Divergent MIC of Clarithromycin and Azithromycin Against Clinical Isolates of Mycobacterium abscessus Complex

Abstract

Current treatment guidelines for Mycobacterium abscessus complex (MAB) infections recommend macrolides (clarithromycin/CAM and azithromycin/AZM) as cornerstone therapies, considering them clinically interchangeable without distinction. This study evaluated the comparative in vitro activity of clarithromycin (CAM) and azithromycin (AZM) against 146 clinical isolates of Mycobacterium abscessus complex organisms. MIC distributions revealed significantly higher resistance to AZM (94.5% resistant at [≥]8 g/mL) compared to CAM (77.4% resistant at [≥]8 g/mL), with only 4.8% of isolates susceptible to both drugs. Notably, 26 strains (17.8% of total) showed AZM resistance despite being non-resistant to CAM (MIC <8 g/mL) among 146 clinical isolates. Among the 33 CAM-non-resistant isolates (including susceptible and intermediate strains), 78.8% (26/33) were AZM-resistant, demonstrating frequent discordance in susceptibility profiles. These findings contrast with current treatment guidelines that recommend using CAM and AZM interchangeably without distinction. Subspecies analysis showed three distinct susceptibility profiles: isolates susceptible to both antibiotics (n=3, M. massiliense), isolates resistant to both antibiotics (n=3, M. massiliense), and M. bolletii with CAM-susceptible/AZM-resistant phenotypes (n=2). This differential resistance pattern suggests that while both drugs face substantial resistance challenges, CAM retains meaningful activity against certain strains that are AZM-resistant-particularly in M. bolletii. These findings indicate that AZM and CAM should not be used interchangeably to treat MAB infections and emphasize the need to prioritize CAM over AZM in treatment regimens.