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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

Exam Intelligence

  1. Diphtheria toxin mechanism — ADP-ribosylation of EF-2 — is a classic MCQ favourite. Distinguish from cholera toxin (ADP-ribosylates Gs) and pertussis toxin (ADP-ribosylates Gi). Pseudomonas exotoxin A shares the same EF-2 target but is a different organism [1].

  2. Elek test is the definitive in vitro test for toxin production (immunoprecipitation in agar); PCR for the tox gene is faster but does not confirm actual toxin expression. Exams may test the difference [1].

  3. Toxin is produced ONLY by strains lysogenised by corynephage β — this is a frequently tested virulence concept. Non-lysogenised strains are non-toxigenic [1].

  4. Diphtheria antitoxin (DAT) must be given as early as possible because it neutralises circulating (unbound) toxin only. Once toxin is cell-bound, DAT is ineffective → this is why delayed treatment carries higher mortality [1].

  5. Myocarditis and neuropathy are the two major toxin-mediated complications. Myocarditis occurs in the first 1–2 weeks; neuropathy is delayed (2–8 weeks). Palatal palsy (nasal speech, regurgitation) is the earliest and most characteristic neurological finding [1].

  6. Vaccine is a toxoid (not live, not killed whole organism) — important for MCQs asking about vaccine type classification. Safe in immunocompromised patients [1][2].

  • Pseudomembrane bleeding on removal = classic diphtheria clue; EBV tonsillar exudate wipes off more easily.
  • "Bull neck" in a child with sore throat + grey membrane → think diphtheria before Ludwig's angina (which originates from dental/floor-of-mouth infection, not pharyngeal membrane) [3].
  • Cutaneous diphtheria is often missed in MCQs; it presents as a chronic non-healing ulcer with a grey base, more common in tropical/resource-limited settings.
  • C. diphtheriae vs C. jeikeium (JK): C. jeikeium is a nosocomial multi-drug-resistant skin organism causing line infections in neutropenic patients — do NOT confuse with C. diphtheriae.
  • If asked "which toxin inhibits protein synthesis by the same mechanism as diphtheria toxin?" → answer is Pseudomonas exotoxin A (both ADP-ribosylate EF-2).

  • 2024 Fourth Summative SAQ Q3 [3]: "A 65-year-old gentleman went to the A&E for a 4-day history of sore throat and painful neck swelling. Physical examination showed fever of 39°C, swollen floor of mouth and right painful neck swelling." — (a) Most likely diagnosis; (b) Most common infective origin; (d) Crepitus of the right neck → most likely diagnosis now.
    • Answer: (a) Ludwig's angina; (d) Necrotising fasciitis / descending necrotising mediastinitis. This is a discriminator question — Ludwig's angina (floor of mouth origin, dental source) vs pharyngeal diphtheria (pseudomembrane, toxin complications). The question tests the student's ability to distinguish deep neck space infections from diphtheria when "sore throat + neck swelling" is the stem. Diphtheria would feature a pharyngeal membrane and systemic toxin signs rather than floor-of-mouth swelling and crepitus.

No other past paper question in the indexed set directly tests C. diphtheriae by name. Students should be prepared for MCQ stems featuring: pseudomembrane on the pharynx in an unvaccinated/under-vaccinated child or traveller, toxin mechanism identification, and vaccine type classification.

[1] Lecture slides: GC 105. Medically important microbes what every doctor should know.pdf; GC 219. Infections and tumours in pharynx and oral cavity.pdf; GC 021. Upper respiratory tract infections.pdf
[2] Senior notes: Gen Clerk Anaes + Microbiology Summary.pdf; Adrian Lui Pediatrics Notes.pdf
[3] Past papers: 2024 Fourth Summative SAQ.pdf

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