StepWise USMLE
Medical Microbiology Β· Bacteriology

Bacterial Pathogens & Normal Flora

IdentificationVirulenceDiseaseTherapy

Concept

  • Resident microbes live on surfaces open to the outside world
  • Composition is semi-permanent
    • Shifts with major life events (birth, diet, antibiotics, aging)
  • Internal sterile sites
    • Blood
    • Internal organs
    • Stomach (acid-sterilized)

Site-by-Site Residents

SiteDominantOther notable
Skin, outer ear, distal urethraS. epidermidisS. aureus, diphtheroids, streptococci, yeasts (Candida)
Anterior naresS. aureusS. epidermidis, diphtheroids
OropharynxViridans streptococci (incl. S. mutans)Non-pathogenic Neisseria, unencapsulated H. influenzae, C. albicans
Gingival crevicesOral anaerobesPrevotella, Fusobacterium, Actinomyces, Bacteroides
Colon (adult)Bacteroides/Prevotella (anaerobes outnumber all)E. coli, Bifidobacterium, Enterococcus faecalis, Eubacterium
Colon (breast-fed infant)BifidobacteriumLactobacillus, streptococci
VaginaLactobacillusStreptococci, Gram-negative rods, yeasts, Veillonella

Helpful Roles

  • Barrier effect
    • Occupy attachment sites
    • Consume local nutrients
  • Chemical defense
    • Keep local pH unfavorable to invaders
  • Nutrition
    • Make vitamin K
    • Make B-complex vitamins

Harmful Roles (Endogenous Disease)

  • Right organism, wrong place
    • Fecal flora β†’ urinary tract
    • Skin flora β†’ catheter/prosthesis
  • Host defenses fall
    • Overgrowth, e.g., oral candidiasis (thrush)
  • Vaginal group B strep colonization occurs in about 15–20% of women.
  • Passage through the birth canal can seed neonatal sepsis or meningitis.
  • E. coli from fecal flora can do the same.
  • S. mutans makes a sticky glucan biofilm that cements oral bacteria to enamel (plaque).

Terminology

TermMeaning
BacteremiaBacteria in blood, no overt illness
SepticemiaBacteria multiplying in blood with symptoms
Endogenous infectionCaused by the host's own flora
Exogenous infectionAcquired from environment, person, animal, or food
Family namesEnd in "-aceae"
Genus/speciesItalicized; genus may be abbreviated
ClassBehaviorExamples
Obligate aerobe
  • Needs Oβ‚‚ for respiration
  • No fermentation
  • Usually has superoxide dismutase
Mycobacterium, Pseudomonas, Bacillus
Microaerophile
  • Grows only at reduced Oβ‚‚ tension
Campylobacter, Helicobacter
Facultative anaerobe
  • Respires aerobically while Oβ‚‚ lasts
  • Ferments when Oβ‚‚ runs out
Most bacteria, e.g., Enterobacteriaceae
Obligate anaerobe
  • Lacks superoxide dismutase
  • Usually lacks catalase
  • Ferments only
  • Oβ‚‚ cannot be the final electron acceptor
Actinomyces, Bacteroides, Clostridium

Why Oxygen Kills Anaerobes

O₂ reduced→Superoxide / peroxide→No SOD / catalase→Oxidative cell damage
  • Anaerobes thrive in dead, poorly perfused tissue.
  • Aminoglycosides work poorly against anaerobes because uptake needs oxygen-dependent transport.

Gram Stain Sequence

1 · Crystal violet→ 2 · Iodine (mordant)→ 3 · Alcohol/acetone wash→ 4 · Safranin counterstain
StepGram-positiveGram-negative
Crystal violetPurplePurple
IodinePurple (large complex trapped)Purple (complex forms)
DecolorizerStays purpleLoses color
SafraninPurplePink-red

Structural Basis

  • Gram-positive
    • Thick peptidoglycan
    • Dehydrates with alcohol, locks dye complex in
  • Gram-negative
    • Thin peptidoglycan plus outer membrane
    • Alcohol dissolves outer membrane, dye escapes

Rules That Save Time

  • Nearly all cocci are Gram-positive
    • Exceptions: Neisseria, Moraxella, Veillonella
  • Every spore-former is Gram-positive (Bacillus, Clostridium)
  • Tissue-modified Gram stains give a pale red background

Acid-Fast Stain (Ziehl–Neelsen / Kinyoun)

