Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas.
Center for Tuberculosis Research, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Clin Infect Dis. 2015 Aug 15;61 Suppl 1:S10-7. doi: 10.1093/cid/civ425.
The in vitro hollow fiber system model of tuberculosis (HFS-TB), in tandem with Monte Carlo experiments, was introduced more than a decade ago. Since then, it has been used to perform a large number of tuberculosis pharmacokinetics/pharmacodynamics (PK/PD) studies that have not been subjected to systematic analysis.
We performed a literature search to identify all HFS-TB experiments published between 1 January 2000 and 31 December 2012. There was no exclusion of articles by language. Bias minimization was according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Steps for reporting systematic reviews were followed.
There were 22 HFS-TB studies published, of which 12 were combination therapy studies and 10 were monotherapy studies. There were 4 stand-alone Monte Carlo experiments that utilized quantitative output from the HFS-TB. All experiments reported drug pharmacokinetics, which recapitulated those encountered in humans. HFS-TB studies included log-phase growth studies under ambient air, semidormant bacteria at pH 5.8, and nonreplicating persisters at low oxygen tension of ≤ 10 parts per billion. The studies identified antibiotic exposures associated with optimal kill of Mycobacterium tuberculosis and suppression of acquired drug resistance (ADR) and informed predictions about optimal clinical doses, expected performance of standard doses and regimens in patients, and expected rates of ADR, as well as a proposal of new susceptibility breakpoints.
The HFS-TB model offers the ability to perform PK/PD studies including humanlike drug exposures, to identify bactericidal and sterilizing effect rates, and to identify exposures associated with suppression of drug resistance. Because of the ability to perform repetitive sampling from the same unit over time, the HFS-TB vastly improves statistical power and facilitates the execution of time-to-event analyses and repeated event analyses, as well as dynamic system pharmacology mathematical models.
体外中空纤维结核模型（HFS-TB）与蒙特卡罗实验一起，于十多年前被引入。从那时起，它已被用于进行大量的结核病药代动力学/药效学（PK/PD）研究，但这些研究并未进行系统分析。
我们进行了文献检索，以确定 2000 年 1 月 1 日至 2012 年 12 月 31 日期间发表的所有 HFS-TB 实验。不排除按语言发表的文章。根据系统评价和荟萃分析的首选报告项目（PRISMA），尽量减少偏差。按照系统评价报告的步骤进行。
共发表了 22 项 HFS-TB 研究，其中 12 项为联合治疗研究，10 项为单药治疗研究。有 4 项独立的蒙特卡罗实验利用了 HFS-TB 的定量输出。所有实验均报告了药物药代动力学，这些药代动力学与人类遇到的药代动力学相吻合。HFS-TB 研究包括在环境空气中、pH5.8 下的半休眠细菌和低氧张力（≤10 十亿分之一）下的非复制性持久菌的对数期生长研究。这些研究确定了与结核分枝杆菌最佳杀伤和抑制获得性耐药（ADR）相关的抗生素暴露，并对最佳临床剂量、患者标准剂量和方案的预期性能以及 ADR 的预期发生率进行了预测，并提出了新的药敏断点建议。
HFS-TB 模型能够进行包括类似人类的药物暴露在内的 PK/PD 研究，以确定杀菌和杀菌效果率，并确定与抑制耐药相关的暴露。由于能够随着时间的推移从同一单位重复采样，HFS-TB 大大提高了统计能力，并促进了时间事件分析和重复事件分析以及动态系统药理学数学模型的执行。
