Department of Microbiology, The Public Health Agency of Swedengrid.419734.c, Stockholm, Sweden.
Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden.
Antimicrob Agents Chemother. 2021 Aug 17;65(9):e0072021. doi: 10.1128/AAC.00720-21.
Heteroresistance is defined as the coexistence of both susceptible and resistant bacteria in a bacterial population. Previously published data show that it may occur in 9 to 57% of Mycobacterium tuberculosis isolates for various drugs. Pyrazinamide (PZA) is an important first-line drug used for treatment of both drug-susceptible and PZA-susceptible multidrug-resistant TB. Clinical PZA resistance is defined as a proportion of resistant bacteria in the isolate exceeding 10%, when the drug is no longer considered clinically effective. The ability of traditional drug susceptibility testing techniques to detect PZA heteroresistance has not yet been evaluated. The aim of this study was to compare the capacity of Bactec MGIT 960, Wayne's test, and whole-genome sequencing (WGS) to detect PZA-resistant subpopulations in bacterial suspensions prepared with different proportions of mutant strains. Both Bactec MGIT 960 and WGS were able to detect the critical level of 10% PZA heteroresistance, whereas Wayne's test failed to do so, with the latter falsely reporting highly resistant samples as PZA susceptible. Failure to detect drug-resistant subpopulations may lead to inadvertently weak treatment regimens if ineffective drugs are included, with the risk of treatment failure with the selective growth of resistant subpopulations. We need clinical awareness of heteroresistance as well as evaluation of new diagnostic tools for their capacity to detect heteroresistance in TB.
异质性耐药是指在细菌群体中同时存在敏感菌和耐药菌。先前发表的数据表明，各种药物的结核分枝杆菌分离株中，异质性耐药的发生率为 9%至 57%。吡嗪酰胺（PZA）是一种重要的一线药物，用于治疗敏感药物和 PZA 敏感的耐多药结核病。临床 PZA 耐药定义为分离株中耐药菌的比例超过 10%，此时药物不再被认为具有临床疗效。传统药敏检测技术检测 PZA 异质性耐药的能力尚未得到评估。本研究的目的是比较 Bactec MGIT 960、Wayne 试验和全基因组测序（WGS）在不同比例突变株制备的细菌悬浮液中检测 PZA 耐药亚群的能力。Bactec MGIT 960 和 WGS 均能检测到 10% PZA 异质性耐药的临界水平，而 Wayne 试验则未能做到这一点，后者错误地将高度耐药的样本报告为 PZA 敏感。如果包含无效药物，未能检测到耐药亚群可能会导致无意中采用弱治疗方案，而耐药亚群的选择性生长会导致治疗失败的风险。我们需要临床认识到异质性耐药，以及评估新的诊断工具检测 TB 异质性耐药的能力。