StepAcid-fastNon-acid-fast
Carbol fuchsin (+ heat in ZN)RedRed
Acid-alcohol washStays redColorless
Methylene blueRedBlue
  • Heat drives dye through the waxy mycolic-acid wall
  • Acid-fast organisms
    • Mycobacterium (fully)
    • Nocardia (partially, weak acid-fast)
    • Protozoan oocysts: Cryptosporidium, Cystoisospora, Cyclospora
  • Background cells and sputum stain blue

Organisms That Stain Poorly or Not at All

GroupReasonWall type
MycobacteriumWaxy wall repels dyeGram-positive
SpirochetesToo thin to see colorGram-negative
ChlamydiaeTiny, intracellularGram-negative
RickettsiaeTiny, intracellularGram-negative
LegionellaFaint unless counterstain is prolongedGram-negative
MycoplasmaNo cell wall at allNone

Gram-Positive

ShapeGenera
CocciStaphylococcus, Streptococcus, Enterococcus
Rods, aerobic/facultativeBacillus, Listeria, Corynebacterium, Nocardia, Mycobacterium
Rods, anaerobicActinomyces, Clostridium, Cutibacterium, Lactobacillus

Gram-Negative

Shape / groupGenera
CocciNeisseria, Moraxella
Non-enteric rodsPseudomonas, Burkholderia, Acinetobacter, Eikenella, Kingella, Haemophilus, Bartonella, Legionella, Brucella, Bordetella, Francisella, Capnocytophaga, Pasteurella
Curved / helicalCampylobacter, Helicobacter, Vibrio
EnterobacteriaceaeEscherichia, Shigella, Salmonella, Klebsiella, Proteus, Yersinia, Serratia, Citrobacter, Enterobacter (plus Aeromonas listed alongside)
Anaerobic rodsBacteroides, Prevotella, Porphyromonas, Fusobacterium
Gram-variable rodsGardnerella, Mobiluncus
SpirochetesTreponema, Borrelia, Leptospira

Do Not Gram-Stain Well

FamilyGenera
MycoplasmataceaeMycoplasma, Ureaplasma
RickettsiaceaeRickettsia, Ehrlichia, Coxiella
ChlamydiaceaeChlamydia, Chlamydophila
  • Obligate intracellular or wall-less organisms need non-Gram methods (serology, PCR, special culture).

Decision Pathway

Gram+ coccus→ catalase test
Catalase +→Staphylococcus→ coagulase
Coagulase + β†’ S. aureus
Coagulase βˆ’ β†’ CoNSβ†’ novobiocinSensitive β†’ S. epidermidisResistant β†’ S. saprophyticus
Catalase βˆ’β†’Strep / Enterococcusβ†’ hemolysis pattern
Ξ² (clear)β†’ bacitracinSensitive β†’ S. pyogenesResistant β†’ S. agalactiae
Ξ± (green)β†’ optochin / bileSensitive, soluble β†’ S. pneumoniaeResistant, insoluble β†’ viridans
Ξ³ (none)β†’Enterococcus (bile-esculin +)

Comparison of Key Species

SpeciesCatalaseCoagulaseHemolysisLab discriminators
S. aureus++Ξ²Ferments mannitol; salt-tolerant; golden colonies
S. epidermidis+βˆ’noneNovobiocin-S; biofilm former
S. saprophyticus+βˆ’noneNovobiocin-R
S. pyogenes (GAS)βˆ’βˆ’Ξ²Bacitracin-S; PYR +
S. agalactiae (GBS)βˆ’βˆ’Ξ²Bacitracin-R; CAMP +; hippurate +
S. pneumoniaeβˆ’βˆ’Ξ±Optochin-S; bile-soluble
Viridans groupβˆ’βˆ’Ξ±Optochin-R; bile-insoluble; PYR βˆ’
Enterococcusβˆ’βˆ’variable / Ξ³PYR +; grows in bile and 6.5% NaCl

Hemolysis key

  • Ξ² = complete clearing around colony
  • Ξ± = partial, greenish discoloration
  • Ξ³ = no hemolysis
  • Staph and strep cause overlapping diseases (skin infection, endocarditis), so lab discriminators decide the answer.
  • Staph appear in clusters; strep and enterococci appear in chains or pairs.

