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JAC Advance Access published online on February 7, 2006
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkl030
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
Received June 14, 2005
Revised October 11, 2005
Accepted January 21, 2006

Original article

Effects of prolonged vancomycin administration on methicillin-resistant Staphylococcus aureus (MRSA) in a patient with recurrent bacteraemia

George Sakoulas 1 *, Howard S. Gold 2, Robert A. Cohen 2, Lata Venkataraman 3, Robert C. Moellering 2, and George M. Eliopoulos 2

1 Westchester Medical Center and New York Medical College, Valhalla, NY, USA
2 Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA
3 Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA

* To whom correspondence should be addressed.
George Sakoulas, E-mail: george_sakoulas{at}nymc.edu


  Abstract

Objectives: To evaluate microbiological properties of methicillin-resistant

Staphylococcus aureus (MRSA) during prolonged vancomycin therapy.

Methods: We evaluated vancomycin susceptibility and heteroresistance, accessory gene regulator (agr) function, autolysis, biofilm production and in vitro vancomycin killing in serial MRSA bloodstream isolates obtained over a 30 month period from a patient with a chronic endovascular infection.

Results: Despite the fact that the MRSA in this patient had the same genetic background as other clinical glycopeptide intermediate-resistant S. aureus (GISA) isolates, vancomycin administered for 9 months, maintaining serum concentrations >10 mg/L, did not select for GISA. Minimal changes in vancomycin susceptibility were detected using agar dilution and population analysis methods. We noted increases in delta haemolysin production, autolysis and the bactericidal effects of vancomycin in vitro against the MRSA obtained after prolonged vancomycin suppressive therapy was discontinued.

Conclusions: Despite the lack of development of detectable resistance, MRSA exposed to vancomycin for prolonged periods may begin to develop vancomycin tolerance and decreased autolysis. In addition, suppression of agr function appears to end after vancomycin is stopped. Whether these changes are prerequisites for attenuated vancomycin efficacy and the development of glycopeptide resistance warrants further study. The development of vancomycin resistance may be more difficult under conditions where vancomycin serum concentrations are maintained >10 mg/L.

Keywords: glycopeptides; autolysis; biofilms; agr.
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