Mycetoma Medication

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

Medication Summary

When prescribing imidazole antifungals, considering interactions with other medications (eg, rifampin, cyclosporin A, warfarin) that interact with cytochrome P450 is important. Azole administration is contraindicated during pregnancy.

Aminoglycosides can induce ototoxicity and renal damage; therefore, the administration of these drugs must include an evaluation of auditory and kidney function during treatment.

Sulfonamides can produce gastritis, photosensitivity, and a skin eruption that can sometimes be severe (eg, toxic epidermal necrolysis, Stevens-Johnson syndrome). Hematologic adverse effects, including methemoglobinemia, can develop as adverse reactions to these drugs.

The main adverse effect of amphotericin B is renal impairment that can lead to permanent kidney damage. Other adverse reactions include ECG changes, hypokalemia, anemia, thrombocytopenia, and leukopenia.

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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)

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

Trimethoprim-sulfamethoxazole (Bactrim DS, Septra)

Trimethoprim-sulfamethoxazole is a drug of choice; it inhibits bacterial growth by inhibiting the synthesis of dihydrofolic acid. It should be used continuously in combination with another antimicrobial for a 5-week cycle. The cycle may be repeated as necessary.

Amikacin (Amikin)

Amikacin irreversibly binds to the 30S subunit of bacterial ribosomes, blocks the recognition step in protein synthesis, and causes growth inhibition. It should be given continuously for 3 weeks. Although somewhat expensive, it usually is active against the bacteria causing actinomycetoma. Use the patient's ideal body weight for dosage calculation.

Dapsone (Avlosulfon)

Dapsone is bactericidal and bacteriostatic against mycobacteria. Its mechanism of action is similar to sulfonamides, where competitive antagonists of PABA prevent the formation of folic acid, inhibiting bacterial growth. It is the lowest-cost regimen. Change to trimethoprim-sulfamethoxazole if no response occurs after 1 month.

Rifampin (Rimactane, Rifadin)

Rifampin is for use in combination with at least one other agent. It inhibits DNA-dependent bacterial, but not mammalian, RNA polymerase. Cross-resistance may occur.

Imipenem and cilastatin (Primaxin)

This combination is for treatment of multiple-organism infections in which other agents do not have wide-spectrum coverage or are contraindicated owing to the potential for toxicity.

Gentamicin (Garamycin)

Gentamicin is an aminoglycoside antibiotic for coverage of gram-negative bacteria, including Pseudomonas species. It is synergistic with beta-lactamase against enterococci. It interferes with bacterial protein synthesis by binding to the 30S and 50S ribosomal subunits. Dosing regimens are numerous and are adjusted based on creatinine clearance and changes in the volume of distribution, as well as the body space into which the agent needs to distribute. Gentamicin may be given IV/IM. Each regimen must be followed by at least a trough level drawn on the third or fourth dose, 0.5 hour before dosing; one may draw a peak level 0.5 hour after a 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)

Ketoconazole has fungistatic activity. It is an imidazole broad-spectrum antifungal agent; it inhibits the synthesis of ergosterol, causing cellular components to leak, resulting in fungal cell death.

Itraconazole (Sporanox)

Itraconazole has fungistatic activity. It is a 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)

Amphotericin B is a polyene antibiotic produced by a strain of Streptomyces nodosus; it can be fungistatic or fungicidal. It binds to sterols, such as ergosterol, in the fungal cell membrane, causing intracellular components to leak with subsequent fungal cell death.

The 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)

Voriconazole is used for primary treatment of invasive aspergillosis and salvage treatment of Fusarium species or S apiospermum infections. It is a triazole antifungal agent that inhibits fungal cytochrome P-450–mediated 14 alpha-lanosterol demethylation, which is essential in fungal ergosterol biosynthesis.

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