Mycetoma Treatment & Management

Updated: Apr 07, 2021
  • Author: Lucio Vera-Cabrera, PhD; Chief Editor: Pranatharthi Haran Chandrasekar, MBBS, MD  more...
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Treatment

Approach Considerations

Treatment for mycetoma is generally a combination of medical and surgical therapy. Medical therapy is often prolonged, lasting for months to years. While medical therapy alone may be sufficient for actinomycetoma, surgery is generally needed for eumycetoma.

In the treatment of mycetoma, antibiotic or antifungal therapy should be attempted first and may need to be combined with surgery, [6] especially for eumycetoma lesions in the extremities. [51]

External beam radiotherapy in doses ranging from 3.5-14 Gy has been considered successful treatment in a few selected cases. [52]

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Medical Care

Eumycetoma

Although eumycetoma may respond partially to antifungal agents, surgical removal is usually done first. [53] The most successful treatment option for eumycetomas is itraconazole 200 mg twice daily. This triazole antifungal is considered the criterion standard for eumycetomas. The less-expensive ketoconazole is no longer favored owing to adverse effects and multiple drug interactions. [54] Fluconazole is also discouraged because of intrinsic resistance. [55]

P boydii (S apiospermum) mycetoma should be treated primarily with voriconazole, although it may also respond to itraconazole. Other agents that cause eumycetoma may respond intermittently to itraconazole or amphotericin B.

Voriconazole is the drug of choice for invasive infections caused by agents of eumycetoma in immunocompromised patients.

Posaconazole is highly active in vitro against M mycetomatis, but terbinafine is only moderately active. Since posaconazole has an excellent safety profile, it might provide an important alternative in mycetoma therapy. [56]

M mycetomatis is not susceptible to the echinocandins. [57]

Treatment for eumycetoma is generally less successful than for actinomycetoma. In adults weighing 70 kg, ketoconazole 400 mg daily, itraconazole 300 mg daily, and intravenous amphotericin B 50 mg daily, have been used with some success in cases of eumycetoma. Isolated cases of successful treatment with voriconazole and posaconazole have been reported. [58, 59] Therapy is suggested for 1-2 years (or greater) for complete eradication, unless adverse effects warrant cessation of medication.

In two cases, the combination of itraconazole and terbinafine has been used, resulting in remission of the disease. [60] Combined medical and surgical treatment is a viable therapy for mycetoma caused by fungi.

Actinomycetoma

Actinomycetoma is a bacterial infection that can respond to antibiotics [61] if treatment is administered early in the course of the disease. [62] A combination of two drugs in 5-week cycles is used. If needed, the cycles can be repeated once or twice. The following agents have been used in combination: trimethoprim-sulfamethoxazole, dapsone (diaminodiphenylsulfone), and streptomycin sulfate. Amikacin can be substituted for streptomycin but is usually kept as a second-line drug because of its cost.

Current treatment of actinomycetoma is trimethoprim-sulfamethoxazole 7.5-40 mg/kg daily divided in two oral doses for several months or years. In certain anatomical sites (eg, thorax, head), extensive lesions, or cases recalcitrant to the above therapy, amikacin 15 mg/kg intramuscularly or intravenously daily should be added. [63] Every 3 weeks, periodic audiometric and creatine clearance analysis must be performed. This treatment is maintained for 5-20 weeks and, in rare cases, for a longer period, depending on the clinical response and renal and auditory adverse effects.

The combination of amikacin with cotrimoxazole (so-called Welsh regimen) is increasingly favored by many. Adding rifampin to the Welsh regimen (modified Welsh regimen) allows for remissions without recurrence. [64] However, a case of actinomycetoma was reported as still improving after 5 years of continued treatment with cotrimoxazole only. [65]

In one case report, a patient required salvage therapy with amikacin and imipenem for 6 months. [66] An effective and convenient regimen combining a short course of intravenous gentamicin with a 6-month oral course of cotrimoxazole and doxycycline has been described. [67, 68]

Other antimicrobials such as minocycline, amoxicillin-clavulanic acid, streptomycin, imipenem, meropenem, and rifampin have been used with variable success. [61, 69] An oxazolidinone, linezolid, has been proven to be active in vitro, in vivo, and in clinical nocardial infections. Other experimental oxazolidinone drugs such as DA-7867 and DA-7218 (tedizolid) are active in vitro and in experimental models of N brasiliensis infection, and its successful use in human nocardiosis opens the possibility to treat actinomycetoma cases caused by Nocardia species. [9, 70]

Fluoroquinolones such as gatifloxacin and moxifloxacin have been observed to be active in vitro and in a murine model of actinomycetoma by N brasiliensis. However, clinical assays are necessary to determine their usefulness in human cases. [71, 72]

Regarding treatment, refer to the article "Actinomycetoma and advances in its treatment" by Welsh et al, which outlines current treatment for unresponsive or disseminated infection. [61, 73, 74]

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Surgical Care

Surgery is recommended for localized mycetoma lesions that can be excised completely without residual disability. Surgical reduction of large lesions can improve the patient's response to medical treatment. [75] However, partial surgical resection without subsequent use of appropriate antimicrobial or antifungal agents is prone to failure.

In eumycetoma, surgical therapy is an option if the patient's disease has not responded to antifungal medical treatment, in local lesions, and in patients with massive disease. In these cases, wide local and debulking excisions and even amputation are used together with medical fungal treatment. [76, 77]

In actinomycetoma surgical treatment, including amputation, is infrequently indicated.

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Consultations

Consultation with specialists in infectious disease or tropical medicine is advised in areas of the world where mycetoma is unfamiliar.

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Prevention

There is currently no vaccine.

Educate patients to avoid activities that expose them to agents of mycetoma. Instruct patients to avoid carrying sticks and thorny branches that have had contact with soil, especially if contaminated with cattle dung. [17] Footwear and protective clothing in at-risk populations, especially in developing countries, is also recommended.

The glycolytic enzyme fructose-bisphosphate aldolase (FBA) is expressed on the hyphae present in the mycetoma grain. FBA antibody levels were found to be significantly higher in eumycetoma patient sera when compared with healthy Sudanese controls. Therefore, FBA might be useful as candidate antigen for a future vaccine against mycetoma. [78]

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Long-Term Monitoring

Patients with mycetoma should receive maintained medical treatment and follow-up care for several months to years.

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