eMedicine Specialties > Infectious Diseases > Skin and Soft-Tissue Infections
Mycetoma: Treatment & Medication
Updated: Aug 30, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
In the treatment of mycetoma, antibiotic or antifungal therapy should be attempted first and may need to be combined with limited surgery, especially for small eumycetoma lesions in the extremities.3
External beam radiotherapy in doses ranging from 3.5-14 Gy has been considered successful treatment in a few selected cases.4
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; however, partial surgical resection without subsequent use of appropriate antimicrobial or antifungal agents is prone to failure.
Consultations
Consultation with specialists in infectious disease or tropical medicine is advised in areas of the world where mycetoma is unfamiliar.
Medication
Actinomycetoma is a bacterial infection that can respond to antibiotics if treatment is administered early in the course of the disease. 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. Rifampin has been used as a second-line drug in resistant cases. In one case report, a patient required salvage therapy with amikacin and imipenem for 6 months.5 An effective and convenient regimen combining a short course of intravenous gentamicin with a 6-month oral course of cotrimoxazole and doxycycline has recently been described.6
Eumycetoma may respond partially to antifungal agents, although surgical therapy is preferred for localized disease. Madurella mycetomatis mycetoma may respond to ketoconazole (200 mg bid). 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 (200 mg bid) or amphotericin B. The minimum treatment duration is 10 months. Voriconazole is the drug of choice for invasive infections caused by agents of eumycetoma in immunocompromised patients.
Antibiotics
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.
Adult
200 mg/d PO/IV divided bid
Pediatric
Not established
Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can increase hypoprothrombinemic effects of anticoagulants; tetracyclines can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy
Documented hypersensitivity; severe hepatic dysfunction
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last one-half of pregnancy through age 8) can cause permanent discoloration of teeth; Fanconi-like syndrome may occur with outdated tetracyclines
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.
Adult
160 mg TMP/800 mg SMZ PO q6h
Pediatric
<2 months: Not recommended
>2 months: 8 mg/kg TMP 40 mg/kg SMZ PO bid
May increase PT when used with warfarin (perform coagulation tests, and adjust dose accordingly); coadministration with dapsone may increase blood levels of both drugs; coadministration of diuretics increases incidence of thrombocytopenia purpura in elderly patients; phenytoin levels may increase with coadministration; may potentiate effects of methotrexate in bone marrow depression; hypoglycemic response to sulfonylureas may increase with coadministration; may increase levels of zidovudine
Documented hypersensitivity; megaloblastic anemia due to folate deficiency; do not use during pregnancy (at term) or breastfeeding
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Discontinue at first appearance of skin rash or sign of adverse reaction; obtain CBCs frequently; discontinue therapy if significant hematologic changes occur; higher risk of hematologic toxicity in renal allograft recipients; goiter, diuresis, and hypoglycemia may occur; prolonged IV infusions or high doses may cause bone marrow depression (if signs occur, give 5-15 mg/d leucovorin); caution in folate deficiency (eg, patients with chronic alcoholism, elderly patients, patients receiving anticonvulsant therapy, patients with malabsorption syndrome); hemolysis may occur in patients deficient of G-6-PD; patients with AIDS may not tolerate or respond to TMP-SMZ; caution in renal or hepatic impairment (perform urinalyses and renal function tests during therapy); give fluids to prevent crystalluria and stone formation
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.
Adult
15 mg/kg/d IV/IM qd or divided bid; not to exceed 1.5 g/d regardless of higher BW
Pediatric
Administer as in adults
Coadministration with other aminoglycosides, penicillins, cephalosporins, and amphotericin B increases nephrotoxicity; enhances effects of neuromuscular blocking agents; causes respiratory depression; irreversible hearing loss may occur with coadministration of loop diuretics
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Not intended for long-term therapy; caution in patients with renal failure (not on dialysis), hypocalcemia, myasthenia gravis, and conditions that depress neuromuscular transmission; risk of nephrotoxicity and ototoxicity
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.
