Population Health Sciences, Bristol Medical School, University of Bristol, Canynge Hall, Bristol BS8 2PS, UK.
Institute of Clinical Pharmacodynamics, 242 Broadway, Schenectady, New York 12305, USA.
J Antimicrob Chemother. 2020 Jun 1;75(6):1374-1389. doi: 10.1093/jac/dkaa005.
Pharmacokinetic (PK)-pharmacodynamic (PD) indices relate measures of drug exposure to antibacterial effect. Clinical PK-PD studies aim to correlate PK-PD indices with outcomes in patients. Optimization of dosing based on pre-clinical studies means that PK-PD relationships are difficult to establish; therefore studies need to be designed and reported carefully to validate pre-clinical findings.
To describe the methodological features of clinical antibacterial and antifungal PK-PD studies that reported the relationship between PK-PD indices and clinical or microbiological responses.
Studies published between 1980 and 2015 were identified through systematic searches. Methodological features of eligible studies were extracted.
We identified 85 publications containing 97 PK-PD analyses. Most studies were small, with fewer than 100 patients. Around a quarter were performed on patients with infections due to a single specific pathogen. In approximately one-third of studies, patients received concurrent antibiotics/antifungals and in some other studies patients received other treatments that may confound the PK-PD-outcome relationship. Most studies measured antimicrobial concentrations in blood/serum and only four measured free concentrations. Most performed some form of regression, time-to-event analysis or used the Hill/Emax equation to examine the association between PK-PD index and outcome. Target values of PK-PD indices that predict outcomes were investigated in 52% of studies. Target identification was most commonly done using recursive partitioning or logistic regression.
Given the variability in conduct and reporting, we suggest that an agreed set of standards for the conduct and reporting of studies should be developed.
药代动力学（PK）-药效动力学（PD）指标将药物暴露与抗菌作用相关联。临床 PK-PD 研究旨在将 PK-PD 指标与患者的结果相关联。基于临床前研究进行剂量优化意味着 PK-PD 关系难以建立；因此，需要仔细设计和报告研究以验证临床前发现。
描述报告 PK-PD 指标与临床或微生物学反应之间关系的临床抗菌和抗真菌 PK-PD 研究的方法学特征。
通过系统搜索确定了 1980 年至 2015 年期间发表的研究。提取合格研究的方法学特征。
我们确定了 85 篇包含 97 项 PK-PD 分析的出版物。大多数研究规模较小，患者少于 100 例。大约四分之一的研究是针对单一特定病原体引起的感染患者进行的。在大约三分之一的研究中，患者同时接受抗生素/抗真菌药物治疗，而在其他一些研究中，患者接受其他可能干扰 PK-PD-结果关系的治疗。大多数研究测量血液/血清中的抗菌浓度，只有四项研究测量游离浓度。大多数研究采用某种形式的回归、时间事件分析或使用 Hill/Emax 方程来检查 PK-PD 指数与结果之间的关联。52%的研究调查了预测结果的 PK-PD 指数的目标值。目标识别最常使用递归分区或逻辑回归进行。
鉴于研究的实施和报告存在差异，我们建议应制定一套用于研究实施和报告的商定标准。
