title: In VitroActivity of Bedaquiline against Nontuberculous Mycobacteria in China.
abstract: The main goal of our study was to evaluate thein vitrobedaquiline susceptibility of six prevalent species of pathogenic nontuberculous mycobacteria (NTM) in China. In addition, we investigated the potential molecular mechanisms contributing to bedaquiline resistance in the different NTM species. Among slowly growing mycobacteria (SGM), bedaquiline exhibited the highest activity againstMycobacterium avium; the MIC50and MIC90values were 0.03 and 16 mg/liter, respectively. Among rapidly growing mycobacteria (RGM),Mycobacterium abscessussubsp.abscessus(M. abscessus) andMycobacterium abscessussubsp.massiliense(M. massiliense) seemed more susceptible to bedaquiline thanMycobacterium fortuitum, with MIC50and MIC90values of 0.13 and >16 mg/liter, respectively, for both species. On the basis of bimodal distributions of bedaquiline MICs, we proposed the following epidemiological cutoff (ECOFF) values: 1.0 mg/liter for SGM and 2.0 mg/liter for RGM. AmongM. avium,Mycobacterium intracellulare,Mycobacterium kansasii,M. abscessus,M. massiliense, andM. fortuitumisolates, 14 (29.8%), 41 (27.2%), 33 (39.3%), 44 (20.2%), 42 (25.8%), and 7 (31.8%), respectively, were resistant to bedaquiline. No significant differences in the proportions of bedaquiline resistance among these species were observed (P> 0.05). Genetic mutations were observed in 74 isolates (10.8%), with all nucleotide substitutions being synonymous. In conclusion, our data demonstrate that bedaquiline shows moderatein vitroactivity against NTM species. Using the proposed ECOFF values, we could distinguish between bedaquiline-resistant and -susceptible strains with the broth dilution method. In addition, no nonsynonymous mutations in theatpEgene that conferred bedaquiline resistance in all six NTM species were identified.
authors.affiliation: National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory on Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China pangyupound@163.com zhaoyanlin@chinatb.org.
authors.forename: Yu
authors.identifier: 0000-0002-4425-9124
authors.initials: Y
authors.lastname: Pang
authors.affiliation: National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: Huiwen
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Clinical Laboratory, Guangzhou Chest Hospital, Guangdong Province, Guangzhou, China.
authors.forename: Yaoju
authors.initials: Y
authors.lastname: Tan
authors.affiliation: National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Song
authors.affiliation: National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China pangyupound@163.com zhaoyanlin@chinatb.org.
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D025243:Bacterial Proton-Translocating ATPases / Q000235:genetics; D064687:Diarylquinolines / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation / Q000235:genetics; D009165:Mycobacterium Infections, Nontuberculous / Q000188:drug therapy* / Q000382:microbiology; D009170:Nontuberculous Mycobacteria / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D012336:RNA, Ribosomal, 16S / Q000235:genetics
chemical_list: D000995:Antitubercular Agents; D064687:Diarylquinolines; D012336:RNA, Ribosomal, 16S; C493870:bedaquiline; D025243:Bacterial Proton-Translocating ATPases
keywords: ECOFF; bedaquiline; nontuberculous mycobacteria