Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Ann Pharmacother. 2012 Feb;46(2):265-75. doi: 10.1345/aph.1Q378. Epub 2012 Jan 24.
To perform a qualitative systematic review of the evidence comparing traditional strategies against prolonged intermittent or continuous infusion strategies for piperacillin/tazobactam, based on clinical and pharmacodynamic outcomes.
MEDLINE (1950-September 2011), EMBASE (1980-September 2011), and International Pharmaceutical Abstracts (1970-September 2011) were searched, using the terms piperacillin, tazobactam, pharmacokinetics, pharmacodynamics, dosing, and infusion. Reference lists from relevant publications were also reviewed.
Articles evaluating the administration of piperacillin/tazobactam to adults and comparing at least 2 dosing regimens (1 of which included the traditional, manufacturer-recommended 30-minute infusion; the other, a prolonged or continuous infusion strategy) were included. Prespecified clinical outcomes of interest included mortality, clinical cures, and adverse events. The pharmacodynamic endpoint of interest was percent time of unbound drug concentration remaining above the minimum inhibitory concentration.
Twelve studies were included in this review, 7 of which assessed clinical outcomes and 5 that assessed pharmacodynamic endpoints using Monte Carlo simulations. Prolonged or continuous infusions of piperacillin/tazobactam consistently achieved higher pharmacodynamic endpoints than did traditional infusions. The association of prolonged or continuous infusions with improved clinical outcomes, however, is unclear. Two retrospective studies found improved mortality rates with prolonged infusions (1 in a subgroup of patients with higher APACHE II [Acute Physiology and Chronic Health Evaluation II] scores), while another retrospective study found improved clinical cure rates with continuous infusions in patients with ventilator-associated pneumonia. These clinical benefits have not been substantiated in prospective randomized trials. No study has provided evidence of reduced adverse effects with prolonged or continuous infusions.
The limited evidence available does not firmly support widespread adoption of administering piperacillin/tazobactam as prolonged intermittent or continuous infusions to improve clinical outcomes despite the achievement of higher pharmacodynamic targets in simulated studies. Retrospective studies indicate that critical care patients are the subgroup most likely to benefit from these dosing strategies. Well-designed prospective clinical trials are required to confirm potential benefits observed in retrospective studies.
对比较哌拉西林/他唑巴坦传统策略与延长间歇性或连续性输注策略的基于临床和药效动力学结果的证据进行定性系统评价。
检索 MEDLINE（1950 年-2011 年 9 月）、EMBASE（1980 年-2011 年 9 月）和国际药学文摘（1970 年-2011 年 9 月），使用哌拉西林、他唑巴坦、药代动力学、药效动力学、给药和输注等术语。还查阅了相关出版物的参考文献列表。
纳入评估哌拉西林/他唑巴坦在成人中的给药并比较至少 2 种给药方案（其中 1 种包括传统的、制造商推荐的 30 分钟输注；另一种为延长或连续输注策略）的文章。感兴趣的预设临床结局包括死亡率、临床治愈率和不良事件。关注的药效动力学终点为未结合药物浓度超过最低抑菌浓度的时间百分比。
本综述纳入了 12 项研究，其中 7 项评估临床结局，5 项使用蒙特卡罗模拟评估药效动力学终点。与传统输注相比，延长或连续输注哌拉西林/他唑巴坦始终能达到更高的药效动力学终点。然而，延长或连续输注与改善临床结局的相关性尚不清楚。两项回顾性研究发现延长输注可降低死亡率（1 项在更高的急性生理学和慢性健康评估 II [APACHE II]评分的亚组患者中），而另一项回顾性研究发现连续输注在呼吸机相关性肺炎患者中可提高临床治愈率。这些临床益处尚未在前瞻性随机试验中得到证实。没有研究提供证据表明延长或连续输注可减少不良反应。
现有有限的证据不能有力支持广泛采用延长间歇性或连续性输注来改善临床结局，尽管模拟研究显示达到了更高的药效动力学目标。回顾性研究表明，重症监护患者是最有可能从这些给药策略中获益的亚组。需要进行精心设计的前瞻性临床试验来证实回顾性研究中观察到的潜在益处。
