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JAC Advance Access originally published online on June 13, 2007
Journal of Antimicrobial Chemotherapy 2007 60(2):328-333; doi:10.1093/jac/dkm190
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© The Author 2007. 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

Propensity to release endotoxin after two repeated doses of cefuroxime in an in vitro kinetic model: higher release after the second dose

G. Goscinski1,*, E. Tano2, E. Löwdin1 and J. Sjölin1

1 Section of Infectious Diseases, Department of Medical Sciences, Uppsala University, Uppsala, Sweden 2 Section of Clinical Microbiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden

Received 28 December 2006; returned 28 January 2007; revised 27 March 2007; accepted 8 May 2007

* Corresponding author. Tel: +46-18-6115663; Fax: +46-18-6115650; E-mail: gunilla.hjerdt.goscinski{at}akademiska.se

Objectives: To study endotoxin release from two strains of Escherichia coli after exposure to two repeated doses of cefuroxime in an in vitro kinetic model.

Methods: Cefuroxime in concentrations simulating human pharmacokinetics was added to the bacterial solution with a repeated dose after 12 h. In another experiment, tobramycin was given concomitantly with the second dose of cefuroxime. Samples for viable counts and endotoxin analyses were drawn before the addition of antibiotics and at 2 and 4 h after each dose.

Results: The propensity to release endotoxin, expressed as log10 endotoxin release (EU)/log10 killed bacteria, was higher after the second than after the first dose, 0.80 ± 0.04 and 0.65 ± 0.01, respectively, in the ATCC strain and 0.80 ± 0.04 and 0.65 ± 0.02, respectively, in the clinical strain (P < 0.001). Endotoxin was released earlier after the second dose (P < 0.001). Addition of tobramycin at the second dose reduced the endotoxin release in comparison with that of cefuroxime alone (P < 0.001).

Conclusions: The propensity to liberate endotoxin is higher after the second dose of cefuroxime than after the first, resulting in a higher release of endotoxin than expected from bacterial count. The release after the second dose can be reduced by the addition of tobramycin.

Keywords: aminoglycosides , Escherichia coli , morphology


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