Genus Profile

  • Gram-positive cocci in grape-like clusters
  • Catalase-positive
  • Medically relevant species
    • S. aureus
    • S. epidermidis
    • S. saprophyticus

S. aureus

Identification

  • Golden colonies on blood agar
  • Ξ²-hemolytic
  • Coagulase-positive (only staph that is)
  • Ferments mannitol on mannitol-salt agar

Reservoir

  • Skin
  • Anterior nares (about 25% carriers)

Transmission

  • Hand contact
  • Respiratory droplets
  • Surgical wounds
  • Food contaminated by handlers (custard pastries, potato salad, cured meats)

Risk Factors

  • Surgery or open wounds
  • Foreign material (tampons, packing, sutures)
  • Severe neutropenia (ANC <500/Β΅L)
  • Injection drug use
  • Chronic granulomatous disease
  • Cystic fibrosis

Virulence Factors

FactorAction
Protein ABinds Fc of IgG β†’ blocks opsonization/phagocytosis
CoagulaseConverts fibrinogen β†’ fibrin; walls off lesions
EnterotoxinsHeat-stable; preformed in food; act rapidly
TSST-1Superantigen β†’ polyclonal T-cell activation β†’ cytokine storm
ExfoliatinsCleave epidermal adhesion proteins β†’ skin peeling, bullae
Ξ±-toxin / Panton–Valentine leukocidinPore-forming cytolysins; PVL is phage-encoded and tied to severe MRSA

Disease Spectrum

DiseaseKey featuresDriver
Food poisoning
  • Onset 2–6 h after eating
  • Nausea, cramps, vomiting, then diarrhea
  • Short, self-limited
Preformed enterotoxins
Acute endocarditis
  • High fever, leukocytosis
  • Murmur may be absent early
  • Common in injection drug use
Fibrin-platelet vegetation, cytolysins
Abscess, mastitis
  • Hot, tender, fluctuant mass
Coagulase, cytolysins
Toxic shock syndrome
  • Fever, hypotension
  • Diffuse sunburn-like rash
  • Later desquamation of palms/soles
  • Multiorgan failure
TSST-1
Impetigo (bullous)
  • Papules β†’ blisters
Exfoliatins
Scalded skin syndrome
  • Diffuse epidermal sloughing
  • Mainly infants
Exfoliatins
Pneumonia
  • Rapid, necrotizing
  • Post-influenza, ventilator, IV drug use, CF, CGD
Cytolysins, coagulase
Osteomyelitis
  • Bone pain, fever, swelling
  • Lytic lesions on imaging
  • Most common cause overall
Cytolysins
Septic arthritis
  • Hot, painful single joint
Cytolysins
Surgical-site infection
  • Cellulitis Β± abscess with fever
Coagulase, exfoliatins Β± TSST
  • Osteomyelitis: S. aureus is the default; sickle cell disease shifts the answer to Salmonella.
  • Staph enterotoxin food poisoning has no fever-driven invasion; the toxin is already in the food.
  • Toxin-mediated syndromes (TSS, SSSS) can occur with a tiny, localized infection.

Treatment

SituationChoice
Methicillin-susceptible (MSSA)Nafcillin or oxacillin (penicillinase-resistant)
MRSAVancomycin
VISA / VRSAQuinupristin–dalfopristin, among other alternatives
Topical / nasal decolonizationMupirocin
Food poisoningSupportive only

Coagulase-Negative Species

FeatureS. epidermidisS. saprophyticus
NovobiocinSensitiveResistant
HabitatSkinGenitourinary tract
Key traitBiofilm on plasticAdheres to urothelium
Disease
  • Catheter, shunt, prosthetic-valve and joint infections
  • Endocarditis in IV drug users
  • Cystitis in young, newly sexually active women
  • A blood culture with a single coag-negative staph is often a contaminant.
  • Prosthetic material plus coag-negative staph points to S. epidermidis.

