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


CONCLUSIONS
We conclude that both the gentamicin beads and the Dhvar-5 beads were only partially effective at preventing MRSA infection in this model.
Faber
Christopher
C
Department of Orthopaedic Surgery, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands.
Hoogendoorn
Roel J W
RJ
Stallmann
Hein P
HP
Lyaruu
D M
DM
van Nieuw Amerongen
Arie
A
Wuisman
Paul I J M
PI
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D019072:Antibiotic Prophylaxis; D004195:Disease Models, Animal; D005269:Femur / Q000382:microbiology; D005839:Gentamicins / Q000494:pharmacology*; D054808:Histatins; D006801:Humans; D016106:Methicillin Resistance; D008863:Microspheres; D010019:Osteomyelitis / Q000382:microbiology / Q000517:prevention & control*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D011109:Polymethacrylic Acids / Q000008:administration & dosage; D011817:Rabbits; D012471:Salivary Proteins and Peptides / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000382:microbiology / Q000517:prevention & control*; D013211:Staphylococcus aureus / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D005839:Gentamicins; C068075:HTN3 protein, human; D054808:Histatins; D010455:Peptides; D011109:Polymethacrylic Acids; D012471:Salivary Proteins and Peptides; C030613:polymethacrylic acid