combination, especially in patients with baseline renal impairment.
Bactericidal vs. Bacteriostatic
Bactericidal agents kill bacteria: beta-lactams, vancomycin, aminoglycosides, fluoroquinolones, metronidazole, daptomycin. Bacteriostatic agents inhibit growth: macrolides, tetracyclines, clindamycin, chloramphenicol, linezolid, TMP-SMX. Bactericidal agents are preferred in meningitis, endocarditis, and neutropenic patients where host immune function is impaired.
25 Antimicrobial Resistance
Antimicrobial resistance is one of the greatest threats to global health. Understanding resistance mechanisms is essential for rational antibiotic selection and antimicrobial stewardship.
Major Resistance Mechanisms
| Mechanism | Description | Clinical Examples |
|---|---|---|
| Enzymatic inactivation | Bacteria produce enzymes that destroy or modify the antibiotic | Beta-lactamases (TEM, SHV), ESBLs (CTX-M), AmpC (chromosomal), carbapenemases (KPC, NDM, OXA-48), aminoglycoside-modifying enzymes |
| Target modification | Mutation or acquisition of altered target | PBP2a in MRSA (mecA); vanA/vanB in VRE (D-Ala-D-Lac replaces D-Ala-D-Ala); 23S rRNA methylation (erm genes → macrolide resistance) |
| Efflux pumps | Active export of antibiotic from cell | Tetracycline resistance; fluoroquinolone resistance in Pseudomonas; multidrug efflux pumps (MexAB-OprM) |
| Decreased permeability | Loss of outer membrane porins | OprD porin loss → carbapenem resistance in Pseudomonas; OmpK36 loss in Klebsiella |
| Target bypass | Acquisition of alternative pathway | VanA in VRE; mecA in MRSA |
Clinically Important Resistant Organisms
| Organism | Resistance | Mechanism | Treatment Options |
|---|---|---|---|
| MRSA | All beta-lactams (except ceftaroline) | mecA gene → PBP2a (low beta-lactam affinity) | Vancomycin, daptomycin, linezolid, TMP-SMX, doxycycline (skin), ceftaroline |
| VRE | Vancomycin | vanA (high-level, inducible) or vanB | Linezolid, daptomycin, tigecycline |
| ESBL-producing Enterobacterales | 3rd-generation cephalosporins, penicillins | Plasmid-borne CTX-M, TEM, SHV extended-spectrum beta-lactamases | Carbapenems (drug of choice for serious ESBL infections) |
| CRE (carbapenem-resistant Enterobacterales) | Carbapenems | KPC (serine carbapenemase), NDM/VIM/IMP (metallo-beta-lactamases) | Ceftazidime-avibactam (KPC), meropenem-vaborbactam, cefiderocol, polymyxins |
| MDR Pseudomonas | Multiple drug classes | Efflux pumps, AmpC, porin loss, metallo-beta-lactamases | Ceftolozane-tazobactam, ceftazidime-avibactam, cefiderocol, polymyxins |
| MDR Acinetobacter | Virtually all agents | OXA-type carbapenemases, efflux pumps | Ampicillin-sulbactam (intrinsic activity of sulbactam), polymyxins, tigecycline, cefiderocol |
ESKAPE Pathogens
Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. — the leading causes of nosocomial infections that "escape" commonly used antibiotics. These organisms are the primary focus of antimicrobial stewardship efforts and new drug development.
When an ESBL-producing organism is identified, switch to a carbapenem regardless of in vitro susceptibility to cephalosporins — clinical outcomes are better with carbapenems. For KPC-producing CRE, ceftazidime-avibactam is the preferred agent; for metallo-beta-lactamase producers (NDM, VIM), cefiderocol or aztreonam-based combinations are needed (avibactam does not inhibit metallo-beta-lactamases).
