CORYNEBACTERIAL AND RELATED INFECTIONS is a topic covered in the Harrison's Manual of Medicine.

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Corynebacterium diphtheriae, the causative agent of the nasopharyngeal and skin infection known as diphtheria, is a club-shaped, gram-positive, unencapsulated, nonmotile, nonsporulating rod.

  • The bacteria often form clusters of parallel arrays (palisades) in culture, referred to as Chinese characters.
  • Some strains produce diphtheria toxin, which can cause myocarditis, polyneuropathy, and other systemic toxicities and is associated with the formation of pseudomembranes in the pharynx during respiratory infection.

Epidemiology and Pathogenesis

As a result of routine immunization, fewer than five cases of diphtheria are diagnosed per year in the United States.

  • Low-income countries in Africa and Asia continue to have significant outbreaks; globally, there were ~7000 cases of diphtheria in 2008 and ~5000 deaths related to diphtheria in 2004.
  • C. diphtheriae is transmitted via the aerosol route, primarily during close contact.
  • Diphtheria toxin—the primary virulence factor—irreversibly inhibits protein synthesis, thereby causing the death of the cell.

Clinical Manifestations

  • Respiratory diphtheria: Upper respiratory tract illness due to C. diphtheriae typically has a 2- to 5-day incubation period and is diagnosed on the basis of a constellation of sore throat; low-grade fever; and a tonsillar, pharyngeal, or nasal pseudomembrane.
    • Unlike that of GAS pharyngitis, the pseudomembrane of diphtheria is tightly adherent; dislodging the membrane usually causes bleeding.
    • Massive swelling of the tonsils and “bull-neck” diphtheria resulting from submandibular and paratracheal edema can develop. This illness is further characterized by foul breath, thick speech, and stridorous breathing.
    • Respiratory tract obstruction due to swelling and sloughing of the pseudomembrane can be fatal.
    • Neurologic manifestations may appear during the first 2 weeks of illness, beginning with dysphagia and nasal dysarthria and progressing to cranial nerve involvement (e.g., weakness of the tongue, facial numbness, blurred vision due to ciliary paralysis).
      • Several weeks later, generalized sensorimotor polyneuropathy with prominent autonomic dysfunction (including hypotension) may occur.
      • Pts who survive the acute phase gradually improve.
  • Cutaneous diphtheria: This variable dermatosis is generally characterized by punched-out ulcerative lesions with necrotic sloughing or pseudomembrane formation. Pts typically present to medical care because of nonhealing or enlarging ulcers; the lesions rarely exceed 5 cm in diameter.


A definitive diagnosis is based on compatible clinical findings and detection of C. diphtheriae or toxigenic C. ulcerans (by isolation or histologic identification) in local lesions.

  • The laboratory should be notified that diphtheria is being considered, and appropriate selective media must be used.
  • In the United States, respiratory diphtheria is a notifiable disease; cutaneous diphtheria is not.


Risk factors for death include a long interval between onset of local disease and antitoxin administration; bull-neck diphtheria; myocarditis with ventricular tachycardia; atrial fibrillation; complete heart block; an age of >60 years or <6 months; alcoholism; extensive pseudomembrane elongation; and laryngeal, tracheal, or bronchial involvement.


  • DTaP (diphtheria and tetanus toxoids and acellular pertussis vaccine adsorbed) is recommended for primary immunization of children up to age 7 years; Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis) is recommended as the booster vaccine for children 11–12 years old and as the catch-up vaccine for children 7–10 and 13–18 years old.
  • Td (tetanus and diphtheria toxoids) is recommended for routine booster use in adults at 10-year intervals or for tetanus-prone wounds. When >10 years have elapsed since the last Td dose, adults 19–64 years old should receive a single dose of Tdap.
  • Close contacts of pts with respiratory diphtheria should have throat specimens cultured for C. diphtheriae, should receive a 7- to 10-day course of oral erythromycin or one dose of benzathine penicillin (1.2 mU for persons ≥6 years old; 600,000 U for children <6 years old), and should be vaccinated if immunization status is uncertain.

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