eMedicine Specialties > Dermatology > Fungal Infections
Mycetoma: Treatment & Medication
Updated: Mar 26, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
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Treatment
Medical Care
- Eumycetoma
- 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.12,13 Therapy is suggested for 1-2 years (or greater) for complete eradication, unless adverse effects warrant cessation of medication.
- In 2 cases, the authors have used a combination of itraconazole and terbinafine resulting in the remission of the disease.14 Surgical treatment remains a viable therapy for mycetoma caused by fungi.
- Actinomycetoma
- The current treatment of actinomycetoma is trimethoprim-sulfamethoxazole 7.5-40 mg/kg daily in 3 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 daily should be added.15 Every 2 or 3 weeks, a periodic audiometric and creatine clearance analysis must be performed. This treatment is maintained for 5-15 weeks and, in some cases for a longer period of time, depending on the clinical response and renal and auditory adverse effects.
- Netilmicin can be used in cases resistant to amikacin. Other antimicrobials, such as minocycline, amoxicillin-clavulanic acid, streptomycin, imipenem, and rifampin, have also been used with variable success.16 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 are active in vitro and in experimental models of N brasiliensis infection, although they have not been used in humans.
- 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 its utility in human cases.17,18
Surgical Care
- In eumycetoma, surgical treatment is a therapeutic option if the patient's condition has not responded to medical treatment alone. In these cases, both modalities are typically used.
- Surgical treatment, including amputation, for actinomycetoma is seldom indicated.
Medication
The goals of pharmacotherapy are to reduce morbidity, to prevent complications, and to eradicate the disease.
Antifungals
Ketoconazole, itraconazole, amphotericin B, and terbinafine are most commonly used to treat mycetoma. When systemic agents are administered, monitoring patients for adverse effects and complications common to the drug is important. Therapy is suggested for 1-2 years (or greater) for complete eradication, unless adverse effects warrant cessation of medication.
Ketoconazole (Nizoral)
Imidazole broad-spectrum antifungal agent; inhibits synthesis of ergosterol, causing cellular components to leak and resulting in fungal cell death. Available in 200-mg tab.
Adult
400 mg PO qd
Pediatric
Not established
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 (avoided with dose of 200-400 mg/d); administer antacid, anticholinergics, or H2-blockers at least 2 h after taking ketoconazole
Itraconazole (Sporanox)
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. Available in 100-mg cap.
Adult
200-400 mg PO qd
Pediatric
Not established
Increased level of cyclosporine, tacrolimus, and digoxin may occur after coadministration; phenytoin and rifampin may decrease effect; coadministration with amlodipine or nifedipine may cause edema; hypoglycemia was observed after coadministration with sulfonylureas; avoid alcohol use because disulfiramlike reactions may occur; antacids may reduce absorption; coadministration with terfenadine (recalled from US market), astemizole (recalled from US market), lovastatin, simvastatin, cisapride, triazolam, and midazolam
Serious cardiovascular events, including death, were reported in patients treated with itraconazole and H1-receptor inhibitors (terfenadine, astemizole); coadministration with cisapride may cause arrhythmia; coadministration with triazolam and midazolam may increase their plasma levels; rhabdomyolysis may occur with coadministration of HMG-CoA reductase inhibitors (lovastatin, simvastatin)
Documented hypersensitivity; coadministration of terfenadine, astemizole, or cisapride (itraconazole cap); concomitant administration with oral triazolam or with oral midazolam; administration for treatment of onychomycosis to pregnant patients or to women contemplating pregnancy
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 (AmBisome)
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.
Adult
50 mg IV qd
Pediatric
Not established
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 count, and hemoglobin concentrations; resume therapy at the lowest level (eg, 0.25 mg/kg) when therapy is interrupted for > 7 d; hypoxemia, acute dyspnea, and interstitial infiltrates may occur in patients with neutropenia receiving leukocyte transfusions (separate time of amphotericin infusion from time of leukocyte transfusion)
Terbinafine (Lamisil)
Inhibits squalene epoxidase, which decreases ergosterol synthesis, causing fungal cell death. Use medication until symptoms significantly improve.
Adult
250 mg/d PO
Pediatric
Not established
May decrease cyclosporine effects; may increase toxicity with rifampin and cimetidine
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Discontinue use if chemical irritation or signs of hepatobiliary dysfunction develop
Antibiotics
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.
Trimethoprim and sulfamethoxazole (Bactrim, Bactrim DS, Septra, Septra DS)
Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. In certain anatomical sites (eg, thorax, head), extensive lesions, and cases recalcitrant to this antibiotic, add amikacin and maintain for 5-15 wk (or longer), depending on clinical response and renal and auditory adverse effects.
Adult
7.5-40 mg/kg PO tid for several months or years
Septra DS or Bactrim DS: 1 tab bid
Pediatric
Not established
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 persons; 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
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
Discontinue at first appearance of skin rash or sign of adverse reaction; obtain CBC counts frequently; discontinue therapy if significant hematologic changes occur; goiter, diuresis, and hypoglycemia may occur with sulfonamides; 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, persons with chronic alcoholism, elderly persons, those receiving anticonvulsant therapy, those with malabsorption syndrome); hemolysis may occur in persons with G-6-PD deficiency; 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; causes growth inhibition. Use the patient's IBW for dosage calculation. The current treatment of actinomycetoma is every 2 or 3 wk. Periodic audiometric and CrCl testing must be performed.
