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.
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.
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DOI：
10.1128/jcm.02919-20
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发表时间：
2022-01-19
影响因子：
9.4
通讯作者：
Vally Omar S
中科院分区：
文献类型：
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作者：
Kaniga K;Hasan R;Jou R;Vasiliauskienė E;Chuchottaworn C;Ismail N;Metchock B;Miliauskas S;Viet Nhung N;Rodrigues C;Shin S;Simsek H;Smithtikarn S;Ngoc ALT;Boonyasopun J;Kazi M;Kim S;Kamolwat P;Musteikiene G;Sacopon CA;Tahseen S;Vasiliauskaitė L;Wu MH;Vally Omar S
多药耐药结核病(MDR-TB)的贝达奎林耐药显现评估(DREAM)是一项为期5年(2015至2019年)的表型耐药性监测研究，涉及11个国家。DREAM通过7H9肉汤微量稀释(BMD)和7H10/7H11琼脂稀释(AD)最低抑菌浓度(MIC)方法评估了5036株贝达奎林治疗初期患者对贝达奎林和其他抗结核药物的敏感性。H37Rv参考菌株的贝达奎林AD MIC质量控制(QC)范围没有变化，但与符合临床和实验室标准协会Tier-2标准的多实验室、多国家重复性研究的范围相比，BMDMIC QC范围(0.015至0.12MIC g/ml)进行了调整。BMD和AD的流行病学临界值分别为0.12 μg/ml和0.25 μg/ml，与先前的贝达奎林临界值一致。将骨密度和AD的技术不确定区或中间类别分别设定为0.25 μg/ml和0.5 μg/ml。在5,036株耐多药结核分枝杆菌中，对贝达奎林敏感、中间和耐药的BMD分别为97.9%、1.5%和0.6%，AD分别为98.8%、0.8%和0.4%。耐药率依次为：氧氟沙星35.1%、左氧氟沙星34.2%、莫西沙星33.3%、利奈唑胺1.5%、氯法齐明2%。在耐多药结核病中，贝达奎林和氯法齐明的表型交叉耐药性为0.4%，在广泛耐药(广泛耐药前)/广泛耐药结核病人群中为1%。MDR-TB对贝达奎林、利奈唑胺和氯法齐明、利奈唑胺的耐药率分别为0.1%和0.3%，XDR-TB/XDR-TB前期人群分别为0.2%和0.4%。在贝达奎兰治疗的幼稚人群中，对贝达奎兰的耐药率似乎很低。到目前为止，尚未在关键的结核病药物中确定交叉耐药和共同耐药的治疗限制模式。
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 μg/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 μg/ml by BMD and 0.25 μg/ml by AD were consistent with previous bedaquiline breakpoints. An area of technical uncertainty or intermediate category was set at 0.25 μg/ml and 0.5 μg/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.