Prolonged vs intermittent infusion of piperacillin/tazobactam in critically ill patients: a narrative and systematic review.

The purpose of this study is to review the rationale of prolonged (ie, extended or continuous) infusion of piperacillin/tazobactam (PIP/TAZ) in critically ill patients and to perform a systematic review that compare the effectiveness of prolonged infusion with intermittent bolus of PIP/TAZ. A search of Medline, Web of Science, Embase, and Cochrane databases was conducted up to April 2014. For systematic review, studies comparing the effectiveness of prolonged and bolus administration of PIP/TAZ were included. The level of evidence is determined using best-evidence synthesis, which consisted of 5 possible levels of evidence: strong, moderate, limited, conflicting, or no evidence. The pharmacokinetic/pharmacodynamic studies that account for an eventual benefit of prolonged PIP/TAZ infusion were reviewed. In the systematic review, 1 randomized controlled trial was identified that showed higher "cure" in the prolonged than in the intermittent infusion group, yet the chosen clinical outcome in this study, decline in mean Acute Physiology and Chronic Health Evaluation II score is controversial. Of 6 retrospective cohort studies, 4 showed either less mortality, a higher clinical cure rate, or shorter length of hospital stay with prolonged PIP/TAZ treatment. The level of evidence supporting a better clinical outcome with prolonged infusion of PIP/TAZ is moderate. Pharmacokinetic/pharmacodynamic studies provide a robust rationale to prefer prolonged above intermittent infusion of PIP/TAZ. However, although some studies suggest a better outcome in critically ill patients receiving prolonged infusion, the level of evidence is moderate.