Agents of Mycetoma

OVERVIEW: What every clinician needs to know

Pathogen name and classification

Mycetoma may be caused by filamentous bacteria (actinomycotic mycetoma or actinomycetoma) or fungi (eumycotic mycetoma or eumycetoma). The most common bacterial causes are Nocardia brasiliensis, Actinomadurae madurae, Streptomyces somaliensis, and Actinomadura pelletieria. The most common fungal causes are Madurella mycetomatis, Madurella grisea, and Scedosporium apiopsermum/Pseudallescheria boydii.

What is the best treatment?

  • Mycetoma is a difficult disease to successfully treat. Treatment typically includes both antimicrobial therapy and surgery. Surgery alone is rarely successful. No treatment of choice has been established. Establishing whether the mycetoma is bacterial or fungal is critical to selecting a medical regimen. Knowledge of the specific agent can further direct therapy.

  • Bacterial (actinomycotic) mycetoma is most commonly treated with trimethoprim/sulfamethoxazole (TMP/SMX) or dapsone, often combined initially for weeks to months with a parenteral aminoglycoside. Reports of success with streptomycin, amikacin, and gentamicin containing regimens have been reported. The addition of doxycycline to a gentamicin/TMP/SMX regimen has also been described.

  • Alternate therapies, which have been more recently described, include use of imipenem or amoxicillin/clavulanate.

  • Fungal (eumycotic) mycetoma is most commonly treated with itraconazole (100-200 mg twice daily) or ketoconazole (200-400 mg daily). Treatment is typically given for months to years.

  • Alternate therapies include terbinafine (500 mg twice daily) or posaconazole (400 mg twice daily) or voriconazole (200 mg twice daily). Voriconazole, with its excellent in vitro activity against S. apiospermum/P. boydii, should be the drug of choice for mycetoma against this otherwise resistant organism.

How do patients contract this infection, and how do I prevent spread to other patients?

  • Epidemiology

    Cases have been described throughout the world. Highest prevalence is seen in tropical and subtropical climates. Endemic regions include the Indian subcontinent, the Middle East, Africa, and Central and South America. Sudan has a very high prevalence.

    The causative agents of mycetoma are found in the environment and cause infection after inoculated by splinters or other minor or unobserved trauma.

    Mycetoma more commonly affects men 20-40 years of age who work outdoors (e.g., farmers). It is postulated that in developing nations with warm climates this is due to lack of protective clothing or footwear.

  • Infection control issues

    Mycetoma is not spread between humans or from animals to humans.

    No vaccination is currently available.

What host factors protect against this infection?

  • The response in mycetoma appears to be chiefly one of innate immunity, involving complement-dependent chemotaxis and polymorphonuclear cells. No predisposing immune defects have been identified.

  • Acquired or therapy induced immune suppression has not been described as a risk factor for either bacterial or fungal mycetoma.

  • Three phases of the host response to mycetoma have been described. These include neutrophil adherence and degranulation, leading to grain disintegration; replacement of neutrophils with macrophages to clear grain and neutrophil debris; and formation of epithelioid granuloma.

What are the clinical manifestations of infection with this organism?

  • Mycetoma is a chronic, progressive disease of the skin and subcutaneous tissue, typically of the foot or lower extremity. Disease presents with the classic triad of localized tissue swelling, development of sinus tracts, and production/discharge of grains. Grains (or granules) are composed of aggregations of the infecting organism formed within the sinus tracts. Disease typically begins as a single, painless nodule at the site of inoculation. This nodule slowly grows, and, ultimately, sinus tracts form and discharge grains that can be black, white, or red, depending on the organism.

What common complications are associated with infection with this pathogen?

  • Complications include disfigurement, secondary bacterial infection, and spread to bone (i.e., osteomyelitis).

How should I identify the organism?

The causative agents of mycetoma are found in the environment and cause infection after inoculated by splinters or other minor or unobserved trauma.

  • Diagnosis is made clinically from observation of the triad of a swollen nodular skin/subcutaneous lesion, sinus tracts, and grain production. Microscopic examination of extruded grains can often differentiate bacterial from fungal disease.

  • Culture of grains can identify the etiologic agent involved. Care must be taken to avoid contamination of culture with skin surface bacteria. If extruded grains are used, some experts suggest rinsing these with 70% alcohol or an antibiotic-containing solution prior to culture.

  • Serological testing is available in some endemic areas and has been used to monitor response to therapy.

How does this organism cause disease?

  • The pathophysiology of this disease is not well understood.

  • Some fungi that produce mycetoma also produce melanin, which is a virulence factor for many fungi. Toxins are not produced by the organisms causing mycetoma.

WHAT’S THE EVIDENCE for specific management and treatment recommendations?

No controlled trials have been performed, and treatment is based primarily on clinical experience.

Bustamante, B, Campos, PE, Kauffman, CA, Pappas, PG, Sobel, JD, Dismukes, WE. “Eumycetoma”. Essentials of clinical mycology. 2011. pp. 415-25.

Fahal, AH, el Toum, EA, Hassan, AM. “The host tissue reaction to Madurella mycetomatis: new classification”. J Med Vet Mycol. vol. 33. 1995. pp. 15-7.

Queiroz-Telles, F, McGinnis, MR, Salkin, I. “Subcutaneous mycoses”. Infect Dis Clin N Am. vol. 17. 2001. pp. 59-85.

Welsh, O. “Mycetoma: current concepts in treatment”. Int J Dermatol. vol. 30. 1991. pp. 387-98.