Adult
100 mg PO bid
Pediatric
Not established
May inhibit anti-inflammatory effects of clofazimine; hematologic reactions may increase with folic acid antagonists, eg, pyrimethamine (monitor for agranulocytosis during the second and third mo of therapy); probenecid increases toxicity; TMP may increase toxicity of both drugs; due to increase in renal clearance, levels may decrease significantly when administered concurrently with rifampin
Documented hypersensitivity; G-6-PD deficiency
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Perform weekly blood counts for the first mo; then, perform WBC counts monthly for 6 mo and semiannually thereafter; discontinue if significant reduction in platelets, leukocytes, or hematopoiesis is observed; caution in methemoglobin reductase deficiency, G-6-PD deficiency (patients receiving >200 mg/d), or hemoglobin M due to high risk for hemolysis and Heinz body formation; caution in patients exposed to other agents or conditions (eg, infection, diabetic ketosis) capable of producing hemolysis; peripheral neuropathy can occur (rare); phototoxicity may occur when exposed to UV light
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.
Adult
10 mg/kg/d PO qd
Pediatric
10 mg/kg/d PO qd; not to exceed 600 mg/d
Induces microsomal enzymes, which may decrease effects of acetaminophen, oral anticoagulants, barbiturates, benzodiazepines, beta-blockers, chloramphenicol, oral contraceptives, corticosteroids, dapsone, mexiletine, cyclosporine, digitoxin, disopyramide, estrogens, hydantoins, methadone, clofibrate, quinidine, dapsone, tazobactam, sulfonylureas, theophyllines, tocainide, and digoxin; blood pressure may increase with coadministration of enalapril; coadministration with isoniazid may result in higher rate of hepatotoxicity than with either agent alone (discontinue 1 or both agents if alterations in LFTs occur)
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May cause abnormal liver function, drug fever, flu syndrome, or hematological cytopenias; obtain CBCs and baseline clinical chemistries prior to and throughout therapy; in liver disease, weigh benefits against risk of further liver damage; interruption of therapy and high-dose intermittent therapy are associated with thrombocytopenia that is reversible if therapy is discontinued as soon as purpura occurs; if treatment is continued or resumed after appearance of purpura, cerebral hemorrhage or death 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.
Adult
Base initial dose on severity of infection and administer in equally divided doses; 0.5-1 g IV q6h; not to exceed 3-4 g/d
Alternate dose: 500-750 mg IM q12h
Pediatric
<12 years: Not established; 15-25 mg/kg/dose IV q6h suggested for > 3 mo
Fully susceptible organisms: Not to exceed 2 g/d
Infections with moderately susceptible organisms: Not to exceed 4 g/d
>12 years: Administer as in adults
Coadministration with cyclosporine may increase adverse CNS effects of both agents; coadministration with ganciclovir may result in generalized seizures
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Adjust dose in renal insufficiency; avoid use in children <12 y
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.
Adult
80 mg IV bid
Pediatric
Not established
Coadministration with other aminoglycosides, cephalosporins, penicillins, and amphotericin B may increase nephrotoxicity; because aminoglycosides enhance effects of neuromuscular blocking, agents prolonged respiratory depression may occur; coadministration with loop diuretics may increase auditory toxicity of aminoglycosides; possible irreversible hearing loss of varying degrees may occur (monitor regularly)
Documented hypersensitivity; non-dialysis dependent renal insufficiency
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Narrow therapeutic index (not intended for long-term therapy); caution in renal failure (not on dialysis), myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission; adjust dose in renal impairment
Antifungal agents
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.
Adult
200 mg PO bid
Pediatric
<2 years: Not established
>2 years: 3.3-6.6 mg/kg/d PO single dose
Isoniazid may decrease bioavailability; coadministration decreases effects of either rifampin or ketoconazole; may increase effect of anticoagulants; may increase toxicity of corticosteroids and cyclosporine (cyclosporine dosage can be adjusted); may decrease theophylline levels
Documented hypersensitivity; fungal meningitis
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Hepatotoxicity may occur; may reversibly decrease corticosteroid serum levels (adverse effects avoided with dose of 200-400 mg/d); administer antacids, anticholinergics, or H2 blockers at least 2 h after taking ketoconazole
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.
