Reports on medical treatment in eumycetoma are scarce and inadequate. Over the years and till now, the treatment of eumycetoma was based on personal clinical experience and on the results of sporadic case reports, rather than controlled clinical trials. In general, massive surgical excisions or amputation of affected part is the treatment of choice.
Various antifungal agents have been tried with little success. This is perhaps surprising, as the eumycetoma causative agents are low-grade infective organisms and their eradication should be readily achieved by the administration of safe systemically antifungal drugs.
Amphotericin B has been used with limited success and it is no longer popular due to its serious toxic side effects. The combination of griseofulvin 1.5 g/day given orally and 60,0000–80,0000 IU of procaine penicillin was a popular regime for a while, but it had low cure and high recurrence rates (Unpublished data).
The most popular treatment regimens nowadays for eumycetoma are ketoconazole 400–800 mg/day or itraconazole 400 mg/day for extended periods of time. The treatment duration ranges from few months to several years with a mean duration of 12 months.
These drugs have many serious side effects. The side effects are more noticeable with ketoconazole, and these include hepatotoxicity, gynecomastia, lip dryness and ulceration, skin darkness and decreased libido. Recently,the FDA and EMA banned this drug due to its toxicity. Both drugs are probably excreted in the milk, and therefore mothers who are under treatment should not breast feed. There are no adequate and well-controlled studies on the effects of these drugs in pregnancy. Therefore, they should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus.
Both of these drugs alone are not curative in most eumycetoma patients, but they help in localizing the disease. In most patients, after completion of treatment with ketoconazole or itraconazole, the lesions were found to be well localized, encapsulated within thick capsules and were easily excised surgically.
However, grain colonies in these lesions were consistently encountered and they were viable on culture. In these patients, the postoperative surgical biopsies showed no significant changes in the morphology of the grains, and the presence of between five and seven grains in every cavity, which was well walled by fibrous tissue was a common finding. The reaction surrounding the grains was commonly type I and II tissue reactions. Type III tissue reactions, indicating healing, were rarely encountered.
In vitro susceptibilities of Madurella mycetomatis, the most common eumycetoma causative organism, to amphotericin B, fluconazole, itraconazole, ketoconazole, 5-flucytosine, and voriconazole were determined. The organism appeared to be most susceptible to the azoles group; ketoconazole, itraconazole and voriconazole, with minimum inhibitory concentrations (MICs) of 0.125, 0.064 and 0.125 µg/ml,
respectively. These MICs correlate with attainable serum levels.
Fluconazole was the least effective azole, inhibiting the fungal growth at MIC 90 of 16.90 µg/ml. Although these MICs are high, they still meet physiologically attainable serum levels. Amphotericin B appeared to be less effective than ketoconazole, itraconazole and voriconazole (MIC 2 µg/ml).
Interestingly, M. mycetomatis also proved to be susceptible to tea-tree oil, with a MIC 90 of 0.25% (v/v). However, it appeared to be resistant to 5-flucytosine and artemisinin. These susceptibility tests indicate that M. mycetomatis is extremely susceptible to the azoles group; ketoconazole and itraconazole, which are currently used in the medical treatment of eumycetoma caused by this organism.
Surprisingly, although some case reports and personal experiences showed that ketoconazole and itraconazole treatment resulted in complete cure in some patients, but the clinical response to both agents in most patients is often poor.
The black compound in the M. mycetomatis grain is melanin produced by the organism. It was thought to protect the fungus from the host immune system and antifungal agents; a fact that was proved experimentally. This may explain the poor response to ketoconazole and itraconazole in clinical practice.
There are some sporadic case reports on the susceptibility of eumycetoma causative organisms to various antifungals including terbinafine, posaconazole, voriconazole, caspofungin and anidulafungin, but these need further clinical trials to establish their therapeutic potential, safety and efficacy for the treatment of eumycetoma.
Local administration of mycetoma chemotherapeutic agents was used, but the results were not impressive with a high rate of failure and complications.