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JAC Advance Access originally published online on October 19, 2007
Journal of Antimicrobial Chemotherapy 2007 60(6):1388-1390; doi:10.1093/jac/dkm392
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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

Effect of human plasma on the antimicrobial activity of iclaprim in vitro

H. Laue, T. Valensise, A. Seguin, S. Hawser*, S. Lociuro and K. Islam

Arpida AG, Duggingerstrasse 23, 4153 Reinach, Switzerland

Received 16 August 2007; returned 4 September 2007; revised 14 September 2007; accepted 22 September 2007

* Corresponding author. Tel: +41-61-417-9660; Fax: +41-61-417-9661; E-mail: stephen.hawser{at}arpida.com

Objectives: Iclaprim is a novel diaminopyrimidine for which a human plasma binding level of ~93% has been reported. The purpose of this study was to evaluate the effect of human plasma on the in vitro activity of iclaprim and to compare it with that of fusidic acid, teicoplanin and vancomycin, antibiotics with protein binding to human plasma of 97%, >90% and 55%, respectively.

Methods: MICs were determined using 40 methicillin-susceptible Staphylococcus aureus (MSSA) and 38 methicillin-resistant S. aureus (MRSA) isolates in Mueller–Hinton broth (MHB) alone or in the presence of 50% human plasma.

Results: MICs of iclaprim were not affected by the addition of human plasma. MIC ranges (MIC90) for iclaprim against MSSA and MRSA were ≤0.016–0.06 mg/L (MIC90 0.06 mg/L) and ≤0.016–0.5 mg/L (MIC90 0.06 mg/L), respectively, in MHB and ≤0.016–0.125 mg/L (MIC90 0.06 mg/L) and ≤0.016–0.25 mg/L (MIC90 0.125 mg/L), respectively, in the presence of human plasma. As expected, the antimicrobial activity of fusidic acid was greatly affected by the presence of human plasma (MIC elevations of 4- to >128-fold), whereas MICs of vancomycin remained unchanged. By contrast, despite the high protein binding, MICs of teicoplanin were only marginally affected by the presence of plasma with an MIC elevation of maximum 8-fold for two strains.

Conclusions: This study demonstrates that human plasma does not affect the MIC of iclaprim in vitro.

Keywords: antibiotics , MICs , MRSA , protein binding , Staphylococcus aureus


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