Beta-Lactamase Classification (Ambler)
| Class | Type | Examples | Inhibited By | Clinical Impact |
|---|---|---|---|---|
| A (serine) | Penicillinases, ESBLs, KPC | TEM-1, SHV-1, CTX-M, KPC-2 | Clavulanate, tazobactam, avibactam, vaborbactam | ESBLs hydrolyze 3rd-gen cephalosporins; KPC hydrolyzes carbapenems |
| B (metallo) | Metallo-beta-lactamases (require Zn2+) | NDM-1, VIM, IMP | NOT inhibited by clavulanate or avibactam; inhibited by EDTA (chelates zinc) | Hydrolyze all beta-lactams except aztreonam |
| C (serine) | AmpC cephalosporinases | Chromosomal AmpC (Enterobacter, Citrobacter, Serratia), plasmid CMY | Avibactam; NOT inhibited by clavulanate | Inducible resistance to 3rd-gen cephalosporins; "SPACE" organisms |
| D (serine) | OXA-type (oxacillinases) | OXA-48 (carbapenemase), OXA-23 (Acinetobacter) | Variably by avibactam | Major carbapenem resistance mechanism in Acinetobacter |
AmpC Induction — The "SPACE" Bug Pitfall
Serratia, Pseudomonas, Acinetobacter, Citrobacter, and Enterobacter carry chromosomal AmpC beta-lactamases. Exposure to 3rd-generation cephalosporins (e.g., ceftriaxone) can induce AmpC overexpression, leading to resistance during therapy. A patient with Enterobacter bacteremia may initially appear susceptible to ceftriaxone but develop resistance on treatment. Use cefepime (stable to AmpC) or carbapenems for serious SPACE infections.
Intrinsic (Natural) Resistance Patterns
| Organism | Intrinsic Resistance | Clinical Pearl |
|---|---|---|
| MRSA | All beta-lactams except ceftaroline | mecA → PBP2a |
| Enterococcus faecalis | Cephalosporins, aminoglycosides (low-level), TMP-SMX (in vivo) | Use ampicillin + gentamicin for synergy; cephalosporins have zero activity |
| Listeria | Cephalosporins | Must add ampicillin to meningitis regimen in neonates and elderly |
| Klebsiella | Ampicillin (chromosomal SHV-1 beta-lactamase) | Always resistant to ampicillin and amoxicillin |
| Proteus, Morganella, Providencia | Colistin/polymyxins | Intrinsic LPS modification; cannot use colistin as last resort |
| Stenotrophomonas | Carbapenems (L1 metallo-beta-lactamase) | TMP-SMX is first-line; one of few bugs where carbapenems worsen outcomes |
| Anaerobes | Aminoglycosides | Require O2-dependent transport into cells; no activity in anaerobic conditions |
| Mycoplasma | All cell wall-active agents (beta-lactams, vancomycin) | No peptidoglycan = no target |
26 Antifungal, Antiviral & Antiparasitic Agents
Antifungal Agents
| Drug Class | Mechanism | Examples | Key Uses & Side Effects |
|---|---|---|---|
| Polyenes | Bind ergosterol → membrane pore formation | Amphotericin B (liposomal preferred), nystatin (topical) | Broadest antifungal spectrum; nephrotoxicity (acute tubular necrosis), infusion reactions, hypokalemia, hypomagnesemia |
| Azoles | Inhibit lanosterol 14-α-demethylase (CYP51) → block ergosterol synthesis | Fluconazole, itraconazole, voriconazole, posaconazole, isavuconazole | CYP450 inhibitors (drug interactions); voriconazole: visual disturbances, photosensitivity, hepatotoxicity; fluconazole: no Aspergillus or Mucor coverage |
| Echinocandins | Inhibit beta-(1,3)-D-glucan synthase → disrupt cell wall | Caspofungin, micafungin, anidulafungin | Excellent for Candida (including azole-resistant); no activity against Cryptococcus or Mucor; generally well-tolerated |
