Department of Clinical Microbiology L2:02, Karolinska Institute, Karolinska University Hospital, Stockholm, 171 76, Sweden.
Bull World Health Organ. 2012 Sep 1;90(9):693-8. doi: 10.2471/BLT.11.096644. Epub 2012 May 29.
The rise in multidrug-resistant tuberculosis makes it increasingly important that antimicrobial susceptibility testing of Mycobacterium tuberculosis produce clinically meaningful and technically reproducible results. Unfortunately, this is not always the case because mycobacteriology specialists have not followed generally accepted modern principles for the establishment of susceptibility breakpoints for bacterial and fungal pathogens. These principles specifically call for a definition of the minimum inhibitory concentrations (MICs) applicable to organisms without resistance mechanisms (also known as wild-type MIC distributions), to be used in combination with data on clinical outcomes, pharmacokinetics and pharmacodynamics. In a series of papers the authors have defined tentative wild-type MIC distributions for M. tuberculosis and hope that other researchers will follow their example and provide confirmatory data. They suggest that some breakpoints are in need of revision because they either (i) bisect the wild-type distribution, which leads to poor reproducibility in antimicrobial susceptibility testing, or (ii) are substantially higher than the MICs of wild-type organisms without supporting clinical evidence, which may result in some strains being falsely reported as susceptible. The authors recommend, in short, that susceptibility breakpoints for antituberculosis agents be systematically reviewed and revised, if necessary, using the same modern tools now accepted for all other bacteria and fungi by the scientific community and by the European Medicines Agency and the European Centre for Disease Prevention and Control. For several agents this would greatly improve the accuracy and reproducibility of antimicrobial susceptibility testing of M. tuberculosis.
耐多药结核病的增加使得结核分枝杆菌的抗菌药物敏感性测试产生具有临床意义和技术重现性的结果变得越来越重要。不幸的是，情况并非总是如此，因为分枝杆菌学专家并未遵循公认的现代原则来确定细菌和真菌病原体的药敏折点。这些原则特别要求定义适用于无耐药机制的生物体的最小抑菌浓度 (MIC)（也称为野生型 MIC 分布），并结合临床结果、药代动力学和药效学数据使用。在一系列论文中，作者定义了结核分枝杆菌的暂定野生型 MIC 分布，并希望其他研究人员能够效仿他们并提供确认数据。他们认为，一些折点需要修订，因为它们要么 (i) 将野生型分布一分为二，这导致抗菌药物敏感性测试的重现性较差，要么 (ii) 远高于无临床证据支持的野生型生物体的 MIC，这可能导致一些菌株被错误地报告为敏感。简而言之，作者建议，如果需要，使用目前科学界以及欧洲药品管理局和欧洲疾病预防控制中心接受的所有其他细菌和真菌的相同现代工具，系统地审查和修订抗结核药物的药敏折点。对于几种药物，这将大大提高结核分枝杆菌抗菌药物敏感性测试的准确性和重现性。
