JAC Advance Access published online on April 25, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg258
© 2003 by The British Society for Antimicrobial Chemotherapy
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Original article
1 Department of Orthopaedic
Surgery, Vrije Universiteit Medical Center (VUMC), Amsterdam; Department
of Oral Cell Biology, Academic Centre
for Dentistry Amsterdam (ACTA), Vrije Universiteit, Amsterdam, The
Netherlands
* Corresponding author. E-mail: c.faber.ocb.acta{at}med.vu.nl.
Received 5 November 2002
; revised 6 December 2002
; accepted 18 March 2003
Osteomyelitis is still a major cause of morbidity and
remains a difficult complication to treat in orthopaedic surgery.
The treatment of choice is a combination of systemic and local antibiotics. The
insertion of gentamicin-loaded polymethylmethacrylate (PMMA) beads
into the bone results in high local concentrations of gentamicin
and low systemic concentrations. However, the effectiveness of
this treatment is being hampered by the emergence of antimicrobial
resistance. New antimicrobial agents are therefore needed. One new
class of promising antibiotics is antimicrobial peptides (AMP).
Derived from natural human peptides, these have a low tendency to induce
antimicrobial resistance. Dhvar-5 is an antimicrobial peptide based
on histatin-5, which is found in human saliva and consists of 14
amino acids. It has demonstrated bactericidal activity in
vitro. In order to develop a new local treatment using Dhvar-5
for osteomyelitis, we investigated its release from PMMA beads and
its antimicrobial activity against a clinical isolate of methicillin-resistant Staphylococcus aureus (MRSA) before and after release
from PMMA beads. Specific amounts of Dhvar-5 were incorporated into
PMMA mini beads, containing 120, 600 and 1200 µg
of Dhvar-5, respectively. Dhvar-5 was released from the beads in
all three groups. Total release from the 120 µg
beads was 9 µg per bead after 7 days.
However, the release per bead in the 600 and 1200 µg
beads was far more, respectively, 416 and 1091 µg
over a 28 day period. After release, the Dhvar-5 also retained its
antimicrobial activity against MRSA. On the basis of these data
we conclude that the amount of Dhvar-5 release from PMMA beads is
not proportionate to the amount incorporated; instead, it demonstrated
an exponential relationship to the amount of total peptide released.
Furthermore, the released peptide remained biologically active against
a clinical isolate of MRSA.
Keywords: antimicrobial peptides, Dhvar-5, PMMA beads,
release kinetics
Release of antimicrobial peptide Dhvar-5 from
polymethylmethacrylate beads
2 Department
of Oral Cell Biology, Academic Centre
for Dentistry Amsterdam (ACTA), Vrije Universiteit, Amsterdam, The
Netherlands
3 Department
of Oral Biochemistry, Academic Centre
for Dentistry Amsterdam (ACTA), Vrije Universiteit, Amsterdam, The
Netherlands
4 Department of Orthopaedic
Surgery, Vrije Universiteit Medical Center (VUMC), Amsterdam
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