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JAC Advance Access originally published online on January 23, 2009
Journal of Antimicrobial Chemotherapy 2009 63(3):564-567; doi:10.1093/jac/dkn522
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© The Author 2009. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Original research

Plasma and peritoneal concentration following continuous infusion of cefotaxime in patients with secondary peritonitis

Philippe Seguin1,*, Marie Clémence Verdier2, Charles Chanavaz1, Charlotte Engrand1, Bruno Laviolle2, Pierre-Yves Donnio3 and Yannick Mallédant1

1 Service de Réanimation Chirurgicale—Inserm U620, Université Rennes 1, Hôpital de Pontchaillou, 2 Rue Henri le Guilloux, 35033 Rennes Cedex 9, Rennes, France 2 Service de Pharmacologie et Centre d'Investigation Clinique—Inserm 0203, Université Rennes 1, Hôpital de Pontchaillou, 2 Rue Henri le Guilloux, 35033 Rennes Cedex 9, Rennes, France 3 Laboratoire de Bactériologie–Virologie, Université Rennes 1, Hôpital de Pontchaillou, 2 Rue Henri le Guilloux, 35033 Rennes Cedex 9, Rennes, France

Received 18 June 2008; returned 9 September 2008; revised 21 November 2008; accepted 7 December 2008

* Corresponding author. Tel: +33-2-99-28-42-46; Fax: +33-2-99-28-24-21; E-mail: philippe.seguin{at}chu-rennes.fr

Objectives: The aim of this study was to determine the steady-state plasma and peritoneal concentrations of cefotaxime and its metabolite desacetyl-cefotaxime administered by continuous infusion to critically ill patients with secondary peritonitis.

Patients and methods: In 11 patients, a continuous infusion of 4 g/24 h of cefotaxime following a bolus of 2 g was evaluated. Plasma and peritoneal levels of cefotaxime and desacetyl-cefotaxime were measured at steady state on days 2 and 3 (plasma) and on day 3 (peritoneal) by HPLC. Results are expressed as means ± SD.

Results: Total and unbound plasma levels of cefotaxime were 24.0 ± 21.5 and 20.3 ± 19.8 mg/L on day 2 and 22.1 ± 20.7 and 18.9 ± 19.2 mg/L on day 3, respectively. Total and unbound levels of cefotaxime in the peritoneal fluids were 16.2 ± 11.5 and 14.3 ± 10.4 mg/L, respectively. The unbound fraction of plasma cefotaxime was 81.8 ± 5.9% on day 2 and 82.6 ± 7.7% on day 3, and the unbound fraction at the peritoneal site was 87.0 ± 5.5% on day 3. Total and unbound plasma levels of desacetyl-cefotaxime were 9.0 ± 8.1 and 8.4 ± 8.1 mg/L on day 2 and 7.6 ± 7.6 and 7.2 ± 7.6 mg/L on day 3, respectively. Total and unbound levels of desacetyl-cefotaxime in the peritoneal fluids were 11.9 ± 11.5 and 10.9 ± 10.8 mg/L, respectively. The MICs for the enterobacteria recovered ranged from 0.016 to 0.25 mg/L.

Conclusions: Continuous infusion of 4 g/24 h of cefotaxime provided a peritoneal concentration >5x MIC for the recovered Enterobacteriaceae and the susceptibility breakpoint of cefotaxime for facultative Gram-negative bacilli.

Keywords: human , critically ill patients , high performance liquid chromatography , protein binding


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