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, including those of C. ulcerans and C. pseudotuberculosis, 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, ∼7000 cases of diphtheria were reported in 2014, but many more cases likely go unreported.
  • C. diphtheriae is transmitted by aerosols, 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.

Treatment: Diphtheria

  • Diphtheria antitoxin is the most important component of treatment and should be given as soon as possible. To obtain antitoxin, contact the Emergency Operations Center at the Centers for Disease Control and Prevention (CDC) (770-488-7100) after first contacting the state health department. See for further information.
  • Antibiotic therapy is administered for 14 days to prevent transmission to contacts. The recommended options are (1) procaine penicillin G (600,000 U IM q12h in adults; 12,500–25,000 U/kg IM q12h in children) until the pt can take oral penicillin V (125–250 mg qid); or (2) erythromycin (500 mg IV q6h in adults; 40–50 mg/kg per day IV in 2–4 divided doses in children) until the pt can take oral erythromycin (500 mg qid).
    • Rifampin and clindamycin are other options for pts who cannot tolerate penicillin or erythromycin.
    • Cultures should document eradication of the organism 1 and 14 days after completion of antibiotic therapy. If the organism is not eradicated after 2 weeks of therapy, an additional 10-day course followed by repeat cultures is recommended.
  • Respiratory isolation and close monitoring of cardiac and respiratory functions should be instituted.

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