Synergistic activities of tigecycline with clarithromycin or amikacin against rapidly growing mycobacteria in Taiwan

Abstract

The occurrence of diseases caused by rapidly growing mycobacteria (RGM) is increasing in Taiwan. In this study, the in vitro antimicrobial activities of tigecycline, minocycline, tetracycline and doxycycline were evaluated against 160 clinical RGM isolates, including 34 Mycobacterium abscessus sensu stricto (s.s.), 44 Mycobacterium massiliense, 1 Mycobacterium bolletii, 58 Mycobacterium fortuitum and 23 Mycobacterium chelonae. Clarithromycin and amikacin were tested alone as well as for synergistic effect with tigecycline. Both amikacin and tigecycline showed excellent activities against the RGM. More than 85% of each of the five RGM species isolates showed susceptibility to the two drugs. The MIC₅₀ and MIC₉₀ values (drug concentrations at which 50% and 90%, respectively, of the tested isolates did not show any visible growth) of amikacin were 1-4 mg/L and 2-8 mg/L, respectively, whilst those of tigecycline were 0.125-1 mg/L and 0.5-2.0 mg/L. Clarithromycin had only moderate activity, with ≥42.9% but ≤87.5% of each RGM species isolates showing susceptibility. The other three drugs had limited or no antimicrobial activity, with <40% of each RGM species isolates showing susceptibility. Combined with clarithromycin, tigecycline had synergistic activity against 92.9%, 68.8%, 100%, 35.7% and 46.2% of M. abscessus s.s., M. massiliense, M. bolletii, M. fortuitum and M. chelonae isolates, respectively. However, tigecycline combined with amikacin had synergistic activity against <25% but antagonistic activity against >18% of each RGM species. Thus, tigecycline alone may be an alternative for treating RGM diseases in patients who are intolerant to cefoxitin, imipenem or amikacin. However, it should be used with caution or not used in combination with amikacin for RGM diseases.