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JAC Advance Access originally published online on November 10, 2004
Journal of Antimicrobial Chemotherapy 2004 54(6):1078-1084; doi:10.1093/jac/dkh441
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JAC vol.54 no.6 © The British Society for Antimicrobial Chemotherapy 2004; all rights reserved

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

Christopher Faber1,2, Roel J. W. Hoogendoorn1, Hein P. Stallmann1,2, D. M. Lyaruu2, Arie van Nieuw Amerongen3 and Paul I. J. M. Wuisman1,* on behalf of STEGA (Skeletal Tissue Engineering Group Amsterdam)

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

* Corresponding author. Tel: +31-20-4442355; Fax: +31-20-4442357; Email: orthop{at}vumc.nl

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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