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

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.

• Authors: Christopher Faber, Roel J W Hoogendoorn, Hein P Stallmann, D M Lyaruu, Arie van Nieuw Amerongen, Paul I J M Wuisman, Skeltal Tissue Engineering Group Amsterdam (STEGA)
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 54 Issue 6 Pg. 1078-84 (Dec 2004) ISSN: 0305-7453 [Print] England
• PMID: 15537700 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Gentamicins
• HTN3 protein, human
• Histatins
• Peptides
• Polymethacrylic Acids
• Salivary Proteins and Peptides
• polymethacrylic acid

Topics

• Animals
• Anti-Bacterial Agents (pharmacology)
• Antibiotic Prophylaxis
• Disease Models, Animal
• Femur (microbiology)
• Gentamicins (pharmacology)
• Histatins
• Humans
• Methicillin Resistance
• Microspheres
• Osteomyelitis (microbiology, prevention & control)
• Peptides (chemistry, pharmacology)
• Polymethacrylic Acids (administration & dosage)
• Rabbits
• Salivary Proteins and Peptides (pharmacology)
• Staphylococcal Infections (microbiology, prevention & control)
• Staphylococcus aureus (drug effects)