Efficacy of imipenem therapy for Nocardia actinomycetomas refractory to sulfonamides

Background

Actinomycetomas are chronic, granulomatous, subcutaneous infections caused by actinomycetes bacteria. Despite prolonged high-dose and combination antibiotic therapies, some cases remain resistant with risks of bone and visceral involvement.

Objectives

We sought to evaluate the efficacy and safety of imipenem monotherapy, and in combination with amikacin for the treatment of severe and refractory disease, and to identify the disease characteristics that might predict therapy failure with first-line sulfonamides.

Methods

A retrospective study was performed of all microbiologically confirmed cases of actinomycetomas treated since 1995 at a tertiary center for mycology. Eleven patients (Nocardia, n = 10) were treated with sulfonamide combinations (trimethoprim/sulfamethoxazole and dapsone). Eight patients (Nocardia, n = 7) refractory to previous therapies including sulfonamides received a 3-week course of either parenteral imipenem monotherapy (1.5 g daily, n = 3) or combination therapy with amikacin (1 g daily, n = 5), which was repeated at 6-month intervals.

Results

Eleven patients with limited disease and mean disease duration of 1.7 years responded successfully to sulfonamides after a mean treatment period of 15 months (range 6-48 months). Patients receiving imipenem had mean disease duration of 10 years, with visceral and bone involvement in 4 patients. Imipenem treatment was well tolerated, and 4 patients achieved clinical and microbiological cure after one to two courses of treatment, the others demonstrating greater than 75% clinical improvement and negative culture results.

Limitations

Patient cohorts in this study were small because strict criteria for inclusion included species identification and adequate follow-up periods. The efficacy data for imipenem ± amikacin therapy cannot be extrapolated to all Nocardia mycetomas, as the cohort treated in this study had particularly refractory infection.

Conclusions

Sulfonamides are effective for limited disease of relatively short duration. Imipenem monotherapy or in combination with amikacin is well tolerated and demonstrates efficacy in severe disease refractory to sulfonamides.

Key words: actinomycetoma, amikacin, imipenem, Nocardia, sulfonamide

Abbreviations used: DDS, dapsone, SMX, sulfamethoxazole, TMP, trimethoprim