Corynebacterium

Corynebacteria are gram-positive, club-shaped bacilli. Corynebacteria are commonly isolated on tellurite or Loeffler’s media and have characteristic metachromatic granules. The major pathogenic species is Corynebacterium diphtheriae, which causes diphtheria—a severe upper respiratory infection. The characteristic findings of diphtheria include pharyngeal pseudomembranes (grayish tonsillar exudates), severe pharyngitis, and “bull’s neck” lymphadenopathy. Treatment is primarily through passive immunization with antitoxin and antibiotics. Prevention is via the diphtheria toxoid vaccine.

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General Characteristics

Basic features

General characteristics of Corynebacterium species include:

  • Gram-positive, club-shaped bacilli (coryne = club shaped)
  • Non-motile
  • Non-spore forming
  • Non-encapsulated
  • Aerobic or facultatively anaerobic
  • Contain metachromatic (volutin) granules 

Micrograph of Corynebacterium diphtheriae

Image: “12163” by the CDC/Graham Heid. License: Public domain.

Growth and biochemical properties

  • Catalase positive (split hydrogen peroxide into water and oxygen)
  • Oxidase negative, indole negative
  • Ferment glucose, starch, and glycogen
  • Grow well at 37°C (98.6°F) on blood or serum-containing media:
    • Hoyle’s/Tinsdale’s agar (tellurite medium; C. diphtheriae forms black colonies)
    • Loeffler’s medium (enhances development of metachromatic granules)

Clinically relevant species

  • C. diphtheriae: 
    • Major pathogenic species
    • Causes diphtheria (pharyngitis and cutaneous forms)
  • Non-diphtherial Corynebacterium (diphtheroids):
    • Mostly contaminants
    • May be pathogenic, especially in immunocompromised hosts
    • C. minutissimum:
      • Normal skin inhabitant
      • Can cause erythrasma: superficial infection of intertriginous areas
    • Many species cause diseases in domestic animals.

Corynebacterium diphtheriae

Epidemiology

  • In immunized individuals, the rate is low: < 5 per 100,000.
  • Remains endemic in certain parts of the world (Brazil, Nigeria, India, certain parts of the former Soviet Union)
  • No racial or sex predilection
  • Can affect children and adults

Transmission

  • Humans are the only known reservoir.
  • Airborne droplets
  • Direct contact with respiratory secretions
  • Contact with skin lesions
  • Can be transmitted by immunized and asymptomatic carriers

Virulence factors

  • Not an invasive organism
  • Pathogenicity is based on diphtheria toxin (exotoxin):
    • Only produced if lysogenized by a β-bacteriophage
    • Has 2 subunits:
      • A—active
      • B—binding
    • B binds to the cell membrane and A enters the cell.
    • Ribosylation of elongation factor (EF-2)
    • Inhibits protein synthesis
    • Causes cell death

Clinical presentation

Diphtheria (respiratory):

  • Sore throat, malaise, cervical lymphadenopathy, low-grade fever
  • Pharyngeal erythema with spots of white and gray exudate
  • Can also have nasal, laryngeal, and tracheobronchial forms
  • Pseudomembranes:
    • Form in ⅓ of cases
    • Composed of fibrin, necrotic debris, inflammatory cells, and organisms
    • Tightly adherent to underlying tissue; bleeds with scraping
    • Can spread to any portion of the respiratory tract
  • “Malignant diphtheria”:
    • Associated with extensive pseudomembranes (“pseudomembranous pharyngitis”)
    • Severe “bull’s neck” lymphadenopathy
    • Severe swelling of tonsils and uvula
    • Can result in airway obstruction, respiratory stridor, and eventual death
  • Exam tip: A common question stem may include an immigrant with a sore throat; physical exam reveals tonsils with grayish exudate.

Complications/systemic toxemia:

  • Cardiac:
    • Myocarditis
    • Arrhythmias
  • Neurologic:
    • Local neuropathies
    • Cranial neuropathies
    • Peripheral neuritis
  • Renal: renal failure from hypertension or direct exotoxin effects

Cutaneous (wound) diphtheria:

  • Initial papule that becomes a chronic, non-healing ulcer
  • Ulcer is usually covered with a grey membrane.
  • May be caused by toxin or non-toxin-producing strains
  • In the United States, most common among alcoholic homeless men or drug users

Identification

  • Cultures:
    • Should be obtained from throat or nose, including a portion of membrane
    • Cultured on Loeffler’s or tellurite media
  • Toxin detection:
    • Elek’s test: isolates toxin-producing bacteria from the pseudomembrane
    • Enzyme immunoassay (EIA)

Prevention

  • Toxoid vaccine
  • Infants are protected by maternal antibodies.

Management

  • Passive immunization or anti-toxin: 1st line
  • Antibiotics: Erythromycin or penicillin are the 1st choices for 14 days.
  • Supportive management: 
    • Airway protection
    • Bedrest

Mnemonic

ABCDEFGs of Corynebacterium diphtheriae”:

  • ADP-ribosylation
  • β-bacteriophage
  • Corynebacterium
  • Diphtheriae
  • Elongation Factor 2 (EF-2)
  • Granules

References

  1. Barroso L.F., & Pegram P.S. (2020). Clinical manifestations, diagnosis, and treatment of diphtheria. UpToDate. Retrieved December 28, 2020, from https://www.uptodate.com/contents/clinical-manifestations-diagnosis-and-treatment-of-diphtheria?search=diphtheria&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1#H11
  2. Barroso L.F., & Pegram P.S. (2019). Epidemiology and pathophysiology of diphtheria. UpToDate. Retrieved December 28, 2020, from https://www.uptodate.com/contents/epidemiology-and-pathophysiology-of-diphtheria?search=diphtheria&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2
  3. Frassetto, L.A. (2019). Corynebacterium Infections Treatment & Management. https://emedicine.medscape.com/article/215100-treatment
  4. Nisha R. (2020). Corynebacterium diphtheriae: Properties, Pathogenesis, and Lab Diagnosis. https://microbeonline.com/corynebacterium-diphtheriae-properties-pathogenesis-diagnosis/

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