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JAC Advance Access published online on August 24, 2006
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkl355
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© The Author 2006. 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
Received June 8, 2006
Revised July 14, 2006
Accepted August 8, 2006

Brief report

Comparative activity of cloxacillin and vancomycin against methicillin-susceptible Staphylococcus aureus experimental endocarditis

Manuel L. Fernández Guerrero 1 * and Miguel de Górgolas 1

1 Department of Internal Medicine, Division of Infectious Diseases, Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Spain

* To whom correspondence should be addressed.
Manuel L. Fernández Guerrero, E-mail: mlfernandez{at}fjd.es


  Abstract

Objectives: To compare the activity of cloxacillin and vancomycin against methicillin-susceptible Staphylococcus aureus and to determine how rapidly their bactericidal activity occurs in cardiac vegetations.

Methods: In vitro and in vivo studies using an experimental model of endocarditis in rabbits. Animals were treated for 1, 2 or 3 days with cloxacillin 200 mg/kg intramuscularly three times a day or vancomycin 25 mg/kg intravenously twice a day.

Results: Cloxacillin and vancomycin at concentrations 4- and 16-fold the MIC produced a modest decrease in the number of microorganisms at 4 h. After 24 h, cloxacillin produced a decrease in the counts of staphylococci from 2.19 to 4.84 log10 cfu/mL of inoculum. Only concentrations of vancomycin from 16- to 32-fold the MIC resulted in equivalent decreases. After 24 h of treatment, both antibiotics were equally effective in preventing mortality of rabbits. Cloxacillin produced a greater decrease in the number of staphylococci than vancomycin (3.50 ± 2.18 log10 cfu/g vegetation and 6.25 ± 1.28 log10 cfu/g vegetation, respectively; P < 0.05) and 41% of rabbits had sterile vegetations in comparison with none with vancomycin (P = 0.035). After 48 and 72 h of treatment, both antimicrobials exhibited equivalent activity.

Conclusions: Vancomycin was less rapidly bactericidal than cloxacillin in vivo.

Keywords: {beta}-lactamase-resistant penicillins; glycopeptides; bactericidal activity; staphylococcal bacteraemia.
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