Mar 29, 2020

Brain Exposure to Piperacillin in Acute Hemorrhagic Stroke Patients Assessed by Cerebral Microdialysis and Population Pharmacokinetics

Neurocritical Care
Sami UllahRaimund Helbok

Abstract

The broad antibacterial spectrum of piperacillin/tazobactam makes the combination suitable for the treatment of nosocomial bacterial central nervous system (CNS) infections. As limited data are available regarding piperacillin CNS exposure in patients without or with low-grade inflammation, a clinical study was conducted (1) to quantify CNS exposure of piperacillin by cerebral microdialysis and (2) to evaluate different dosing regimens in order to improve probability of target attainment (PTA) in brain. Ten acute hemorrhagic stroke patients (subarachnoid hemorrhage, n = 6; intracerebral hemorrhage, n = 4) undergoing multimodality neuromonitoring received 4 g piperacillin/0.5 g tazobactam every 8 h by 30-min infusions for the management of healthcare-associated pneumonia. Cerebral microdialysis was performed as part of the clinical neuromonitoring routine, and brain interstitial fluid samples were retrospectively analyzed for piperacillin concentrations after the first and after multiple doses for at least 5 days and quantified by high-performance liquid chromatography. Population pharmacokinetic modeling and Monte Carlo simulations with various doses and types of infusions were performed to predict exposure. A T>MIC of 50% was ...Continue Reading

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Mentioned in this Paper

Retrospective Studies
Brain
Piperacillin
Pharmacokinetic Study
Central Nervous System
Plasma
Pharmacodynamics
Minimum Inhibitory Concentration Result
Meningitis
Subarachnoid Hemorrhage

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