| Flucytosine (5-FC) | Converted to 5-FU inside fungal cell → inhibits thymidylate synthase and RNA synthesis | Flucytosine | Used with amphotericin B for cryptococcal meningitis; bone marrow suppression |
| Terbinafine | Inhibits squalene epoxidase | Terbinafine | Dermatophytes (onychomycosis, tinea); hepatotoxicity |
| Griseofulvin | Disrupts mitotic spindle (microtubule function) | Griseofulvin | Dermatophytes only; tinea capitis in children; teratogenic; induces CYP450 |
Antiviral Agents
| Drug | Mechanism | Indication | Key Notes |
|---|---|---|---|
| Acyclovir/valacyclovir | Guanosine analog; phosphorylated by viral thymidine kinase → chain termination of viral DNA polymerase | HSV, VZV | Requires viral TK for activation; dose-adjust in renal impairment; crystalluria |
| Ganciclovir/valganciclovir | Phosphorylated by CMV UL97 kinase → inhibits viral DNA polymerase | CMV | Bone marrow suppression (neutropenia, thrombocytopenia) |
| Foscarnet | Directly inhibits viral DNA polymerase (pyrophosphate analog); does NOT require kinase activation | Acyclovir-resistant HSV, ganciclovir-resistant CMV | Nephrotoxicity, electrolyte abnormalities (hypocalcemia, hypomagnesemia, hypokalemia) |
| Oseltamivir/zanamivir | Neuraminidase inhibitors → block viral release from host cells | Influenza A and B | Most effective within 48 hours of symptom onset; zanamivir is inhaled |
| Sofosbuvir + ledipasvir/velpatasvir | NS5B polymerase inhibitor + NS5A inhibitor (direct-acting antivirals) | HCV (curative in >95%) | Pangenotypic regimens available; 8–12 week courses; check for HBV co-infection (risk of reactivation) |
| Remdesivir | Adenosine nucleotide analog → RdRp inhibitor | COVID-19, RSV, Ebola | IV only; monitor LFTs; shortened hospital stay in COVID-19 |
| Tenofovir/entecavir | Nucleos(t)ide RT inhibitors | Chronic HBV | Viral suppression (not curative); lifelong therapy usually needed |
Antiparasitic Agents
| Drug | Mechanism | Indication |
|---|---|---|
| Chloroquine | Concentrates in parasite food vacuole; inhibits heme polymerization | P. vivax, P. ovale, P. malariae (chloroquine-sensitive areas); P. falciparum in sensitive areas only |
| Artemisinin-based combination therapy (ACT) | Endoperoxide bridge generates free radicals; rapid parasite clearance | P. falciparum malaria (first-line worldwide); severe malaria (IV artesunate) |
| Metronidazole | Free radical DNA damage in anaerobic/microaerophilic organisms | Giardia, Entamoeba, Trichomonas, anaerobic bacteria |
| Ivermectin | Activates glutamate-gated Cl− channels → paralysis | Strongyloides, Onchocerca, scabies (oral), lice |
| Albendazole/mebendazole | Inhibit microtubule polymerization (beta-tubulin) | Broad-spectrum antihelminthic: Ascaris, hookworm, pinworm, whipworm, cysticercosis, hydatid disease |
| Praziquantel | Increases Ca2+ permeability → paralysis and tegumental damage | All trematodes (flukes) and cestodes (tapeworms); schistosomiasis |
| Primaquine/tafenoquine | Generates reactive oxygen species in hypnozoites | P. vivax/ovale radical cure (kills hepatic hypnozoites); check G6PD before use (hemolytic anemia) |
Amphotericin B is the broadest-spectrum antifungal but also the most toxic. The mnemonic "ampho-terrible" captures its side effect profile. Liposomal formulations have significantly reduced nephrotoxicity. It is the drug of choice for severe systemic mycoses, mucormycosis, and induction therapy for cryptococcal meningitis.