Genus Profile

  • Gram-positive cocci in chains or pairs
  • Catalase-negative
  • Lancefield grouping uses cell-wall carbohydrate antigens (groups A–O)
  • Exceptions to grouping
    • S. pneumoniae is typed by capsule
    • Viridans streptococci are not groupable
  • GAS subtyped by M protein

Group A: S. pyogenes

Identification

  • Ξ²-hemolytic
  • Bacitracin-sensitive
  • PYR-positive

Reservoir / spread

  • Human throat and skin
  • Droplets and direct contact

Virulence

  • Hyaluronic acid capsule
    • Poorly immunogenic (self-mimicry)
  • M protein
    • Antiphagocytic
    • Linked to rheumatic fever and glomerulonephritis
  • Streptolysin O (immunogenic, oxygen-labile)
  • Streptolysin S (non-immunogenic, oxygen-stable)

Spreading enzymes

FactorEffect
StreptokinaseDissolves fibrin clots
DNaseThins pus, helps lesion extension
HyaluronidaseBreaks down connective-tissue matrix
Pyrogenic (erythrogenic) exotoxins A–CPhage-encoded superantigens β†’ fever and scarlet fever rash

GAS Disease Map

CategoryEntityFeatures
SuppurativePharyngitisSudden sore throat, fever, headache, tonsillar exudate, tender anterior cervical nodes
Scarlet feverPharyngitis plus fine blanching sandpaper rash, circumoral pallor, strawberry tongue; palms/soles usually spared
Impetigo / pyodermaHoney-colored crusted skin lesions
Other invasiveCellulitis, erysipelas, necrotizing fasciitis, lymphangitis, puerperal sepsisRapid spread via spreading enzymes
Non-suppurativeRheumatic fever
  • Follows pharyngitis by about 2 weeks
  • Fever, migratory polyarthritis, carditis, erythema marginatum, chorea (later)
  • Type II hypersensitivity (molecular mimicry with heart tissue)
Post-strep glomerulonephritis
  • After throat or skin infection
  • Edema, hypertension, smoky/cola urine
  • Type III hypersensitivity (immune complexes)

Diagnosis

  • Rapid antigen test misses roughly 25% β†’ culture negatives
  • ASO titer above ~200 IU supports rheumatic fever
  • Anti-DNase B and anti-hyaluronidase titers support glomerulonephritis (skin-source too)

Management

  • Treatment: Ξ²-lactam; macrolide if penicillin-allergic
  • Prevention: prolonged antibiotic prophylaxis (at least 5 years) after rheumatic fever
  • Treating strep throat prevents rheumatic fever but does not reliably prevent glomerulonephritis.
  • Skin-source GAS gives glomerulonephritis but not rheumatic fever.

Group B: S. agalactiae

Identification

  • Ξ²-hemolytic
  • Bacitracin-resistant
  • Hippurate hydrolysis +
  • CAMP test +
    • CAMP factor enhances S. aureus hemolysis
    • Gives an arrowhead-shaped zone

Reservoir

  • Vagina (15–20% of women)
  • Lower GI tract

Pathogenesis / disease

  • Capsule, Ξ²-hemolysin, CAMP factor
  • Passed to newborn during delivery
    • Higher risk with prolonged membrane rupture
  • Leading cause of neonatal sepsis and meningitis
  • Treatment: penicillin or ampicillin (Β± aminoglycoside or cephalosporin initially in neonates)
  • Prevention
    • Intrapartum prophylaxis if vaginal/rectal culture positive
    • Also for prior GBS-affected infant or prolonged rupture

S. pneumoniae

Identification

  • Ξ±-hemolytic
  • Lancet-shaped diplococci
  • Optochin-sensitive
  • Bile-soluble
  • Quellung reaction: capsule swells with type-specific antiserum

Reservoir

  • Upper respiratory tract (nasopharyngeal carriage)
  • Droplet spread; not highly contagious

Risk factors

  • Recent influenza or measles
  • COPD
  • Heart failure
  • Alcoholism
  • Asplenia (overwhelming sepsis)

Virulence

  • Polysaccharide capsule (dominant)
  • IgA protease
  • Teichoic acid, peptidoglycan (CNS inflammation)
  • Pneumolysin: injures epithelium, blunts burst and complement

Diseases

DiseaseDetails
Lobar pneumoniaMost common cause of community pneumonia; shaking chills, high fever, lobar consolidation, rusty blood-tinged sputum
MeningitisMost common adult cause; CSF: neutrophils ↑, glucose ↓, protein ↑
Otitis media / sinusitisMost common bacterial cause in children
Sepsis in aspleniaEncapsulated organism not cleared without spleen

Diagnosis

  • Gram stain and culture of sputum or CSF
  • Urinary antigen test
  • Latex agglutination for capsular antigen in CSF

Treatment

  • Pneumonia: Ξ²-lactam
  • Meningitis: ceftriaxone or cefotaxime plus vancomycin if resistance is common locally
  • Otitis/sinusitis (children): amoxicillin

