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JAC Advance Access published online on November 10, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh441
© 2004 by The British Society for Antimicrobial Chemotherapy
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Received May 14, 2004
Revised August 22, 2004
Accepted August 27, 2004

Original article

In vivo comparison of Dhvar-5 and gentamicin in an MRSA osteomyelitis prevention model

Christopher Faber 1, Roel J. W. Hoogendoorn 2, Hein P. Stallmann 1, D. M. Lyaruu 3, Arie van Nieuw Amerongen 4, Paul I. J. M. Wuisman 2*, and on behalf of STEGA (Skeletal Tissue Engineering Group Amsterdam)

1 Department of Orthopaedic Surgery, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands; Department of Oral Cell Biology, Academic Center for Dentistry Amsterdam (ACTA), The Netherlands
2 Department of Orthopaedic Surgery, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands
3 Department of Oral Cell Biology, Academic Center for Dentistry Amsterdam (ACTA), The Netherlands
4 Department of Oral Biochemistry, ACTA, Universiteit van Amsterdam and Vrije Universiteit, Amsterdam, The Netherlands

* To whom correspondence should be addressed.
Paul I. J. M. Wuisman, E-mail: orthop{at}vumc.nl


  Abstract

Objectives: The continued rise in drug-resistant pathogens has led to global research efforts into new antimicrobial agents. A promising class of new agents are the antimicrobial peptides. The aim of the study was to investigate the efficacy of the antimicrobial peptide Dhvar-5 in a prophylactic, methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis model.

Methods: Dhvar-5 (12 mg or 24 mg/rabbit) was incorporated into polymethyl methacrylate (PMMA) beads as a local drug delivery system. For comparison, plain beads (control) and beads containing gentamicin as a sulphate (10 mg or 24 mg per rabbit) were also prepared. The beads were inserted into the inoculated femoral cavity of 36 rabbits, and 1 week later they were killed. The presence and severity of MRSA osteomyelitis was assessed by culture and histology.

Results: Both the 24 mg Dhvar-5 beads and the 24 mg gentamicin sulphate beads significantly reduced the bacterial load of the inoculated femora compared with the control chain. Although a 24 mg Dhvar-5 dose inhibited MRSA growth, it did not completely sterilize the femora. Sterilization occurred only in some of the gentamicin-treated specimens.

Conclusion: We conclude that both the gentamicin beads and the Dhvar-5 beads were only partially effective at preventing MRSA infection in this model.

Keywords: antimicrobial peptides; drug delivery; rabbits; PMMA beads.
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