In vitro activity of aminoglycosides, clofazimine, d-cycloserine and dapsone against 83 Mycobacterium avium complex clinical isolates

Abstract

Background/Purpose: Treatment success rates for Mycobacterium avium complex (MAC) diseases range from 50% to 55% only. To explore effective antimicrobials against either Mycobacterium intracellulare or M. avium, we determined in vitro activities of five aminoglycosides, clofazimine, dapsone and d-cycloserine compared with primary (clarithromycin) and secondary (moxifloxacin and linezolid) antimycobacterial agents. Methods: 83 non-duplicate clinical MAC isolates were collected from sputum and identified at the species level by PCR and restriction enzyme analysis of the 65 kDa hsp and rpoB genes. Drug susceptibility testing was performed using broth microdilution method. The fractional inhibitory concentration was calculated to determine synergy between isepamicin and clofazimine. Results: High susceptibility rates of five aminoglycosides (isepamicin, amikacin, kanamycin, streptomycin, capreomycin, 82.7–88%), d-cycloserine (82.7%), clofazimine (97.3%) and clarithromycin (92%) against M. intracellulare, and 2 aminoglycosides (isepamicin, streptomycin, 87.5%), d-cycloserine (100%) and clarithromycin (100%) against M. avium were found. Dapsone had no inhibitory activity and moxifloxacin had little effect against both M. intracellulare and M. avium. Linezolid had modest activity whereas clofazimine had little effect against M. avium. Most MAC isolates with non-susceptibility to isepamicin were also non-susceptible to the other four aminoglycosides. Most streptomycin-susceptible MAC isolates were also susceptible to amikacin. Synergistic effect of combination of isepamicin and clofazimine was demonstrated in all (100%) M. intracellulare isolates whereas in only 50% M. avium isolates. Conclusion: When treating MAC diseases, species identification plays an important role in choosing treatment regimens. Combination of isepamicin and clofazimine may be a promising regimen in M. intracellulare-associated disease. Keywords: Aminoglycosides, Clofazimine, In vitro activity, Mycobacterium avium complex