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JAC Advance Access published online on November 27, 2007
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkm445
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© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

Microbiological effects of prior vancomycin use in patients with methicillin-resistant Staphylococcus aureus bacteraemia

Pamela A. Moise1, Davida S. Smyth2, Nadia El-Fawal3, Ashley D. Robinson2, Patricia N. Holden4, Alan Forrest4 and George Sakoulas3,*

1 University of the Pacific School of Pharmacy and VA San Diego Healthcare System, San Diego, CA 92161, USA 2 Department of Microbiology and Immunology, New York Medical College, Valhalla, NY, USA 3 Westchester Medical Center and Division of Infectious Diseases, New York Medical College, Valhalla, NY 10595, USA 4 SUNY Buffalo School of Pharmacy, Buffalo, NY 14260, USA

Received 10 September 2007; returned 27 September 2007; revised 18 October 2007; accepted 19 October 2007

* Corresponding author. Tel: +1-914-493-8865; Fax: +1-914-594-4673; E-mail: george_sakoulas{at}nymc.edu

Background: We sought to determine whether prior vancomycin use (within 30 days) in patients who develop methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia is associated with isolates of reduced vancomycin susceptibility and killing in vitro.

Methods: Thirty-eight MRSA from previously vancomycin-treated patients and 43 MRSA from vancomycin-naive patients were evaluated by vancomycin and daptomycin CLSI broth microdilution and killing assays. PCR was used to determine accessory gene regulator (agr) type and staphylococcal cassette chromosome mec (SCCmec) type, and nucleotide sequencing was used to determine spa type.

Results: Vancomycin MICs were 0.5, 1.0 and 2.0 mg/L for 19, 55 and 7 isolates, respectively. Daptomycin MICs were 0.25, 0.5, 1.0 and 2.0 mg/L for 4, 50, 26 and 1 isolate, respectively. The agr-type distribution was agr group II (59%), group I (25%) and group III (16%); 90% harboured SCCmec II. The genetic background extrapolated by spa-typing showed that 58% of the isolates were of clonal complex 5. MRSA bloodstream isolates from patients who had received vancomycin within the preceding 30 days had a significantly decreased vancomycin killing at 24 h in vitro (median log10 decrease, 3.1 versus 2.2 cfu/mL; P = 0.021) and a significantly higher vancomycin MIC than isolates obtained from patients without that history (P = 0.002).

Conclusions: MRSA bloodstream isolates from patients recently treated with vancomycin may demonstrate reduced susceptibility and increased tolerance to vancomycin in vitro. Given that such microbiological phenotypes have been associated with reduced vancomycin efficacy, consideration may be given to alternative Gram-positive antimicrobial therapy in patients who have recently been treated with vancomycin.

Key Words: glycopeptides , daptomycin , MRSA , resistance


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