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Tianhui Gao,1,* Cong Yao,1,* Yuanyuan Shang,1 Renchun Su,1 Xuxia Zhang,1 Weicong Ren,1 Shanshan Li,1 Wei Shu,2 Yu Pang,1 Qi Li2 1Department of Bacteriology and Immunology, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, People’s Republic of China; 2Clinical Center on Tuberculosis Control, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qi Li; Yu Pang, Beijing Chest Hospital, Capital Medical University, No. 97, Machang, Tongzhou District, Beijing, 101149, People’s Republic of China, Tel/Fax +86 010 6954 6690 ; +86 10 8950 9366, Email lq0703@hotmail.com; pangyupound@163.comPurpose: Unsatisfactory efficacies of currently recommended anti-Mycobacterium abscessus complex (MABC) treatment regimens have led to development of novel drugs to combat MABC infections. In this study, we evaluated in vitro antimicrobial activities of bedaquiline (BDQ) and four oxazolidinones against MABC isolates.Methods: The resazurin microplate assay was performed to determine minimum inhibitory concentrations (MICs) of BDQ and four oxazolidinones, including tedizolid (TZD), sutezolid (SZD), delpazolid (DZD), and linezolid (LZD), against 65 MABC isolates. A checkerboard method was used to investigate efficacies of various antimicrobial drug combinations.Results: BDQ MICs for MABC isolates ranged from < 0.031 to 1 μg/mL, while MIC50 and MIC90 values were 0.125 μg/mL and 0.25 μg/mL, respectively. TZD MIC50 and MIC90 values for MABC isolates were 1 μg/mL and 4 μg/mL, respectively, which were fourfold lower than corresponding LZD values (P < 0.001). DZD MIC90 values for MABC isolates was 8 μg/mL, which were 0.5-fold lower than corresponding LZD values (P < 0.01). MICs of BDQ, SZD, and LZD for M. abscessus subspecies massiliense isolates were significantly lower than corresponding MICs for M. abscessus subspecies abscessus isolates (P < 0.05). Notably, use of oxazolidinones (DZD, SZD, LZD, or TZD) with BDQ against MABC isolates led to reduction of the oxazolidinone median MIC range from 4 to 0.125 μg/mL to 1– 0.031 μg/mL.Conclusion: These results demonstrated excellent BDQ inhibitory activity against MABC isolates. TZD exhibited stronger antimicrobial efficacy against MABC isolates as compared to efficacies of DZD, SZD, and LZD. Importantly, MICs of oxazolidinones were markedly decreased when they were combined with BDQ, thus suggesting that combinations of BDQ and oxazolidinones may be effective treatments for MABC infections.Keywords: bedaquiline, tedizolid, oxazolidinones, susceptibility testing, Mycobacterium abscessus complex, delpazolid |