Prevention

  • Immunity is serotype-specific (>80 capsule types)
  • Conjugate vaccine (children)
    • 13-valent in the older formulation
    • Protein-conjugated β†’ T-cell help β†’ strong infant response
  • Polysaccharide vaccine (adults)
    • 23 serotypes
    • Given at β‰₯65 y and to at-risk groups

Viridans Streptococci

Identification

  • Ξ±-hemolytic
  • Optochin-resistant
  • Bile-insoluble
  • PYR-negative

Members

  • S. mutans, S. sanguinis (mouth)
  • S. gallolyticus (formerly S. bovis; colon)

Pathogenesis

  • Dextran/glucan biofilm sticks to enamel
  • Same sticky matrix glues to damaged valves and forms vegetations
  • Vegetation shields bacteria from immune clearance
  • Source is endogenous
DiseaseDetails
Dental cariesS. mutans plaque; acid from sugar fermentation erodes enamel
Subacute endocarditisAbnormal or prosthetic valve + bacteremia after dental work; fatigue, low fever, night sweats, weight loss, splinter hemorrhages
S. gallolyticus bacteremiaPrompt colonoscopy to look for colon cancer
  • Treatment: penicillin G (Β± aminoglycoside) for endocarditis
  • Prevention: antibiotic prophylaxis before dental procedures in high-risk valve patients
  • Acute valve infection with rapid destruction β†’ S. aureus.
  • Subacute course on a diseased valve after dental work β†’ viridans strep.
  • Elderly man with endocarditis after GU/GI procedure β†’ Enterococcus.

Features

  • E. faecalis and E. faecium
  • Group D Gram-positive cocci, pairs/short chains
  • Catalase-negative
  • PYR-positive
  • Variable hemolysis
  • Hydrolyze esculin with 40% bile β†’ black bile-esculin agar
  • Grow in 6.5% NaCl

Ecology

  • Colon, sometimes urethra and female genital tract
  • Endogenous spread
  • Bile and salt tolerance β†’ survive in gut and biliary tree

Pathogenesis Chain

GI/GU instrumentation→Bacteremia→Previously damaged valve→Subacute endocarditis

Diseases

  • Urinary tract infection
  • Biliary tract infection
  • Subacute endocarditis (often older adults with valve damage)

Therapy & Resistance

  • Intrinsically resistant to many drugs
    • Cephalosporins are ineffective
  • Low-level resistance β†’ ampicillin Β± gentamicin or streptomycin (synergy)
  • Vancomycin-resistant enterococci (VRE)
    • No dependable first-line option in some strains
  • VanA mechanism
    • Cell-wall precursor terminal D-Ala-D-Ala is swapped for D-Ala-D-lactate
    • Precursor still builds wall but vancomycin cannot bind
  • Prevention: prophylaxis (penicillin + gentamicin) before GI/GU manipulation in high-risk valve patients
  • Bile-esculin positive plus salt-tolerant separates enterococci from non-enterococcal group D strep.
  • Penicillin alone is not reliably bactericidal for enterococcal endocarditis.
GenusSporesAerobic growthExotoxin diseaseFacultative intracellularAcid-fastBranching
Bacillus+++βˆ’βˆ’βˆ’
Clostridium+βˆ’ (anaerobe)+βˆ’βˆ’βˆ’
Listeriaβˆ’+βˆ’+βˆ’βˆ’
Corynebacteriumβˆ’++βˆ’βˆ’βˆ’
Actinomycesβˆ’βˆ’ (anaerobe)βˆ’βˆ’βˆ’+
Nocardiaβˆ’+βˆ’βˆ’partial+
Mycobacteriumβˆ’+βˆ’++βˆ’
  • Only Bacillus and Clostridium form spores.
  • Branching filamentous rods: Actinomyces (anaerobic, not acid-fast) versus Nocardia (aerobic, partially acid-fast).
  • Gram-positive rods that make toxins: Bacillus, Clostridium, Corynebacterium.

