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Critical Care
Published in: Critical Care 4/2010

Open Access 01-08-2010 | Research

Insufficient β-lactam concentrations in the early phase of severe sepsis and septic shock

Authors: Fabio Silvio Taccone, Pierre-François Laterre, Thierry Dugernier, Herbert Spapen, Isabelle Delattre, Xavier Wittebole, Daniel De Backer, Brice Layeux, Pierre Wallemacq, Jean-Louis Vincent, Frédérique Jacobs

Published in: Critical Care | Issue 4/2010

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Abstract

Introduction

Altered pharmacokinetics (PK) in critically ill patients can result in insufficient serum β-lactam concentrations when standard dosages are administered. Previous studies on β-lactam PK have generally excluded the most severely ill patients, or were conducted during the steady-state period of treatment. The aim of our study was to determine whether the first dose of piperacillin-tazobactam, ceftazidime, cefepime, and meropenem would result in adequate serum drug concentrations in patients with severe sepsis and septic shock.

Methods

Open, prospective, multicenter study in four Belgian intensive care units. All consecutive patients with a diagnosis of severe sepsis or septic shock, in whom treatment with the study drugs was indicated, were included. Serum concentrations of the antibiotics were determined by high-pressure liquid chromatography (HPLC) before and 1, 1.5, 4.5 and 6 or 8 hours after administration.

Results

80 patients were treated with piperacillin-tazobactam (n = 27), ceftazidime (n = 18), cefepime (n = 19) or meropenem (n = 16). Serum concentrations remained above 4 times the minimal inhibitory concentration (T > 4 × MIC), corresponding to the clinical breakpoint for Pseudomonas aeruginosa defined by the European Committee on Antimicrobial Susceptibility Testing (EUCAST), for 57% of the dosage interval for meropenem (target MIC = 8 μg/mL), 45% for ceftazidime (MIC = 32 μg/mL), 34% for cefepime (MIC = 32 μg/mL), and 33% for piperacillin-tazobactam (MIC = 64 μg/mL). The number of patients who attained the target PK profile was 12/16 for meropenem (75%), 5/18 for ceftazidime (28%), 3/19 (16%) for cefepime, and 12/27 (44%) for piperacillin-tazobactam.

Conclusions

Serum concentrations of the antibiotic after the first dose were acceptable only for meropenem. Standard dosage regimens for piperacillin-tazobactam, ceftazidime and cefepime may, therefore, be insufficient to empirically cover less susceptible pathogens in the early phase of severe sepsis and septic shock.
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Metadata
Title
Insufficient β-lactam concentrations in the early phase of severe sepsis and septic shock
Authors
Fabio Silvio Taccone
Pierre-François Laterre
Thierry Dugernier
Herbert Spapen
Isabelle Delattre
Xavier Wittebole
Daniel De Backer
Brice Layeux
Pierre Wallemacq
Jean-Louis Vincent
Frédérique Jacobs
Publication date
01-08-2010
Publisher
BioMed Central
Published in
Critical Care / Issue 4/2010
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc9091

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