Activities of Moxifloxacin in Combination with Macrolides against Clinical Isolates of Mycobacterium abscessus and Mycobacterium massiliense
ABSTRACTInfections caused byMycobacterium abscessusandMycobacterium massilienseare on the rise among humans. Although macrolides, including clarithromycin (CLR) and azithromycin (AZM), are key antibiotics for the treatment ofM. abscessusandM. massilienseinfections, treatment regimens for these infections are still largely undefined. In this study, we evaluated thein vitro,ex vivo, andin vivoactivities of moxifloxacin (MXF) in combination with macrolides against clinically isolatedM. abscessusandM. massiliensestrains. Overall, CLR, AZM, and MXF alone showed activity against both speciesin vitro,ex vivo, andin vivo. When MXF was combined with a macrolide againstM. abscessusisolates, antagonism was observed in 65.4% (17/26) of the strains with CLR and 46.2% (12/26) of the strains with AZMin vitroas well as in 66.7% (10/15) of the strains with CLR and 40.0% (6/15) of the strains with AZM in macrophages as determined by the fractional inhibitory concentration index. In contrast, either indifferent or synergistic effects of the MXF-macrolide combinations were observed against onlyM. massiliensestrains. Moreover, a murine infection model showed similar results. Antagonism between the MXF and macrolide combinations was observed in five out of sevenM. abscessusstrains, while indifferent and synergistic effects for these combinations were observed for three of the sixM. massiliensestrains tested, respectively. In conclusion, the activity of MXF in combination with a macrolide differed forM. abscessusandM. massilienseinfections and the addition of MXF to macrolide therapy had no benefit for the treatment ofM. abscessusinfections.