Core Science

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 (PrP^Sc); 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 PrP^C to the misfolded PrP^Sc 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 G_s → permanently activates adenylyl cyclase → ↑cAMP → secretory diarrhea	Rice-water diarrhea
Heat-labile toxin (LT)	ETEC	ADP-ribosylates G_s → ↑cAMP (like cholera toxin)	Traveler's diarrhea
Pertussis toxin	B. pertussis	ADP-ribosylates G_i → ↑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 G_s (↑cAMP); pertussis targets G_i (↑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.