B. anthracis

Features

  • Large, square-ended (boxcar) Gram-positive rods
  • Spore-forming, aerobic
  • Capsule is poly-D-glutamic acid (a polypeptide)
  • Bioterrorism concern

Source and spread

  • Reservoir: livestock, hides, wool, soil
  • Contact with infected animal products
  • Inhaled spores (occupational or deliberate release)

Anthrax Toxin Components

ComponentRole
Protective antigen (PA)Binding/translocation unit; delivers LF and EF into cells
Lethal factor (LF)Zinc protease; kills cells
Edema factor (EF)Calmodulin-activated adenylate cyclase β†’ ↑cAMP β†’ edema
  • Capsule is antiphagocytic

Clinical Forms

FormCourse
CutaneousPapule β†’ vesicle β†’ painless black eschar with surrounding edema; regional nodes; best prognosis
Inhalational (woolsorter's)Flu-like start β†’ abrupt respiratory failure, hemorrhagic mediastinitis, shock; high mortality
Gastrointestinal (rare)Vomiting, bloody diarrhea, GI obstruction
  • Diagnosis
    • Widened mediastinum on chest X-ray
    • Gram stain/culture of blood, lesion, or secretions
    • PCR, serology
  • Treatment: ciprofloxacin or doxycycline
    • Resistance genes to some agents have been engineered or transferred
  • Prevention
    • Acellular toxoid-based vaccine for high-risk groups
    • Raxibacumab for prophylaxis/treatment (anti-PA antibody)

B. cereus

  • Spore-forming; found widely in the environment
  • Food-borne intoxication
    • Linked to starchy foods held warm (reheated fried rice, buffets)
  • Eye infection after trauma (rare)
SyndromeToxinTimingPicture
EmeticPreformed, heat-stable1–6 hVomiting predominates (resembles staph food poisoning)
DiarrhealMade in the gut; heat-labile, ↑cAMP8–18 hWatery, nonbloody diarrhea (resembles ETEC)
  • Diagnosis: clinical; culture of implicated food
  • Treatment: supportive; vancomycin for ocular infection

Overview

  • Anaerobic, Gram-positive, spore-forming rods
  • Pathogens
    • C. tetani
    • C. botulinum
    • C. perfringens
    • C. septicum
    • C. difficile (now Clostridioides)
  • Most disease is toxin-driven

C. tetani

Source

  • Soil reservoir
  • Puncture wounds, crush injuries, burns, bites
  • Needs low tissue oxygen to germinate

Toxin pathway

Spores germinateβ†’Tetanospasminβ†’Retrograde axonal transportβ†’Spinal inhibitory neurons→↓ glycine/GABA release

Result

  • Motor neurons fire unopposed
  • Spastic paralysis
  • Trismus (lockjaw)
  • Risus sardonicus
  • Opisthotonos
  • Painful generalized spasms
  • Diagnosis: clinical; organism seldom cultured
  • Treatment
    • Human tetanus immune globulin
    • Metronidazole (or penicillin)
    • Benzodiazepines for spasm
    • Wound debridement; delay closure
    • Airway support
  • Prevention
    • Toxoid vaccine (formalin-inactivated toxin)
    • Wound care (disinfectants do not kill spores)

Wound Prophylaxis Matrix

Vaccination historyClean, minor woundDirty / tetanus-prone wound
Primary series incomplete or unknownVaccineVaccine + immune globulin
Primary series completeBooster if >10 y since lastBooster if >5 y since last
  • Tetanus-prone features
    • Burns, frostbite, crush or missile injuries
    • Devitalized tissue
    • Soil, feces, saliva contamination
    • Wound older than ~6 h or deeper than ~1 cm

C. botulinum

  • Soil and dust spores
  • Germinate in warm, low-acid, anaerobic, nutrient-rich conditions
  • Toxin
    • A–B polypeptide neurotoxin; types A, B (and E) most often cause human disease
    • Phage-encoded
    • Heat-labile (inactivated by boiling food)
    • Absorbed β†’ blood β†’ peripheral cholinergic nerve endings
    • Blocks acetylcholine release (cleaves SNARE proteins)
    • Flaccid, descending paralysis
FeatureAdult / foodborneInfant
AcquisitionPreformed toxin in poorly processed canned low-acid foodSpores ingested (honey, dust) β†’ colonize gut β†’ toxin made in vivo
PresentationBlurred vision, diplopia, dysphagia, dizziness, weakness, constipation within 1–2 daysConstipation, weak suck and cry, hypotonia (floppy), may progress to respiratory failure
Toxin found inSuspect food (also serum)Stool, serum
TreatmentVentilatory support; antitoxinIntensive supportive care; human-derived botulism immune globulin; avoid antibiotics
PreventionProper canning; heating home-canned foodsNo honey before age 1 year
  • Tetanus gives spastic paralysis; botulism gives flaccid paralysis.
  • Botulism is afebrile with clear mental status and descending weakness.

