Synergistic and additive effects of rifampicin, moxifloxacin, ethambutol, and azithromycin against M. simiae clinical isolates.

Pulmonary disease caused by Mycobacterium simiae is challenging to treat due to intrinsic resistance and limited guidelines. We assessed synergy among rifampicin, moxifloxacin, ethambutol, and azithromycin using the checkerboard method. Synergy (FICI = 0.5) was found only for the moxifloxacin-ethambutol combination in 63% of 27 clinical isolates, with the remainder showing additive effects. No synergy was observed for rifampicin or azithromycin. These findings suggest potential therapeutic benefit for the moxifloxacin-ethambutol combination, even in non-susceptible isolates, supporting reconsideration of ethambutol in treatment regimens. Clinical studies are needed to validate the observed in vitro synergy.