Prolonged Versus Intermittent Piperacillin-Tazobactam Infusion in Critically Ill Patients: A Systematic Review and Meta-Analysis of Randomized Trials.

Authors

Kana Satake, Kenta Iijima

Published in

Chemotherapy. Nov 06, 2026. Epub Nov 06, 2026.

Abstract

Prolonged infusion of β-lactam antibiotics is recommended for adults with sepsis, but whether this benefit applies specifically to piperacillin-tazobactam remains uncertain. We conducted a systematic review and meta-analysis of randomized controlled trials comparing prolonged with intermittent infusion of piperacillin-tazobactam in critically ill adults.
We searched PubMed, Scopus, and the Cochrane Central Register of Controlled Trials from inception to March 10, 2026. Eligible randomized controlled trials compared prolonged (continuous or extended) with intermittent infusion of piperacillin-tazobactam in critically ill adults. Primary outcomes were clinical cure and all-cause mortality. Secondary outcomes included intensive care unit length of stay and duration of antibiotic therapy. Random-effects meta-analyses were performed to calculate pooled risk ratios for dichotomous outcomes and mean differences for continuous outcomes.
Seven studies comprising 6,080 patients were included. For clinical cure, the pooled estimate favored prolonged infusion (risk ratio 1.23, 95% confidence interval 1.07-1.42, 6 trials, 585 participants; very low-certainty evidence). The effect on 28-day mortality was uncertain (risk ratio 0.47, 95% confidence interval 0.16-1.41, 2 trials, 104 participants; low-certainty evidence). There was no clear difference in 90-day mortality (risk ratio 0.92, 95% confidence interval 0.84-1.01, 2 trials, 5,532 participants; moderate-certainty evidence). BLING III contributed 99.3% of the weight in the analysis. The pooled mean difference in antibiotic treatment duration was -2.47 days (95% confidence interval -3.92 to -1.02, 2 trials, 120 participants; very low-certainty evidence), but the evidence was very uncertain.
In this meta-analysis of randomized controlled trials, prolonged infusion of piperacillin-tazobactam may improve clinical cure in critically ill adults, but the evidence is very uncertain. The estimate for 90-day mortality was consistent with the direction of benefit reported for β-lactams overall, but the confidence interval included no effect. These findings are consistent with the class-level evidence but do not independently confirm a mortality benefit specific to piperacillin-tazobactam. The effects on 28-day mortality and antibiotic treatment duration remain uncertain.

PMID:
42993165
Bibliographic data and abstract were imported from PubMed on 06 Nov 2026.

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