Document Detail


Successful therapy of experimental endocarditis caused by vancomycin-resistant Staphylococcus aureus with a combination of vancomycin and beta-lactam antibiotics.
MedLine Citation:
PMID:  16940087     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
VRS1 is the first isolated strain of vancomycin-resistant Staphylococcus aureus (VRSA) found to carry the vanA gene complex previously described in Enterococcus. Under vancomycin pressure, VRS1 makes aberrant cell walls consisting of stem tetrapeptide and depsipeptide that lack the terminal D-Ala-D-Ala residues targeted by vancomycin. Previous data have suggested that this aberrant cell wall is not cross-linked by PBP2a, the enzyme responsible for cell wall transpeptidation in the presence of beta-lactam antibiotics. We examined the efficacy of treating VRS1 with a combination of vancomycin and beta-lactam antibiotics in vitro and in vivo. We found that the MIC of oxacillin for VRS1 decreased from >256 microg/ml to <1 microg/ml in the presence of vancomycin. Using the rabbit model of endocarditis, we treated VRS1-infected rabbits with nafcillin alone, vancomycin alone, or a combination of nafcillin and vancomycin. Treatment with nafcillin in combination with vancomycin cleared bloodstream infections within 24 h and sterilized 12/13 spleens (92%), as well as 8/13 kidneys (62%), following 3 days of treatment. Mean aortic valve vegetation counts were reduced 3.48 log(10) CFU/g with the combination therapy (compared to untreated controls) and were significantly lower than with either vancomycin or nafcillin given alone. VRS1 was extremely virulent in this model, as no untreated rabbits survived the 3-day trial. Treatment of clinical infections due to VRSA with the combination of vancomycin and beta-lactams may be an option, based on these results.
Authors:
Paige M Fox; Russell J Lampen; Katrina S Stumpf; Gordon L Archer; Michael W Climo
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Antimicrobial agents and chemotherapy     Volume:  50     ISSN:  0066-4804     ISO Abbreviation:  Antimicrob. Agents Chemother.     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-08-30     Completed Date:  2006-11-28     Revised Date:  2013-06-07    
Medline Journal Info:
Nlm Unique ID:  0315061     Medline TA:  Antimicrob Agents Chemother     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2951-6     Citation Subset:  IM    
Affiliation:
Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Hunter Holmes McGuire Veteran Affairs Medical Center, Richmond, VA 23249, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Bacterial Agents / pharmacology*
Drug Therapy, Combination
Endocarditis, Bacterial / drug therapy*,  microbiology
Methicillin / pharmacology
Microbial Sensitivity Tests
Nafcillin / pharmacology*
Oxacillin / pharmacology
Rabbits
Staphylococcal Infections / drug therapy*,  microbiology
Staphylococcus aureus / drug effects,  isolation & purification*
Vancomycin / pharmacology*
Vancomycin Resistance*
Grant Support
ID/Acronym/Agency:
2 R01 AI035705-13/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Anti-Bacterial Agents; 1404-90-6/Vancomycin; 147-52-4/Nafcillin; 61-32-5/Methicillin; 66-79-5/Oxacillin
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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