C. perfringens

Features

  • Large, nonmotile rods; spores uncommon in tissue
  • Rapid fermentation (gas) in milk medium
  • Double zone of hemolysis on blood agar
  • Reservoir: soil and human colon

Toxins

  • Ξ±-toxin (phospholipase C / lecithinase)
    • Destroys cell membranes (RBC, WBC, platelets, endothelium)
    • Drives hemolysis and tissue necrosis
    • Nagler reaction: lecithinase halo on egg-yolk agar is blocked by antitoxin
  • Many additional tissue-damaging toxins
  • Enterotoxin (gut) β†’ ion transport disruption β†’ watery diarrhea
DiseaseDetails
Gas gangrene (myonecrosis)
  • Soil- or fecal-contaminated wound
  • Severe, escalating pain
  • Tense swollen tissue, crepitus, exudate
  • Fever, tachycardia out of proportion, sweating, pallor
  • Rapid progression, high mortality
Food poisoning
  • Reheated meats or gravies
  • 8–24 h after eating
  • Watery, noninflammatory diarrhea with cramps
  • Resolves in about a day
  • Diagnosis: clinical (imaging may show tissue gas)
  • Treatment: urgent surgical debridement; penicillin + clindamycin; hyperbaric oxygen as adjunct
  • Prevention: thorough debridement and prophylaxis in dirty wounds

C. septicum

  • Anaerobic Gram-positive rod
  • Endogenous origin
  • Spontaneous gangrene/sepsis in patients with colon cancer

C. difficile

  • Colon is the reservoir; endogenous or hospital/nursing-home spread
  • Toxins
    • Toxin A: enterotoxin β†’ mucosal damage, fluid secretion, neutrophil recruitment
    • Toxin B: cytotoxin β†’ cytopathic cell injury
  • Trigger: antibiotic disruption of normal flora
    • Classic culprits: clindamycin, cephalosporins, ampicillin/amoxicillin, fluoroquinolones
  • Disease
    • Diarrhea, colitis
    • Pseudomembranous colitis (yellow-white plaques on colonoscopy)
  • Diagnosis
    • Stool toxin or toxin-gene detection
    • Culture alone is not diagnostic (organism can colonize)
  • Treatment
    • Stop the inciting antibiotic when possible
    • Oral vancomycin or fidaxomicin; metronidazole in selected cases
    • Fecal microbiota transplant for recurrent disease
  • Prevention
    • Restrict broad-spectrum antibiotics
    • Isolate symptomatic patients, contact precautions
    • Soap-and-water handwashing (alcohol gel does not kill spores)
    • Sporicidal environmental cleaning
ClueThink
Foul vomiting 2–6 h after custard or potato saladS. aureus enterotoxin
Fever, hypotension, palm/sole peeling, tamponTSST-1 (S. aureus)
Catheter or prosthetic device infection, novobiocin-SS. epidermidis
Young sexually active woman, cystitis, novobiocin-RS. saprophyticus
Sore throat then joint pain and carditisGAS β†’ rheumatic fever
Cola-colored urine, edema after skin or throat infectionGAS β†’ glomerulonephritis
Newborn sepsis/meningitis, CAMP +GBS
Rusty sputum, lobar consolidation, optochin-SS. pneumoniae
Dental procedure then subacute valve infectionViridans streptococci
Endocarditis after urinary/GI procedure in older manEnterococcus
Black eschar or widened mediastinumB. anthracis
Vomiting within hours of reheated fried riceB. cereus (emetic)
Dirty wound, lockjaw, spasmsC. tetani
Home-canned vegetables, descending flaccid paralysis; infant with honeyC. botulinum
Crepitus, severe pain, necrotic woundC. perfringens
Diarrhea after antibiotics, pseudomembranesC. difficile
  • Catalase separates staph (+) from strep/enterococci (βˆ’).
  • Coagulase separates S. aureus from other staph.
  • Bacitracin separates GAS (S) from GBS (R).
  • Optochin and bile solubility separate pneumococcus from viridans.
  • Toxins explain most of the clostridial syndromes; spores explain why disinfectants fail.