Efficacy of regimens targeting Mycobacterium abscessus in vitro and in vivo

BACKGROUND: M. abscessus (Mabs) is one of the principal pathogenic strains among nontuberculous mycobacterial. Mabs infections pose a significant global public health challenge, leading to substantial morbidity and mortality. However, a standard treatment regimen has not yet been established. The goal of this study was to provide clear insights into constructing regimens. METHODS: We evaluated the efficacy of 7 clinically available drugs against Mabs under various environments through microplate alamar blue assay (MABA), biofilm assays, Wayne model and nutrient-starvation model. The checkerboard assay was employed to assess drug-drug interactions. Finally, we assessed the efficacy, degree of organ damage, and prevalence of resistant strains associated with different triple-drug combinations in a BALB/c mouse model. RESULTS: Bedaquiline (BDQ) was active against replicating and nonreplicating planktonic bacteria. Moxifloxacin (MFX) was potent in preventing biofilm formation and inhibiting the viability of biofilm-resident bacteria. ABM (Azithromycin-Bedaquiline-Moxifloxacin) and CBM (Clofazimine-Bedaquiline-Moxifloxacin) combinations were effective in bacillary load reduction and organ injury alleviation in BALB/c mouse model. CONCLUSIONS: ABM and CBM regimens show great promise against Mabs in vivo. We strongly recommend carrying out additional clinical trials to explore their efficacy.