Clinical Outcomes with Alternative Dosing Strategies for Piperacillin/Tazobactam: A Systematic Review and Meta-Analysis

Abstract

ObjectivesA better dosing strategy can improve clinical outcomes for patients. We sought to compare the extended or continuous infusion with conventional intermittent infusion of piperacillin/tazobactam, investigating which approach is better and worthy of recommendation for clinical use.MethodsArticles were gathered from PubMed, Web of Science, ProQuest, Science Direct, Cochrane, two Chinese literature databases (CNKI, Wan Fang Data) and related ICAAC and ACCP conferences. Randomized controlled and observational studies that compared extended or continuous infusion with conventional intermittent infusion of piperacillin/tazobactam were identified from the databases above and analyzed. Two reviewers independently extracted and investigated the data. A meta-analysis was performed using Revman 5.2 software. The quality of each study was assessed. Sensitivity analysis and publication bias were evaluated.ResultsFive randomized controlled trials and nine observational studies were included in this study. All included studies had high quality and no publication bias was found. Compared to the conventional intermittent infusion approach, the extended or continuous infusion group had a significantly higher clinical cure rate (OR 1.88, 95% CI 1.29-2.73, P = 0.0009) and a lower mortality rate (OR 0.67, 95% CI 0.50-0.89, P = 0.005). No statistical difference was observed for bacteriologic cure (OR 1.40, 95% CI 0.82-2.37, P = 0.22) between the two dosing regimens. The sensitivity analysis showed the results were stable.ConclusionsOur systematic review and meta-analysis suggested that the extended or continuous infusion strategy of piperacillin/tazobactam should be recommended for clinical use considering its higher clinical cure rate and lower mortality rate in comparison with conventional intermittent strategy. Data from this study could be extrapolated for other β-lactam antimicrobials. Therefore, this dosing strategy could be considered in clinical practice.

Neurotoxic Concentration of Piperacillin during Continuous Infusion in Critically Ill Patients

“…The clinical benefits of the continuous infusion strategy are supported by the results of recent meta-analyses, especially for patients with a high sickness severity and infected by less-susceptible pathogens, such as nonfermenting Gram-negative bacilli (11)(12)(13). In our cohort, the infective organism was not identified for 19 of the 53 patients (35.8%).…”

Continuous and Prolonged Intravenous β-Lactam Dosing: Implications for the Clinical Laboratory

“…Although quite a few of these have been conducted over time, they differ markedly in their inclusion/exclusion criteria, thus not necessarily allowing elucidation of the true effectiveness of nontraditional beta-lactam dosing regimens (4,18,(88)(89)(90)(91)(92)(93)(94)(95)(96)(97)(98)(99)(100)(101)(102). Recent metaanalyses that focused on beta-lactams (Table 3) have mostly concluded that existing data were favorable for the use of specific or all beta-lactam agents by prolonged or continuous infusion in terms of clinical outcomes.…”

Optimizing dosing of antibiotics in critically ill patients

“…However, the evidence for clinical outcome benefit from prolonged infusions of beta-lactam antibiotics is still inconsistently reported, and is yet to be established [34,46]. Meta-analyses of published studies support benefits of reduced length of ICU stay, improved clinical cure rate, [47,48] and/or reduced toxicity [49] with prolonged infusions. However, a recent large multicentre randomized study [45] reported no difference in patient outcomes when comparing continuous versus intermittent infusion of three beta-lactams in 420 patients with severe sepsis.…”