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01.08.2010 | Research | Ausgabe 4/2010 Open Access

Critical Care 4/2010

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

Zeitschrift:
Critical Care > Ausgabe 4/2010
Autoren:
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
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​cc9091) contains supplementary material, which is available to authorized users.

Competing interests

FST, FJ, JLV, TD and PFL have received honoraria for lectures from Astra Zeneca. JLV is also on the speakers list of GlaxoSmithKline. The other authors declare that they have no competing interests.

Authors' contributions

FJ and PFL conceived the study protocol. FST, FJ, PFL, TD, XW, BL and HS participated in the design and coordination of the study. ID and PW performed the PK analyses. FST, PFL, DDB, JLV and FJ drafted the present manuscript. All authors read and approved the final manuscript.

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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