Antifungal Spectrum Summary
| Agent | Candida | Aspergillus | Mucor | Cryptococcus | Endemic Mycoses |
|---|---|---|---|---|---|
| Amphotericin B | Yes | Yes | Yes | Yes | Yes |
| Fluconazole | Yes (not C. krusei, variable C. glabrata) | No | No | Yes | Cocci only |
| Voriconazole | Yes | Yes (first-line) | No | Yes | Yes |
| Posaconazole | Yes | Yes | Yes | Yes | Yes |
| Echinocandins | Yes (first-line candidemia) | Yes (salvage) | No | No | No |
Antifungal Coverage Gaps
Fluconazole: No mold coverage (no Aspergillus, no Mucor). Voriconazole: No Mucor coverage (and may actually worsen mucormycosis if used empirically). Echinocandins: No Cryptococcus coverage, no Mucor coverage. Only amphotericin B has activity against Mucor/Rhizopus. When mucormycosis is suspected (DKA + rhinocerebral symptoms), use amphotericin B immediately.
27 Clinical Correlates & Empiric Therapy
Rational antimicrobial prescribing requires matching the most likely pathogen to the clinical syndrome, local resistance patterns, and patient factors (allergies, renal function, immunocompromise).
Empiric Antibiotic Therapy by Syndrome
| Clinical Syndrome | Most Likely Pathogens | Empiric Therapy |
|---|---|---|
| Community-acquired pneumonia (outpatient) | S. pneumoniae, Mycoplasma, Chlamydophila, H. influenzae | Amoxicillin OR doxycycline; azithromycin (if low resistance) |
| Community-acquired pneumonia (inpatient, non-ICU) | Same + Legionella | Beta-lactam (ceftriaxone or ampicillin-sulbactam) + macrolide OR respiratory fluoroquinolone alone |
| Hospital-acquired / ventilator-associated pneumonia | Pseudomonas, MRSA, Acinetobacter, Enterobacterales | Anti-pseudomonal beta-lactam + vancomycin (or linezolid); adjust based on risk factors and local antibiogram |
| Bacterial meningitis (adult) | S. pneumoniae, N. meningitidis | Vancomycin + ceftriaxone + dexamethasone (before or with first antibiotic dose) |
| Bacterial meningitis (neonate) | GBS, E. coli, Listeria | Ampicillin + cefotaxime (or gentamicin) |
| Bacterial meningitis (age >50 or immunocompromised) | S. pneumoniae, N. meningitidis, Listeria, GNR | Vancomycin + ceftriaxone + ampicillin (for Listeria coverage) |
| UTI (uncomplicated cystitis) | E. coli, S. saprophyticus, Klebsiella, Proteus | Nitrofurantoin, TMP-SMX, or fosfomycin |
| Pyelonephritis | E. coli, Klebsiella, Proteus | Fluoroquinolone or ceftriaxone |
| Intra-abdominal infection | Enterobacterales, Bacteroides, Enterococcus | Piperacillin-tazobactam OR meropenem OR ceftriaxone + metronidazole |
| Cellulitis (non-purulent) | S. pyogenes, MSSA | Cefazolin or cephalexin (outpatient) |
| Cellulitis/abscess (purulent, MRSA risk) | MRSA | TMP-SMX or doxycycline (outpatient); vancomycin (inpatient); I&D for abscess |
| Neutropenic fever | Pseudomonas, Enterobacterales, S. aureus | Cefepime or meropenem or piperacillin-tazobactam (monotherapy); add vancomycin if catheter infection suspected |
Culture Interpretation Pearls
| Finding | Interpretation |
|---|---|
| GPC in clusters (blood) | S. aureus until proven otherwise — always pathogenic; full workup required |
| GPC in chains (blood) | Streptococcus or Enterococcus; consider endocarditis, biliary source |
| GPC in pairs (CSF) | S. pneumoniae (lancet-shaped diplococci) |
| GNR in blood | Enteric source (UTI, biliary, intra-abdominal) until proven otherwise |
| GN diplococci in CSF | N. meningitidis; start ceftriaxone + droplet precautions |
