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Antimicrobial Agents and Chemotherapy, June 1998, p. 1355-1360, Vol. 42, No. 6
Department of Internal
Medicine1 and
Microbiology/Immunology,3 Medical
College of Virginia Campus of Virginia Commonwealth University,
Richmond, Virginia, and
AMBI, Inc., Tarrytown, New
York2
Received 2 January 1998/Returned for modification 5 March
1998/Accepted 25 March 1998
The emergence of clinical isolates of methicillin-resistant
Staphylococcus aureus with reduced susceptibility to
vancomycin has prompted a search for new and novel therapeutic agents
active against S. aureus. Lysostaphin, a peptidase produced
by Staphylococcus simulans, specifically cleaves the
glycine-glycine bonds unique to the interpeptide cross-bridge of the
S. aureus cell wall. The effectiveness of various regimens
of dosing with intravenous lysostaphin was compared to that of
vancomycin in the rabbit model of aortic valve endocarditis caused by a
clinical methicillin-resistant S. aureus isolate. All
animals were treated for a total of 3 days. The most active regimen,
lysostaphin given three times daily, produced sterile vegetations in 10 of 11 treated rabbits, with a mean reduction in vegetation bacterial
counts of 8.5 log10 CFU/g compared to the counts in the
untreated controls. In contrast, vancomycin given twice daily
sterilized no vegetations and reduced vegetation bacterial counts by
only 4.8 log10 CFU/g. Lysostaphin given once daily was less
effective, reducing mean vegetation bacterial counts by only 3.6 log10 CFU/g, but the combination of lysostaphin once daily
and vancomycin twice daily reduced the mean vegetation bacterial
density by 7.5 log10 CFU/g, a result that was significantly
better than that for either regimen alone (P < 0.05).
Lysostaphin was well tolerated by the rabbits, with no evidence of
immunological reactions following up to 9 weeks of intravenous
administration. We conclude that lysostaphin given alone or in
combination with vancomycin is more effective in the treatment of
experimental methicillin-resistant S. aureus aortic valve
endocarditis than vancomycin alone.
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Lysostaphin Treatment of Experimental
Methicillin-Resistant Staphylococcus aureus Aortic
Valve Endocarditis
*
Corresponding author. Mailing address: McGuire Veterans
Affairs Medical Center, 1201 Broad Rock Blvd., Section 111-C, Richmond, VA 23249. Phone: (804) 675-5018. Fax: (804) 675-5437. E-mail: CLIMO.MICHAEL{at}RICHMOND.VA.GOV or
MCLIMO{at}GEMS.VCU.EDU.
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