Wang Zimo, Li Xiaodong, Zhang Weiyan, Fu Lei, Li Xinda, Chen Xiaoyou, Lu Yu
Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.
Beijing Ditan Hospital, Capital Medical University, Beijing, China.
Microbiol Spectr. 2025 Sep 2;13(9):e0242224. doi: 10.1128/spectrum.02422-24. Epub 2025 Aug 8.
complex (MAC) is one of the principal pathogenic strains among nontuberculous . 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 vitro and . 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 , with MICs over 8 mg/L, the 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 vitro and in . 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 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 , the activity of CAM was compared with classical drug azithromycin (AZM). For , CAM also showed potent activity . Additionally, the combination of CAM and CFZ reduced more bacillary load than single drugs . Our study also indicated that we should take pharmacokinetic characteristics and drug interactions into account when evaluating the efficacy of drugs.
鸟分枝杆菌复合体（MAC）是非结核分枝杆菌中的主要致病菌株之一。目前的抗生素微生物学反应较差，重新利用的抗生素是满足临床需求的一种途径。在此，评估了一种新型大环内酯类药物卡里霉素（CAM）对MAC的体外抗菌活性。对两株参考菌株和15株MAC临床分离株进行了药敏试验。采用棋盘法测定了CAM与9种临床常用抗生素之间的协同作用。还评估了CAM对巨噬细胞内和BALB/c小鼠体内MAC的活性。尽管CAM表现出较弱的抗MAC活性，最低抑菌浓度超过8mg/L，但其细胞内活性较强。CAM治疗显著降低了细菌载量，减轻了损伤严重程度，并提高了器官中总T淋巴细胞数量。此外，在体外和体内均发现CAM与氯法齐明之间存在协同作用。在本研究中，未发现CAM与其他8种抗生素之间存在拮抗作用。总之，CAM是一个潜在的候选药物，应在临床试验中进一步研究。重要性由于缺乏有效药物，全球范围内治疗鸟分枝杆菌复合体（MAC）感染是一项艰巨的挑战。在本文中，我们首次报道了一种有前景的候选药物卡里霉素（CAM）。在体外，将CAM的活性与经典药物阿奇霉素（AZM）进行了比较。在体内，CAM也表现出较强的活性。此外，CAM与CFZ联合使用比单一药物降低了更多的细菌载量。我们的研究还表明，在评估药物疗效时应考虑药代动力学特征和药物相互作用。
