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Clinical Outcomes of Extended Versus Intermittent Infusion of Piperacillin-Tazobactam in Critically Ill Patients: a Prospective Clinical Trial
Fan S, Shum H, Cheng W, et al. Pharmacotherapy. 2017;37:109-119.
Study Question: Does extended-infusion (EI) administration of piperacillin-tazobactam improve clinical outcomes compared to patients receiving intermittent infusions (NEI)?
Study Description: This was a single-center, open-label, randomized, prospective study. Adult patients admitted to a mixed medical-surgical intensive care unit diagnosed with either bacterial infection or neutropenic fever were included in the study. Patients were randomized to either EI (4.5 g every 8-12 hours over 4 hours) or NEI (4.5 g every 6-8 hours over 30 minutes). Both groups received dose adjustments based on renal function.
Results: A total of 367 patients were included in the study. Baseline demographics differed slightly between the groups with more patients on immunosuppressants in the EI group and significantly fewer patients with diabetes in the EI group. No statistically significant difference was found in 14-day mortality between the EI and NEI groups (11.5% vs. 15.7%, p = 0.29). Secondarily, the mean time to defervescence, defined as the first day when oral, tympanic, or axillary temperature was < 38.0°C or when rectal or core temperature was < 38.5°C for the entire 24 hours, was significantly reduced by 2 days in the EI group compared to the NEI group (4 days vs. 6 days, p = 0.01). A post-hoc analysis suggested the impact of EI piperacillin-tazobactam on 14-day mortality was most favorable in those patients with positive cultures and those with respiratory tract infections.
Conclusion(s): Administration of EI piperacillin-tazobactam in critically ill patients did not improve 14-day mortality as compared to NEI piperacillin-tazobactam.
Perspective: This study directly contradicts previously published data regarding the impact of EI piperacillin-tazobactam. Extended-infusion piperacillin-tazobactam has been shown in retrospective and observational studies to improve mortality, which is supported by systematic reviews and meta-analyses. Without additional data, this study does not negate the impact of the previously published data, and it is still appropriate to continue to use EI piperacillin-tazobactam as an empiric treatment in critically ill patients.