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Bedaquiline resistance pattern in clofazimine-resistant clinical isolates of tuberculosis patients.
Shang, Yuanyuan; Chen, Suting; Shi, Wenhui; Nie, Wenjuan; Jing, Wei; Huo, Fengmin; Xue, Yi; Dong, Lingling; Jiang, Guanglu; Huang, Hairong; Chu, Naihui.
Afiliação
  • Shang Y; Tuberculosis Department, Beijing Chest Hospital, Capital Medical University, Beijing, China; National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug Resistant Tuberculosis Research; Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Inst
  • Chen S; National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug Resistant Tuberculosis Research; Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China.
  • Shi W; Tuberculosis Department, Beijing Chest Hospital, Capital Medical University, Beijing, China.
  • Nie W; Tuberculosis Department, Beijing Chest Hospital, Capital Medical University, Beijing, China.
  • Jing W; Tuberculosis Department, Beijing Chest Hospital, Capital Medical University, Beijing, China.
  • Huo F; National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug Resistant Tuberculosis Research; Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China.
  • Xue Y; National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug Resistant Tuberculosis Research; Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China.
  • Dong L; National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug Resistant Tuberculosis Research; Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China.
  • Jiang G; National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug Resistant Tuberculosis Research; Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China.
  • Huang H; National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug Resistant Tuberculosis Research; Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China. Electronic address: huanghairong@tb123.org.
  • Chu N; Tuberculosis Department, Beijing Chest Hospital, Capital Medical University, Beijing, China. Electronic address: dongchu1994@sina.com.
J Glob Antimicrob Resist ; 33: 294-300, 2023 06.
Article em En | MEDLINE | ID: mdl-37142094
OBJECTIVES: Bedaquiline (BDQ) is a potent drug for treating drug-resistant tuberculosis (TB). Here, we analysed the resistance profiles of BDQ in CFZ-resistant clinical isolates and investigated the clinical risk factors of BDQ and CFZ cross/co-resistance. METHODS: The AlarmarBlue microplate assay was performed to determine the minimum inhibitory concentration (MIC) of the CFZ-resistant Mycobacterium tuberculosis (MTB) clinical isolates to CFZ and BDQ. The clinical characteristics of the respective patients were analysed to explore the possible risk factors of BDQ resistance. The drug-resistance-associated genes including Rv0678, Rv1979c, atpE, pepQ and Rv1453 were sequenced and analysed. RESULTS: A total of 72 clinical CFZ-resistant MTB isolates were collected; among these, half were identified as BDQ-resistant. The MIC value of BDQ closely correlated with CFZ (Spearman's q = 0.766, P < 0.005). Among the isolates with a MIC of CFZ ≥4 mg/L, 92.31% (12/13) were resistant to BDQ. Pre-XDR and exposure to BDQ or CFZ are the major risk factors for concurrent BDQ resistance. Among the 36 cross/co-resistant isolates, 50% (18/36) had mutations in Rv0678, 8.3% (3/36) had mutations in Rv0678+Rv1453, 5.6% (2/36) had mutations in Rv0678+Rv1979c, 2.8% (1/36) had mutations in Rv0678+Rv1979c+Rv1453, 2.8% (1/36) had mutations in atpE+Rv0678+Rv1453, 2.8% (1/36) had mutations in Rv1979c, and 27.7% (10/36) had no variations in the target genes. CONCLUSION: Nearly half of the CFZ-resistant isolates were still sensitive to BDQ, whereas this rate dramatically decreased among patients with pre-XDR TB or those who had been exposed to BDQ or CFZ.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tuberculose / Clofazimina Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: J Glob Antimicrob Resist Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tuberculose / Clofazimina Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: J Glob Antimicrob Resist Ano de publicação: 2023 Tipo de documento: Article