Adult
15 mg/kg/d IM divided bid/tid; not to exceed 1.5 g/d
Pediatric
Not established
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
Netilmicin (Netromycin)
For gram-negative bacterial coverage of infections resistant to gentamicin. Irreversibly binds to 30S subunit of bacterial ribosomes; blocks recognition step in protein synthesis; causes growth inhibition.
Use IBW for dose calculation.
Adult
1.5-2 mg/kg IV/IM q12h (3-4 mg/kg/d)
Pediatric
Not established
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
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
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
Minocycline (Dynacin, Minocin)
Treats infections caused by susceptible gram-negative and gram-positive organisms, in addition to infections caused by susceptible Chlamydia, Rickettsia, and Mycoplasma species.
Adult
100 mg PO bid
Pediatric
<8 years: Not recommended
>8 years: 4 mg/kg PO initially, followed with 2 mg/kg q12h
Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can increase hypoprothrombinemic effects of anticoagulants
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 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines
Amoxicillin and clavulanate (Augmentin)
Drug combination treats bacteria resistant to beta-lactam antibiotics. Indicated for skin and skin structure infections caused by beta-lactamase–producing strains of Staphylococcus aureus. For children >3 mo, dose on amoxicillin content. Because of different amoxicillin/clavulanic acid ratios in 250-mg tab (250/125) vs 250-mg chewable tab (250/62.5), do not use 250-mg tab until child weighs >40 kg.
Adult
500 mg PO q12h or 250 mg PO q8h
Pediatric
<40 kg: 20-40 mg/kg/d PO divided bid
>40 kg: Administer as in adults
Coadministration with warfarin or heparin increases risk of bleeding
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Anaphylactic reactions have been reported and are more common with a prior history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens or cephalosporins
Streptomycin
Aminoglycoside antibiotic recommended when less potentially hazardous therapeutic agents are ineffective or contraindicated.
Adult
1 g IM qd; 15 mg/kg/d IM 2 times/wk; not to exceed 1 g/d; 25-30 mg/kg/d IM 3 times/wk; not to exceed 1.5 g/d
Pediatric
20-40 mg/kg/d IM 2 times/wk; not to exceed 1 g/d; 25-30 mg/kg/d IM 3 times/wk; not to exceed 1.5 g/d
Nephrotoxicity may be increased with aminoglycosides, cephalosporins, penicillins, amphotericin B, and loop diuretics
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); caution with myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission
Imipenem and cilastatin (Primaxin)
For treatment of multiple organism infections in which other agents do not have wide spectrum coverage or are contraindicated because of potential for toxicity.
Adult
Base initial dose on severity of infection, and administer in equally divided doses; dose may range from 250-500 mg IV q6h for a maximum of 3-4 g/d
Alternatively, 500-750 mg IM or intra-abdominally q12h
Pediatric
>3 months: 15-25 mg/kg/dose IV q6h; do not exceed 2 g/d if fully susceptible organisms; for moderately susceptible organisms, do not exceed 4 g/d
Coadministration with cyclosporine may increase CNS adverse 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
Rifampin (Rifadin, Rimactane)
Inhibits DNA-dependent bacterial but not mammalian RNA polymerase. Supplied as 150- or 300-mg cap. Rifampin for injection USP contains rifampin 600 mg, sodium formaldehyde sulfoxylate 10 mg, and sodium hydroxide to adjust pH to 7.8-8.8. Rifampin for injection is for IV infusion only.
Adult
600 mg PO/IV qd
Pediatric
10-20 mg/kg PO/IV; 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, 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
Obtain CBC counts 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; body fluids (tears, saliva, urine) and feces may turn red-orange during therapy and patients should be warned of this side effect
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| Differential Diagnoses & Workup: Mycetoma |
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References
Welsh O, Vera-Cabrera L, Salinas-Carmona MC. Mycetoma. Clin Dermatol. Mar-Apr 2007;25(2):195-202. [Medline].
Solis-Soto JM, Quintanilla-Rodriguez LE, Meester I, et al. In situ detection and distribution of inflammatory cytokines during the course of infection with Nocardia brasiliensis. Histol Histopathol. May 2008;23(5):573-81. [Medline].
Salinas-Carmona MC, Perez-Rivera I. Humoral immunity through immunoglobulin M protects mice from an experimental actinomycetoma infection by Nocardia brasiliensis. Infect Immun. Oct 2004;72(10):5597-604. [Medline].
Lopez Martinez R, Mendez Tovar LJ, Lavalle P, Welsh O, Saul A, Macotela Ruiz E. [Epidemiology of mycetoma in Mexico: study of 2105 cases]. Gac Med Mex. Jul-Aug 1992;128(4):477-81. [Medline].
van de Sande WW, Fahal A, Verbrugh H, van Belkum A. Polymorphisms in genes involved in innate immunity predispose toward mycetoma susceptibility. J Immunol. Sep 1 2007;179(5):3065-74. [Medline].
