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.
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.
- 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
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Prognosis
The mortality rate for diphtheria is 5-10% but may approach 20% in children <5 years old and adults >40 years of age. 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.
Prevention
- DTaP (diphtheria and tetanus toxoids and acellular pertussis vaccine adsorbed) is recommended for primary immunization of children up to age 6 years; Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis) is recommended for children ≥7 years old and for adults. All adults should receive a single dose of Tdap if they have not received it previously, regardless of the duration since their last dose of Td (tetanus and diphtheria toxoids).
- Td 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 their immunization status is uncertain.
Other Corynebacteria and Related Organisms 
Nondiphtherial Corynebacterium species and related organisms are common components of the normal human flora. Although frequently considered contaminants, these bacteria are associated with invasive disease in immunocompromised hosts.
- C. ulcerans infection is a zoonosis that causes diphtheria-like illness and requires similar treatment.
- C. jeikeium infects pts with cancer or severe immunodeficiency and can cause severe sepsis, endocarditis, device-related infections, pneumonia, and soft-tissue infections. Treatment consists of removal of the source of infection and administration of vancomycin or linezolid.
- C. urealyticum is a cause of sepsis and nosocomial UTI, including alkaline-encrusted cystitis (a chronic inflammatory bladder infection associated with deposition of ammonium magnesium phosphate on the surface and walls of ulcerating lesions in the bladder). Vancomycin and linezolid are effective therapeutic agents.
- Rhodococcus species appear as spherical to long, curved, clubbed gram-positive rods that are often acid fast. The most common presentation-nodular cavitary pneumonia of the upper lobe (similar to tuberculosis and nocardiosis) in an immunocompromised host-often occurs in conjunction with HIV infection. Vancomycin is the drug of choice, but macrolides, clindamycin, rifampin, and TMP-SMX have also been used to treat these infections.
- Arcanobacterium haemolyticum can cause pharyngitis and chronic skin ulcers, often in association with a scarlatiniform rash similar to that caused by GAS. The organism is susceptible to β-lactam agents, macrolides, fluoroquinolones, clindamycin, vancomycin, and doxycycline. Penicillin resistance has been reported.