Steady-state pharmacokinetics and pharmacodynamics of piperacillin/tazobactam administered by prolonged infusion in hospitalised patients.

Full Abstract

The objective of this study was to evaluate the steady-state pharmacokinetics and pharmacodynamics of piperacillin/tazobactam, administered by prolonged infusion, in hospitalised patients requiring antimicrobial therapy. Thirteen patients received 4.5 g every 8 h (q8h), infused over 4 h, and pharmacokinetic parameters were determined by non-compartmental methods. Monte Carlo simulations (10,000 patients) were performed to calculate the cumulative fraction of response (CFR) for seven gram-negative pathogens using minimum inhibitory concentration (MIC) data from the Meropenem Yearly Susceptibility Test Information Collection (2004-2007, USA) as well as the probability of target attainment (PTA) at MICs ranging from 1 microg/mL to 64 microg/mL. The pharmacodynamic target was free piperacillin concentration remaining above the MIC for 50% of the dosing interval. Mean+/-standard deviation maximum and minimum serum concentrations, half-life, volume of distribution at steady-state and systemic clearance of piperacillin were 108.2+/-31.7 microg/mL, 27.6+/-26.3 microg/mL, 2.1+/-1.2 h, 22.1+/-4.0 L and 8.6+/-3.0 L/h, respectively. The CFR was > 90% for Escherichia coli, Serratia marcescens and Citrobacter spp., 88.6% for Enterobacter spp., 87% for Klebsiella pneumoniae, 85.5% for Pseudomonas aeruginosa and 52.8% for Acinetobacter spp. The PTA was 100%, 81.1% and 12.3% at MICs of < or = 16 microg/mL, 32 microg/mL and 64 microg/mL, respectively. Piperacillin/tazobactam 4.5 g q8h infused over 4 h provides excellent target attainment for bacterial pathogens with MICs < or = 16 microg/mL. However, the CFR was < 90% for four of the seven gram-negative pathogens evaluated.

Author information

Author/s: Shea, Katherine M (KM); Cheatham, S Christian (SC); Wack, Matthew F (MF); Smith, David W (DW); Sowinski, Kevin M (KM); Kays, Michael B (MB);

Affiliation: Clarian Health Partners, Inc., Methodist Hospital, Department of Pharmacy, Indianapolis, IN, USA.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: International journal of antimicrobial agents (Int J Antimicrob Agents), published in Netherlands. (Language: eng)

Reference: 2009-Nov; vol 34 (issue 5) : pp 429-33

Dates: Created 2009/09/15; Completed 2009/11/06;

PMID: 19726163, status: MEDLINE (last retrieved date: 11/6/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Adult
Aged
Anti-Bacterial Agents - administration & dosage; pharmacokinetics; therapeutic use
Female
Gram-Negative Bacterial Infections - drug therapy
Humans
Infusions, Intravenous
Inpatients

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Anti-Bacterial Agents (0) ; piperacillin-tazobactam combination product (157044-21-8) ; Piperacillin (61477-96-1) ; Penicillanic Acid (87-53-6)

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