Gram-positiveBacilliNon-spore-forming

Corynebacterium diphtheriae

Gram-positive, non-spore-forming, club-shaped bacillus that produces a potent exotoxin causing diphtheria, characterized by a pharyngeal pseudomembrane and systemic toxin-mediated myocarditis and neuropathy.

Organism Card

DomainMust know
Identity
  • G+ve club-shaped (coryneform) bacillus; non-spore-forming, non-motile [1]
  • Arranged in "Chinese-letter" / palisade pattern on Gram stain
  • Aerobic/facultatively anaerobic; unencapsulated
  • Three biotypes: gravis, mitis, intermedius (gravis historically most severe)
Lab discriminator
  • Grows on Löffler's coagulated serum medium (enhances metachromatic granules) [1]
  • Tellurite agar → black/grey colonies (selective medium) [1]
  • Metachromatic (volutin) granules seen with Albert stain or methylene blue [1]
  • Catalase +ve; urease −ve (vs C. urealyticum urease +ve)
  • Elek test (immunodiffusion) = gold standard to detect toxin production [1]
  • Modified PCR for tox gene also used for rapid detection
Reservoir / transmission
  • Humans are the only reservoir [1]
  • Transmission via respiratory droplets or direct contact with skin lesions
  • Carriage in pharynx of asymptomatic individuals
  • Rare in HK/developed regions due to universal childhood vaccination; imported cases possible
Key virulence
  • Diphtheria exotoxin (A-B toxin) encoded by tox gene on corynephage β (lysogenic bacteriophage) [1]
  • Fragment A = catalytic: ADP-ribosylates EF-2 (elongation factor 2) → halts host protein synthesis → cell death
  • Fragment B = binding/translocation subunit
  • Only lysogenised (phage-infected) strains produce toxin; non-lysogenised strains are non-toxigenic [1]
  • Toxin causes local tissue necrosis (pseudomembrane) + distant organ damage (myocardium, nerves, kidneys)
Clinical syndromes
  • Pharyngeal/tonsillar diphtheria: grey-white pseudomembrane firmly adherent to pharynx; bleeds on removal; "bull neck" from cervical lymphadenopathy + oedema [1][2]
  • Laryngeal diphtheria → stridor, airway obstruction (paediatric emergency)
  • Myocarditis (toxin-mediated): arrhythmias, heart block, heart failure — major cause of death [1]
  • Neuropathy: bulbar palsy (palatal paralysis → nasal regurgitation), then peripheral demyelinating neuropathy (weeks later) [1]
  • Cutaneous diphtheria: non-healing ulcer with grey membrane (tropical regions)
  • Notifiable disease in Hong Kong [1]
Diagnosis
  • Throat swab (beneath the membrane edge) sent for culture on tellurite agar + Löffler medium [1]
  • Albert/methylene blue stain for metachromatic granules (rapid clue but not confirmatory)
  • Elek test or PCR for tox gene to confirm toxigenicity — critical for public health action [1]
  • Pitfall: do NOT wait for culture results before starting treatment; clinical diagnosis warrants immediate DAT + antibiotics
Treatment
  • Diphtheria antitoxin (DAT) = mainstay; must be given early (neutralises unbound toxin only; cannot reverse toxin already bound to cells) [1]
  • Antibiotics: erythromycin (first-line) or penicillin G — to eradicate organism and stop toxin production [1]
  • Antibiotics alone insufficient without antitoxin
  • Supportive: airway management; cardiac monitoring for myocarditis
  • Close contacts: throat swab + culture; erythromycin prophylaxis × 7–10 days + booster vaccination
Prevention
  • Diphtheria toxoid vaccine (formalin-inactivated toxin) in childhood EPI schedule: DTaP/DTP at 2, 4, 6 months + boosters [1][2]
  • Td (reduced-dose diphtheria + tetanus) booster every 10 years for adults [1]
  • Toxoid = formaldehyde-treated toxin → immunogenic but non-toxic
  • Statutory notifiable disease in Hong Kong; droplet isolation for confirmed/suspected cases [1]
  • Post-exposure: close contacts receive erythromycin prophylaxis + booster toxoid if > 5 years since last dose
Classic traps
  • Pseudomembrane on pharynx: diphtheria vs EBV (infectious mono) vs Group A Strep (no true membrane) vs Vincent's angina (anaerobes, ulcerative) [1]
  • Epiglottitis (H. influenzae type b) causes stridor but no pseudomembrane; "thumb sign" on lateral neck XR
  • ADP-ribosylation of EF-2: C. diphtheriae vs Pseudomonas exotoxin A (same target EF-2) — distinguish from cholera/pertussis toxin which ADP-ribosylate G-proteins [1]
  • Bull neck DDx: Ludwig's angina (floor of mouth) vs diphtheria (pharyngeal membrane + toxin signs)
  • Non-toxigenic C. diphtheriae can still cause pharyngitis/endocarditis but NO systemic toxin effects

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