Population Pharmacokinetics of Piperacillin in Non-Critically Ill Patients with Bacteremia Caused by Enterobacteriaceae

Merino-Bohorquez, Vicente, Docobo-Perez, Fernando, Valiente-Mendez, Adoracion, Delgado-Valverde, Mercedes, Camean, Manuel, Hope, William W ORCID: 0000-0001-6187-878X, Pascual, Alvaro and Rodriguez-Bano, Jesus (2021) Population Pharmacokinetics of Piperacillin in Non-Critically Ill Patients with Bacteremia Caused by Enterobacteriaceae. ANTIBIOTICS-BASEL, 10 (4). 348-.

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Abstract

This study analyzes the pharmacokinetic variability of piperacillin in non-critically ill patients with Enterobacteriaceae bloodstream infections (EBSI) and explores predicted clinical outcomes and piperacillin-related neurotoxicity under different renal conditions. Hospitalized, non-critically ill patients treated with piperacillin-tazobactam for EBSI were included. Four serum samples per patient were collected and analyzed. A population pharmacokinetic model was developed using the Pmetrics package for R. Monte Carlo simulations of various dosage regimens of 4 g piperacillin, administered q8 h or q12 h by short (0.5 h) or long (4 h) infusion, following the different glomerular filtration rate (GFR) categories used to classify chronic kidney disease (Kidney Disease: Improving Global Outcomes, KDIGO) to determine the probability of target attainment (PTA) using a free drug concentrations above the minimal inhibitory concentration (<i>f</i>T > MIC) of 50% for efficacy and targets for piperacillin-associated neurotoxicity. Twenty-seven patients (102 samples) were included. Extended piperacillin infusions reached a PTA > 90% (50%<i>f</i>T > MIC) within the susceptibility range, although a loading dose did not greatly improve the expected outcome. Long infusions reduced the expected toxicity in patients with severe renal impairment. The study supports the use of extended infusions of piperacillin in non-critically ill patients with EBSI. No benefits of a loading dose were expected in our population. Finally, extended infusions may reduce the risk of toxicity in patients with severe renal impairment.

Item Type:	Article
Uncontrolled Keywords:	bloodstream infection, renal function, neurotoxicity, nephrotoxicity, pharmacokinetics, piperacillin&#8211, tazobactam, Enterobacteriaceae
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	07 Jul 2021 10:23
Last Modified:	09 Feb 2024 01:43
DOI:	10.3390/antibiotics10040348
Open Access URL:	https://doi.org/10.3390/antibiotics10040348
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3129132