| GN diplococci (intracellular) in urethral discharge | N. gonorrhoeae |
| Yeast in blood culture | Always pathogenic; remove lines, ophthalmology consult, echocardiogram; start echinocandin |
Prophylaxis in Special Populations
| Population | Indication | Prophylaxis |
|---|---|---|
| Asplenic patients | Encapsulated organism risk (S. pneumoniae, N. meningitidis, H. influenzae) | Vaccinate (PCV20/PPSV23, MenACWY, MenB, Hib); daily penicillin (children); educate about fever = emergency |
| HIV (CD4 <200) | PCP prevention | TMP-SMX (also covers Toxoplasma) |
| HIV (CD4 <50) | MAC prevention | Azithromycin weekly (if not on effective ART) |
| Transplant recipients | CMV, PCP, Candida | Valganciclovir (CMV), TMP-SMX (PCP), fluconazole (Candida); duration varies by organ and risk |
| Rheumatic fever history | Recurrence prevention | Penicillin V daily or benzathine penicillin G monthly; duration depends on cardiac involvement |
| Prosthetic joint/valve procedures | Endocarditis/surgical site infection | Cefazolin (surgical prophylaxis); amoxicillin before dental procedures (high-risk cardiac conditions) |
| Neutropenia (ANC <500) | Bacterial and fungal infection prevention | Fluoroquinolone prophylaxis (some protocols); antifungal prophylaxis (posaconazole, micafungin) for prolonged neutropenia |
| Close contacts of meningococcal disease | Secondary case prevention | Rifampin, ciprofloxacin, or ceftriaxone (single dose) |
Infection Control Precautions
| Precaution Type | Mechanism | Key Organisms | PPE/Measures |
|---|---|---|---|
| Standard (universal) | All patient care | All | Hand hygiene, gloves (body fluids), gown/mask as needed |
| Contact | Direct/indirect contact with patient or environment | MRSA, VRE, C. difficile, scabies, RSV | Gown + gloves; dedicated equipment; private room preferred |
| Droplet | Large droplets (>5 µm) travel <6 feet | Influenza, N. meningitidis, B. pertussis, mumps, rubella, group A strep (pharyngitis) | Surgical mask within 6 feet; private room |
| Airborne | Small droplet nuclei (<5 µm) remain suspended | TB, measles, varicella/disseminated zoster, smallpox | N95 respirator; negative-pressure room; door closed |
The mnemonic for airborne precautions is "MTV" — Measles, TB, Varicella (chickenpox/disseminated zoster). These require an N95 respirator and a negative-pressure room. C. difficile requires contact precautions with soap and water hand washing (alcohol-based hand sanitizers do NOT kill C. difficile spores).
Antimicrobial Stewardship Principles
De-escalation: Narrow spectrum once culture and susceptibility data are available. Duration: Use the shortest effective course supported by evidence. Biomarkers: Procalcitonin can guide antibiotic discontinuation in respiratory infections and sepsis. IV-to-oral switch: Transition when clinically improving, afebrile, and tolerating oral intake. Antibiogram: Use local resistance data to guide empiric choices.
28 High-Yield Review
Board-relevant and frequently tested topics across medical microbiology, organized for rapid review.
Encapsulated Organisms — "SHiNE SKiS"
Salmonella, Haemophilus influenzae, Neisseria meningitidis, Escherichia coli (K1), Streptococcus pneumoniae, Klebsiella, Group B Strep. Asplenic patients are at extreme risk for infections by encapsulated organisms — the spleen is essential for opsonization and clearance of encapsulated bacteria. Vaccinate asplenic patients against S. pneumoniae, N. meningitidis, and H. influenzae type b.
