Bedaquiline Drug Resistance Emergence Assessment in Multidrug-Resistant Tuberculosis (MDR-TB): a 5-Year Prospective in Vitro Surveillance Study of Bedaquiline and Other Second-Line Drug Susceptibility Testing in MDR-TB Isolates

Koné Kaniga, Rumina Hasan, Ruwen Jou, Edita Vasiliauskienė, Charoen Chuchottaworn, Nazir Ismail, Beverly Metchock, Skaidrius Miliauskas, Nguyen Viet Nhung, Camilla Rodrigues, Soyoun Shin, Hulya Simsek, Saijai Smithtikarn, Anh Le Thi Ngoc, Jirakan Boonyasopun, Mubin Kazi, Seungmo Kim, Phalin Kamolwat, Greta Musteikiene, Catherine Ann SacoponSabira Tahseen, Laima Vasiliauskaitė, Mei Hua Wu, Shaheed Vally Omar

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21 Citations (Scopus)

Abstract

Bedaquiline Drug Resistance Emergence Assessment in Multidrug-resistant tuberculosis (MDR-TB) (DREAM) was a 5-year (2015 to 2019) phenotypic drug resistance surveillance study across 11 countries. DREAM assessed the susceptibility of 5,036 MDR-TB isolates of bedaquiline treatment-naive patients to bedaquiline and other antituberculosis drugs by the 7H9 broth microdilution (BMD) and 7H10/7H11 agar dilution (AD) MIC methods. Bedaquiline AD MIC quality control (QC) range for the H37Rv reference strain was unchanged, but the BMD MIC QC range (0.015 to 0.12 mg/ml) was adjusted compared with ranges from a multilaboratory, multicountry reproducibility study conforming to Clinical and Laboratory Standards Institute Tier-2 criteria. Epidemiological cutoff values of 0.12 mg/ml by BMD and 0.25 mg/ml by AD were consistent with previous bedaquiline breakpoints. An area of technical uncertainty or intermediate category was set at 0.25 mg/ml and 0.5 mg/ml for BMD and AD, respectively. When applied to the 5,036 MDR-TB isolates, bedaquiline-susceptible, -intermediate, and -resistant rates were 97.9%, 1.5%, and 0.6%, respectively, for BMD and 98.8%, 0.8%, and 0.4% for AD. Resistance rates were the following: 35.1% ofloxacin, 34.2% levofloxacin, 33.3% moxifloxacin, 1.5% linezolid, and 2% clofazimine. Phenotypic cross-resistance between bedaquiline and clofazimine was 0.4% in MDR-TB and 1% in pre-extensively drug-resistant (pre-XDR-TB)/XDR-TB populations. Coresistance to bedaquiline and linezolid and clofazimine and linezolid were 0.1% and 0.3%, respectively, in MDR-TB and 0.2% and 0.4%, respectively, in pre-XDR-TB/XDR-TB populations. Resistance rates to bedaquiline appear to be low in the bedaquiline-treatment-naive population. No treatment-limiting patterns for cross-resistance and coresistance have been identified with key TB drugs to date.

Original languageEnglish
Article numbere02919-20
JournalJournal of Clinical Microbiology
Volume60
Issue number1
DOIs
Publication statusPublished - Jan 2022

Keywords

  • Bedaquiline
  • Drug resistance
  • Drug susceptibility testing
  • Mycobacterium tuberculosis
  • Tuberculosis
  • Variants

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