整合药代动力学、药效学和 MIC 分布，以评估加拿大医院感染的铜绿假单胞菌临床分离株对抗菌药物活性的变化（CANWARD）。

Integrating pharmacokinetics, pharmacodynamics and MIC distributions to assess changing antimicrobial activity against clinical isolates of Pseudomonas aeruginosa causing infections in Canadian hospitals (CANWARD).

机构信息

Faculty of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada R3E 0T5.

出版信息

J Antimicrob Chemother. 2013 May;68 Suppl 1:i67-72. doi: 10.1093/jac/dkt028.

DOI:10.1093/jac/dkt028

PMID:23587780

Abstract

OBJECTIVES

To study antimicrobial pharmacodynamic (PD) activity over time against clinical isolates of Pseudomonas aeruginosa in Canadian hospitals.

METHODS

Integrated pharmacokinetic (PK)/PD analyses with Monte Carlo simulations were used to study cefepime, meropenem, piperacillin/tazobactam, ciprofloxacin, amikacin, gentamicin and colistin. Profiles of P. aeruginosa infections were modelled using CANWARD data from January 2007 to June 2012 inclusive. The probability of target attainment (PTA) was the proportion of cases achieving a %ƒT>MIC ≥ 50% for cefepime, meropenem and piperacillin/tazobactam, an ƒAUC/MIC ≥ 90 for ciprofloxacin and the aminoglycosides, and a total AUC/MIC ≥ 60 for colistin.

RESULTS

Some 2126 P. aeruginosa isolates were identified. There were no significant trends over time in the PTA for cefepime (0.93-1.0), meropenem (0.89-0.92) or piperacillin/tazobactam (0.74-0.79) (data shown for the highest recommended doses). The PD activity for ciprofloxacin (PTA 0.48-0.64) was variable. There were notable improvements in the PTA for amikacin (from 0.21 to 0.55, P = 0.027), gentamicin (from 0.10 to 0.51, P = 0.035) and colistin (from 0.04 to ~0.20, P = 0.05), which were not reliably detected by MIC indices. There was a decline over time in the PTA for piperacillin/tazobactam from 0.73 to 0.61 against P. aeruginosa isolated from intensive care units (ICUs) (Pearson correlation coefficient -0.99, P = 0.003). Neither MIC50 nor MIC90 detected this reduction in PD activity.

CONCLUSIONS

The overall PD activity against P. aeruginosa was stable from 2007 to 2012 for cefepime, meropenem and piperacillin/tazobactam, was variable and unreliable for ciprofloxacin, and improved significantly but remained relatively low for the aminoglycosides and colistin. There was a progressive reduction over time in the PD activity of piperacillin/tazobactam against ICU isolates, which was not detected by simply assessing MIC indices.

摘要

目的

研究加拿大医院临床分离铜绿假单胞菌的抗菌药物药代动力学（PK）/药效学（PD）随时间的变化。

方法

使用蒙特卡罗模拟对头孢吡肟、美罗培南、哌拉西林/他唑巴坦、环丙沙星、阿米卡星、庆大霉素和多粘菌素的药代动力学（PK）/药效学（PD）进行综合分析。使用 2007 年 1 月至 2012 年 6 月期间的加拿大国家监测数据（CANWARD），建立铜绿假单胞菌感染模型。目标浓度时间曲线下面积（AUC）/MIC 比值≥60 为多粘菌素的达标概率（PTA），头孢吡肟、美罗培南和哌拉西林/他唑巴坦的 PTA 为 %ƒT>MIC≥50%，环丙沙星和氨基糖苷类的 PTA 为ƒAUC/MIC≥90%。

结果

共鉴定出 2126 株铜绿假单胞菌。在研究期间，头孢吡肟（0.93-1.0）、美罗培南（0.89-0.92）或哌拉西林/他唑巴坦（0.74-0.79）的 PTA 没有显著变化（数据显示为最高推荐剂量）。环丙沙星的 PD 活性（PTA 0.48-0.64）差异较大。阿米卡星（从 0.21 升至 0.55，P=0.027）、庆大霉素（从 0.10 升至 0.51，P=0.035）和多粘菌素（从 0.04 升至 0.20，P=0.05）的 PTA 显著改善，而 MIC 指数无法可靠地检测到这些变化。哌拉西林/他唑巴坦对重症监护病房（ICU）分离的铜绿假单胞菌的 PTA 从 0.73 降至 0.61（Pearson 相关系数-0.99，P=0.003）。MIC50 和 MIC90 均无法检测到这种 PD 活性的降低。

结论

2007 年至 2012 年期间，头孢吡肟、美罗培南和哌拉西林/他唑巴坦对铜绿假单胞菌的总体 PD 活性稳定，环丙沙星的 PD 活性不稳定且不可靠，氨基糖苷类和多粘菌素的 PD 活性显著改善，但仍相对较低。哌拉西林/他唑巴坦对 ICU 分离株的 PD 活性随时间逐渐降低，而 MIC 指数检测不到这种变化。