Organisms by Unique Laboratory Features
| Feature | Organism |
|---|---|
| Quellung reaction (capsular swelling) | S. pneumoniae |
| Satellite colonies around S. aureus (factors X and V) | H. influenzae |
| Chocolate agar with CO2 | N. gonorrhoeae, H. influenzae |
| Charcoal yeast extract (BCYE) agar with iron and cysteine | Legionella |
| Lowenstein–Jensen agar | M. tuberculosis |
| Sabouraud agar (low pH) | Fungi (dermatophytes) |
| Bordet–Gengou agar | B. pertussis |
| Thayer–Martin agar (chocolate + VCN antibiotics) | N. gonorrhoeae, N. meningitidis |
| MacConkey agar (lactose fermenters = pink) | E. coli, Klebsiella (pink); Salmonella, Shigella (colorless) |
| Eosin methylene blue (EMB) agar (green metallic sheen) | E. coli |
| India ink (capsule halo) | Cryptococcus neoformans |
Organisms by Transmission
| Transmission | Organisms |
|---|---|
| Cat exposure | Bartonella henselae (cat scratch disease), Toxoplasma gondii (feces), Pasteurella (bite) |
| Dog bite | Pasteurella multocida, Capnocytophaga canimorsus (fulminant sepsis in asplenic patients) |
| Tick bite | Lyme, RMSF, ehrlichiosis, anaplasmosis, babesiosis, tularemia |
| Pigeon/bat droppings | Cryptococcus, Histoplasma |
| Contaminated water | Legionella (cooling towers), Pseudomonas (hot tubs), Naegleria (warm freshwater) |
| Unpasteurized dairy | Listeria, Brucella, Campylobacter |
| Rose thorn/gardening | Sporothrix schenckii |
| Undercooked pork | Trichinella, Taenia solium, Yersinia |
| Undercooked chicken/eggs | Salmonella, Campylobacter |
Rapid-Fire High-Yield Associations
| Association | Answer |
|---|---|
| Most common cause of UTI | E. coli |
| Most common cause of community-acquired pneumonia | S. pneumoniae |
| Most common cause of meningitis in neonates | GBS (S. agalactiae) > E. coli > Listeria |
| Most common cause of osteomyelitis | S. aureus (all ages); Salmonella in sickle cell disease |
| Most common cause of bacterial gastroenteritis (US) | Campylobacter jejuni > Salmonella |
| Rusty sputum | S. pneumoniae |
| Currant jelly sputum | Klebsiella |
| Rice-water stool | V. cholerae |
| Red currant jelly stool | EHEC or intussusception |
| Owl-eye inclusion bodies | CMV |
| Negri bodies (eosinophilic intracytoplasmic inclusions) | Rabies |
| Cowdry type A inclusions (intranuclear) | HSV, VZV |
| Auer rods | AML (not microbiology, but frequently confused with microbiologic inclusions) |
| Guillan-Barré syndrome association | Campylobacter jejuni (molecular mimicry with ganglioside GM1) |
| Reactive arthritis (Reiter syndrome) | Chlamydia, Salmonella, Shigella, Campylobacter, Yersinia |
The most common cause of sepsis is Gram-negative bacteria (E. coli #1), but S. aureus is the most common Gram-positive cause of bacteremia. Always send 2 sets of blood cultures (4 bottles) from 2 separate sites BEFORE starting antibiotics. A single positive blood culture for S. aureus or Candida is NEVER a contaminant.
