Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Pharmacotherapy. 2013 Oct;33(10):1022-34. doi: 10.1002/phar.1310. Epub 2013 Jun 6.
To use pharmacokinetic/pharmacodynamic (PK/PD) modeling to correlate predicted antibiotic efficacy with actual clinical outcomes in patients with serious infections.
Retrospective cohort analysis.
University medical center.
A total of 182 adult intensive care patients with Pseudomonas aeruginosa pneumonia during a 5-year period from 2000 to 2004.
The primary study end point was correlation of predicted antibiotic efficacy as determined by PK/PD modeling with actual clinical outcomes in individual patients. PK/PD analyses were conducted by determination of PD indexes using calculated patient-specific PK parameters and known pathogen minimum inhibitory concentrations, and by determination of predicted PD target attainment by using Monte Carlo simulation. Patients achieving PD targets were predicted to have clinically responded to therapy; patients not achieving PD targets were predicted to have failed therapy. A total of 128 patients (70%) apparently achieved desired PD targets; however, PK/PD modeling correctly predicted actual clinical outcome in only 47% of patients (86 of 182) with sensitivity of 49% and specificity of 43%. Percentages of patients apparently achieving PD targets were similar among those experiencing clinical response or clinical failure (67% vs 74%, respectively; p=0.344). Predicted achievement of PD targets was significantly associated only with reduction in intensive care unit and hospital lengths of stay. Achievement of PD targets was not significantly associated with clinical response by univariate or multivariate analysis, but factors related to severity of illness were significantly associated with clinical response.
PK/PD modeling did not accurately predict clinical or microbiologic success in patients with P. aeruginosa pneumonia. This study highlights the difficulties in applying PK/PD modeling at the level of the individual patient due to extreme PK variability and issues such as severity of illness. Antibiotic dosing based on sound PK/PD principles is strongly advocated, but additional studies are needed to confirm the role of PK/PD modeling in optimizing outcomes of patients with serious bacterial infections.
运用药代动力学/药效学（PK/PD）模型，将预测的抗生素疗效与严重感染患者的实际临床结局相关联。
回顾性队列分析。
大学医学中心。
2000 年至 2004 年 5 年间共 182 例成人重症监护病房铜绿假单胞菌肺炎患者。
主要研究终点是通过 PK/PD 模型确定的预测抗生素疗效与个体患者的实际临床结局的相关性。通过确定患者特定的 PK 参数和已知病原体最小抑菌浓度的 PD 指标进行 PK/PD 分析，并通过使用蒙特卡罗模拟确定预测的 PD 目标达标情况进行 PD 目标预测。达到 PD 目标的患者预计对治疗有临床反应；未达到 PD 目标的患者预计治疗失败。共有 128 例患者（70%）明显达到了所需的 PD 目标；然而，PK/PD 模型仅正确预测了 182 例患者中的 47%（86 例）的实际临床结局，其敏感性为 49%，特异性为 43%。在经历临床反应或临床失败的患者中，达到 PD 目标的患者比例相似（分别为 67%和 74%；p=0.344）。PD 目标的预测达成仅与重症监护病房和住院时间的缩短显著相关。单因素和多因素分析均未显示 PD 目标的达成与临床反应显著相关，但与疾病严重程度相关的因素与临床反应显著相关。
PK/PD 模型不能准确预测铜绿假单胞菌肺炎患者的临床或微生物学疗效。本研究强调了由于 PK 变异性和疾病严重程度等问题，在个体患者层面应用 PK/PD 模型存在困难。强烈主张基于合理 PK/PD 原则进行抗生素剂量给药，但需要进一步研究来确认 PK/PD 模型在优化严重细菌感染患者结局中的作用。
