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

ABSTRACT 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. IMPORTANCE The 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.