Adult
200 mg/d PO; not to exceed 400 mg/d; increase in 100-mg increments if no improvement (administer >200 mg/d in divided doses)
200 mg IV bid for 4 doses, followed by 200 mg/d
Pediatric
Not established; suggested dose of 100 mg/d
Antacids may reduce absorption of itraconazole; edema may occur with coadministration of calcium channel blockers (eg, amlodipine, nifedipine); hypoglycemia may occur with sulfonylureas; may increase tacrolimus and cyclosporine plasma concentrations when high doses are used; rhabdomyolysis may occur with coadministration of HMG-CoA reductase inhibitors (ie, lovastatin, simvastatin); coadministration with cisapride can cause cardiac rhythm abnormalities and death; may increase digoxin levels; coadministration may increase plasma levels of midazolam or triazolam; phenytoin and rifampin may reduce levels (phenytoin metabolism may be altered)
Documented hypersensitivity; coadministration with cisapride may cause adverse cardiovascular effects (possibly death)
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in hepatic insufficiencies
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.
Adult
3-5 mg/kg/d IV of liposomal amphotericin B over approximately 120 min
Pediatric
Administer as in adults
Antineoplastic agents may enhance the potential of amphotericin B for renal toxicity, bronchospasm, and hypotension; corticosteroids, digitalis, and thiazides may potentiate hypokalemia; the risk of renal toxicity is increased with cyclosporine
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Monitor renal function, serum electrolytes (eg, magnesium, potassium), liver function, CBC, and hemoglobin concentrations; resume therapy at lowest level (eg, 0.25 mg/kg) when therapy is interrupted for more than 7 d; hypoxemia, acute dyspnea, and interstitial infiltrates may occur in patients with neutropenia who are receiving leukocyte transfusions (separate time of amphotericin infusion from time of leukocyte transfusion); fever and chills are not uncommon after first few administrations; rare acute reactions may include hypotension, bronchospasm, arrhythmias, and shock
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.
Adult
Loading dose: 6 mg/kg IV q12h infused over 2 h for 2 doses
Maintenance: 4 mg/kg IV q12h infused over 2 h; switch to 200 mg PO q12h when able to tolerate; may increase to 300 mg PO q12h if inadequate response
<40 kg: Average maintenance dose is 100 mg PO q12h (may increase to 150 mg PO q12h)
Pediatric
Not established
CYP450 2C19 (highest affinity), 2C9, and 3A4 (minor) substrate and inhibitor; CYP450 inducers (eg, rifampin) have shown to decrease steady state peak plasma levels by up to 93%; may increase serum levels of drugs metabolized by CYP450 2C19 or 2C9, of which some are contraindicated (eg, sirolimus, pimozide, quinidine, cisapride, ergot alkaloids); other drugs may need more frequent monitoring (eg, cyclosporine, tacrolimus, warfarin, HMG-CoA inhibitors, benzodiazepines, calcium channel blockers)
Documented hypersensitivity; CrCl <50 mL/min (decreased excretion of IV vehicle) if administering IV; coadministration with rifampin, rifabutin, carbamazepine, barbiturates, sirolimus, pimozide, quinidine, cisapride, and ergot alkaloids
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Decrease maintenance dose in hepatic dysfunction; common adverse effects include visual disturbances, fever, rash, vomiting, nausea, diarrhea, headache, sepsis, peripheral edema, abdominal pain, rash (including Stevens-Johnson syndrome and phototoxicity), and respiratory disorder; rare cases of severe hepatotoxicity reported; administer PO dosage form 1 h ac or pc
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Further Reading
Keywords
mycetoma, maduromycosis, Madura foot, actinomycetoma, eumycetoma, bacterial mycetoma, fungal mycetoma, actinomycetes, pulmonary mycetoma, mycetoma grain, Pseudallescheria boydii, P boydii, Actinomadura madurae, A madurae, Actinomadura pelletieri, A pelletieri, Streptomyces somaliensis, S somaliensis, Nocardia, Scedosporium apiospermum, S apiospermum, Streptomyces paraguayensis, S paraguayensis, Leptosphaeria, Madurella mycetomatis, M mycetomatis
