In vitro activity of clarithromycin in combination with other antimicrobial agents against Mycobacterium abscessus and Mycobacterium massiliense

Abstract Macrolides, especially clarithromycin (CLA), remain the cornerstone of therapy for Mycobacterium abscessus complex infections. The purpose of this study was to gather results from in vitro drug susceptibility testing of M. abscessus and Mycobacterium massiliense for the combination of CLA with various other agents, including linezolid (LZD), moxifloxacin (MOX), amikacin (AMK) and tigecycline (TGC). A total of 40  M. abscessus complex isolates were studied, comprising 20  M. abscessus and 20  M. massiliense strains. In vitro drug susceptibility testing revealed that the percentage of TGC-resistant isolates among M. massiliense was significantly lower than that among M. abscessus ( P  = 0.047). In addition, 17 (85.0%) of 20  M. massiliense isolates showed a synergistic effect for the CLA + MOX combination, which was significantly higher than for M. abscessus (1/20; 5.0%) ( P  0.001). Similarly, synergy for the CLA + TGC combination was found in 5 (25.0%) M. abscessus isolates and 13 (65.0%) M. massiliense isolates, with a significant difference between the two subspecies ( P  = 0.038). For CLA + LZD and CLA + AMK combinations, statistical analysis demonstrated that there was no significant difference in the proportion of synergistic effect between the two subspecies ( P  > 0.05). In conclusion, these data demonstrate that M. abscessus and M. massiliense exhibit significant differences in TGC susceptibility. In addition, the activity of CLA in combination with MOX or TGC showed better synergistic activity against M. massiliense than against M. abscessus .