Efficacy of carrimycin against Mycobacterium avium complex in vitro and in vivo.

Mycobacterium avium complex (MAC) is one of the principal pathogenic strains among nontuberculous mycobacteria. Current antibiotics have poor microbiological responses, and repurposed antibiotics are a way to meet clinical needs. Herein, the anti-MAC activity of carrimycin (CAM), a new macrolide, was evaluated in vitro and in vivo. Antimicrobial susceptibility testing was performed on two reference strains and 15 clinical isolates of MAC. The synergy between CAM and nine clinically used antibiotics was determined using a checkerboard assay. The activity of CAM against MAC residing inside macrophages and BALB/c mice were also evaluated. Although CAM exhibited weak anti-MAC activity in vitro, with MICs over 8 mg/L, the in vivo activity was potent. CAM treatment significantly reduced bacillary load, alleviated the severity of injury, and improved total T lymphocyte numbers in organs. Additionally, a synergy between CAM and clofazimine was found in vitro and in vivo. No antagonism was found between CAM and other eight antibiotics used in this study. In conclusion, CAM is a potential candidate and should be studied further in clinical trials.IMPORTANCEThe treatment of Mycobacterium avium complex (MAC) infections is a formidable challenge worldwide due to lack of effective drugs. In this paper, we firstly reported a promising candidate drug carrimycin (CAM). For M. intracellulare, the activity of CAM was compared with classical drug azithromycin (AZM). For M. avium, CAM also showed potent activity in vivo. Additionally, the combination of CAM and CFZ reduced more bacillary load than single drugs in vivo. Our study also indicated that we should take pharmacokinetic characteristics and drug interactions into account when evaluating the efficacy of drugs.