Kashima M, Kano R, Mikami Y, et al. A successfully treated case of mycetoma due to Nocardia veterana. Br J Dermatol. Jun 2005;152(6):1349-52. [Medline].
Rodriguez-Nava V, Couble A, Molinard C, Sandoval H, Boiron P, Laurent F. Nocardia mexicana sp. nov., a new pathogen isolated from human mycetomas. J Clin Microbiol. Oct 2004;42(10):4530-5. [Medline].
Brown-Elliott BA, Brown JM, Conville PS, Wallace RJ Jr. Clinical and laboratory features of the Nocardia spp. based on current molecular taxonomy. Clin Microbiol Rev. Apr 2006;19(2):259-82. [Medline].
Desnos-Ollivier M, Bretagne S, Dromer F, Lortholary O, Dannaoui E. Molecular identification of black-grain mycetoma agents. J Clin Microbiol. Oct 2006;44(10):3517-23. [Medline].
Salinas-Carmona MC, Welsh O, Casillas SM. Enzyme-linked immunosorbent assay for serological diagnosis of Nocardia brasiliensis and clinical correlation with mycetoma infections. J Clin Microbiol. Nov 1993;31(11):2901-6. [Medline].
Vera-Cabrera L, Salinas-Carmona MC, Welsh O, Rodriguez MA. Isolation and purification of two immunodominant antigens from Nocardia brasiliensis. J Clin Microbiol. May 1992;30(5):1183-8. [Medline].
Lacroix C, de Kerviler E, Morel P, Derouin F, Feuilhade de Chavin M. Madurella mycetomatis mycetoma treated successfully with oral voriconazole. Br J Dermatol. May 2005;152(5):1067-8. [Medline].
Negroni R, Tobon A, Bustamante B, Shikanai-Yasuda MA, Patino H, Restrepo A. Posaconazole treatment of refractory eumycetoma and chromoblastomycosis. Rev Inst Med Trop Sao Paulo. Nov-Dec 2005;47(6):339-46. [Medline].
N'diaye B, Dieng MT, Perez A, Stockmeyer M, Bakshi R. Clinical efficacy and safety of oral terbinafine in fungal mycetoma. Int J Dermatol. Feb 2006;45(2):154-7. [Medline].
Welsh O, Sauceda E, Gonzalez J, Ocampo J. Amikacin alone and in combination with trimethoprim-sulfamethoxazole in the treatment of actinomycotic mycetoma. J Am Acad Dermatol. Sep 1987;17(3):443-8. [Medline].
Fuentes A, Arenas R, Reyes M, Fernandez RF, Zacarias R. [Actinomycetoma and Nocardia sp. Report of five cases treated with imipenem or imipenem plus amikacin]. Gac Med Mex. May-Jun 2006;142(3):247-52. [Medline].
Vera-Cabrera L, Daw-Garza A, Said-Fernandez S, et al. Therapeutic Effect of a Novel Oxazolidinone, DA-7867, in BALB/c Mice Infected with Nocardia brasiliensis. PLoS Negl Trop Dis. Sep 10 2008;2(9):e289. [Medline].
Chacon-Moreno BE, Welsh O, Cavazos-Rocha N, et al. Efficacy of ciprofloxacin and moxifloxacin against Nocardia brasiliensis in vitro and in an experimental model of actinomycetoma in BALB/c mice. Antimicrob Agents Chemother. Jan 2009;53(1):295-7. [Medline].
Hay RJ, Mahgoub ES, Leon G, al-Sogair S, Welsh O. Mycetoma. J Med Vet Mycol. 1992;30 Suppl 1:41-9. [Medline].
Mahgoub ES, Murray IG. Mycetoma. London, England: William Heinemann; 1973:76-115.
Mariat F, Destombes P, Segretain G. The mycetomas: clinical features, pathology, etiology and epidemiology. Contrib Microbiol Immunol. 1977;4:1-39. [Medline].
van de Sande WW, Janse DJ, Hira V, et al. Translationally controlled tumor protein from Madurella mycetomatis, a marker for tumorous mycetoma progression. J Immunol. Aug 1 2006;177(3):1997-2005. [Medline].
Vera-Cabrera L, Gonzalez E, Rendon A, et al. In vitro activities of DA-7157 and DA-7218 against Mycobacterium tuberculosis and Nocardia brasiliensis. Antimicrob Agents Chemother. Sep 2006;50(9):3170-2. [Medline].
Welsh O. Mycetoma. Current concepts in treatment. Int J Dermatol. Jun 1991;30(6):387-98. [Medline].
Further Reading
Keywords
mycetoma, Madura foot, maduromycosis, actinomycetoma, eumycetoma, Nocardia species, Actinomadura species, Streptomyces species, Nocardiopsis species, Nocardia brasiliensis, N brasiliensis, Actinomadura madurae, A madurae, Madurella mycetomatis, M mycetomatis, Streptomyces somaliensis, S somaliensis, Actinomadura pelletieri, A pelletieri
