Mycetoma Medication

Updated: Jan 09, 2017
  • Author: Folusakin O Ayoade, MD; Chief Editor: Pranatharthi Haran Chandrasekar, MBBS, MD  more...
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Medication

Medication Summary

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

Actinomycetoma is a bacterial infection that can respond to antibiotics [24] if treatment is administered early in the course of the disease. [25] A combination of 2 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 (TMP-SMZ), dapsone (diaminodiphenylsulfone), and streptomycin sulfate. Amikacin can be substituted for streptomycin but is usually kept as a second-line drug because of its cost.

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. [26] However, a case of actinomycetoma was reported as still improving after 5 years of continued treatment with cotrimoxazole only. [27]

In one case report, a patient required salvage therapy with amikacin and imipenem for 6 months. [28] 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. [29, 30]

Although eumycetoma may respond partially to antifungal agents, surgical removal is usually done first. [31] 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 side effects and multiple drug interactions. [32] ​ Fluconazole is also discouraged because of intrinsic resistance. [33]

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 Madurella mycetomatis, but terbinafine is only moderately active. Since posaconazole has an excellent safety profile, it might provide an important alternative in mycetoma therapy. [34]

Madurella mycetomatis is not susceptible to the echinocandins. [35]

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Antibiotics

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of a clinical setting suggestive of actinomycetoma.

Doxycycline (Bio-Tab, Doryx, Doxy, Periostat, Vibramycin, Vibra-Tabs)

Drug of choice. Broad-spectrum, synthetically derived bacteriostatic antibiotic in the tetracycline class. Almost completely absorbed, concentrates in bile, and is excreted in urine and feces as a biologically active metabolite in high concentrations. Inhibits protein synthesis and, thus, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. May block dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

Trimethoprim-sulfamethoxazole (Bactrim DS, Septra)

DOC; inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. Should be used continuously in combination with another antimicrobial for 5 wk. Cycle may be repeated prn.

Amikacin (Amikin)

Irreversibly binds to 30S subunit of bacterial ribosomes, blocks recognition step in protein synthesis, and causes growth inhibition.

Should be given continuously for 3 wk. Although somewhat expensive, it usually is active against the bacteria causing actinomycetoma. Use the patient's IBW for dosage calculation.

Dapsone (Avlosulfon)

Bactericidal and bacteriostatic against mycobacteria. Mechanism of action is similar to sulfonamides where competitive antagonists of PABA prevent formation of folic acid, inhibiting bacterial growth. Lowest-cost regimen. Change to TMP-SMZ if no response occurs after 1 mo.

Rifampin (Rimactane, Rifadin)

For use in combination with at least 1 other agent. Inhibits DNA-dependent bacterial but not mammalian RNA polymerase. Cross-resistance may occur.

Imipenem and cilastatin (Primaxin)

For treatment of multiple-organism infections in which other agents do not have wide spectrum coverage or are contraindicated due to potential for toxicity.

Gentamicin (Garamycin)

Aminoglycoside antibiotic for gram-negative coverage bacteria, including Pseudomonas species. Synergistic with beta-lactamase against enterococci. Interferes with bacterial protein synthesis by binding to 30S and 50S ribosomal subunits. Dosing regimens are numerous and are adjusted based on CrCl and changes in volume of distribution, as well as body space into which agent needs to distribute. Gentamicin may be given IV/IM. Each regimen must be followed by at least trough level drawn on third or fourth dose, 0.5 h before dosing; may draw peak level 0.5 h after 30-min infusion.

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Antifungal agents

Class Summary

In combination with surgical therapy, antifungal agents may help to attain partial response in cases of eumycetoma.

Ketoconazole (Nizoral)

Fungistatic activity. Imidazole broad-spectrum antifungal agent; inhibits synthesis of ergosterol, causing cellular components to leak, resulting in fungal cell death.

Itraconazole (Sporanox)

Fungistatic activity. Synthetic triazole antifungal agent that slows fungal cell growth by inhibiting cytochrome P-450–dependent synthesis of ergosterol, a vital component of fungal cell membranes.

Amphotericin B (Fungizone)

Polyene antibiotic produced by a strain of Streptomyces nodosus; can be fungistatic or fungicidal. Binds to sterols, such as ergosterol, in the fungal cell membrane, causing intracellular components to leak with subsequent fungal cell death.

Conventional formulation (complexed with deoxycholate) has a poor tolerability profile. Liposomal amphotericin B incorporates the drug into small unilamellar liposomes; this formulation retains the antifungal activity with less hypokalemia, anemia and infusion reactions, and far less nephrotoxicity than the conventional formulation.

Although the acquisition cost of liposomal amphotericin B is considerably higher than that of the conventional formulation, when adverse effects are considered, the calculated total costs of treatment for fungal infections are not clearly different.

Voriconazole (VFEND)

Used for primary treatment of invasive aspergillosis and salvage treatment of Fusarium species or S apiospermum infections. A triazole antifungal agent that inhibits fungal cytochrome P450-mediated 14 alpha-lanosterol demethylation, which is essential in fungal ergosterol biosynthesis.

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