Organisms That Do Not Gram Stain Well
| Organism | Reason | Alternative Stain/Method |
|---|---|---|
| Mycobacterium | Mycolic acid-rich cell wall resists crystal violet penetration | Acid-fast stain (Ziehl–Neelsen: red; Kinyoun: cold acid-fast) |
| Mycoplasma | No cell wall (no peptidoglycan) | Culture on Eaton agar; serology; PCR |
| Treponema | Too thin for light microscopy resolution | Darkfield microscopy; silver stain (Warthin–Starry); serology (RPR/VDRL, FTA-ABS) |
| Chlamydia | Obligate intracellular; too small | Giemsa stain (inclusions); DFA; NAAT (gold standard) |
| Rickettsia | Obligate intracellular; too small | Giemsa stain; serology (IFA); PCR |
| Legionella | Stains poorly on Gram stain | Silver stain (Dieterle); culture on BCYE agar; urinary antigen |
Congenital (TORCH) Infections
| Pathogen | Transmission | Key Findings in Newborn |
|---|---|---|
| Toxoplasma gondii | Transplacental | Chorioretinitis, hydrocephalus, diffuse intracranial calcifications, seizures |
| Other (syphilis, VZV, parvovirus B19) | Transplacental | Syphilis: rhinitis (snuffles), rash, osteochondritis, Hutchinson teeth, saddle nose. Parvovirus: hydrops fetalis |
| Rubella | Transplacental | Sensorineural deafness (#1 finding), cataracts, PDA (heart defect), blueberry muffin rash |
| CMV | Transplacental (#1 congenital infection) | Sensorineural hearing loss (#1 infectious cause), periventricular calcifications, hepatosplenomegaly, petechiae, microcephaly |
| HSV | Birth canal (intrapartum) | Skin vesicles, encephalitis, disseminated disease; C-section indicated if active lesions at delivery |
CMV is the most common congenital infection and the most common infectious cause of sensorineural hearing loss in children. Periventricular calcifications (CMV) are distinguished from diffuse/scattered calcifications (Toxoplasma). Most congenital CMV cases are asymptomatic at birth but may develop hearing loss later.
Bioterrorism Category A Agents
| Agent | Disease | Key Features |
|---|---|---|
| Bacillus anthracis | Anthrax | Inhalational anthrax: widened mediastinum on CXR; cutaneous: painless black eschar |
| Yersinia pestis | Plague | Bubonic (painful inguinal lymphadenopathy/buboes), pneumonic (person-to-person), septicemic |
| Francisella tularensis | Tularemia | Ulceroglandular most common form; very low infectious dose |
| Clostridium botulinum toxin | Botulism | Descending flaccid paralysis; bioweapon via aerosolized toxin |
| Variola major | Smallpox | Synchronous vesiculopustular rash (all lesions at same stage); eradicated 1980 |
| Ebola / Marburg viruses | Viral hemorrhagic fever | High case-fatality rate; person-to-person via body fluids |
Vaccine-Preventable Infections
| Vaccine | Type | Target Organism |
|---|---|---|
| DTaP/Tdap | Toxoid (diphtheria, tetanus) + acellular pertussis | C. diphtheriae, C. tetani, B. pertussis |
| MMR | Live attenuated | Measles, mumps, rubella |
| Varicella / Shingrix | Live attenuated (varicella) / recombinant adjuvanted (Shingrix) | VZV |
| PCV20, PPSV23 | Conjugate / polysaccharide | S. pneumoniae |
| MenACWY, MenB | Conjugate / recombinant | N. meningitidis |
| Hib | Conjugate (PRP-protein) | H. influenzae type b |
| HPV (Gardasil-9) | Recombinant VLP | HPV types 6, 11, 16, 18, 31, 33, 45, 52, 58 |
| HBV | Recombinant (HBsAg) | Hepatitis B |
| Influenza | Inactivated or live attenuated (nasal) | Influenza A and B |
| Rotavirus | Live oral | Rotavirus |
Exam Focus: Key high-yield topics: (1) Toxin mechanisms (especially A-B toxins and superantigens); (2) Gram stain morphology → organism identification; (3) Antibiotic mechanisms and resistance; (4) Empiric therapy by syndrome; (5) HIV opportunistic infections by CD4 count; (6) Hepatitis B serology interpretation; (7) Endemic mycoses by geography; (8) Parasite life cycles and treatment; (9) ESKAPE pathogens and resistance mechanisms; (10) Vaccine-preventable diseases; (11) TORCH infections and congenital findings; (12) Organisms that do not Gram stain and their alternative diagnostic methods.