Efficacy of carrimycin against <i>Mycobacterium avium</i> complex <i>in vitro</i> and <i>in vivo</i>

<i>Mycobacterium avium</i> complex (MAC) is one of the principal pathogenic strains among nontuberculous <i>mycobacteria</i>. 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 <i>in</i> vitro and <i>in vivo</i>. 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 <i>in vitro</i>, with MICs over 8 mg/L, the <i>in vivo</i> 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 <i>in</i> vitro and in <i>vivo</i>. 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 <i>Mycobacterium avium</i> 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 <i>M. intracellulare</i>, the activity of CAM was compared with classical drug azithromycin (AZM). For <i>M. avium</i>, CAM also showed potent activity <i>in vivo</i>. Additionally, the combination of CAM and CFZ reduced more bacillary load than single drugs <i>in vivo</i>. Our study also indicated that we should take pharmacokinetic characteristics and drug interactions into account when evaluating the efficacy of drugs.