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Journal of Clinical Microbiology, April 2003, p. 1687-1693, Vol. 41, No. 4
0095-1137/03/$08.00+0     DOI: 10.1128/JCM.41.4.1687-1693.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Evolution of a Vancomycin-Intermediate Staphylococcus aureus Strain In Vivo: Multiple Changes in the Antibiotic Resistance Phenotypes of a Single Lineage of Methicillin-Resistant S. aureus under the Impact of Antibiotics Administered for Chemotherapy

K. Sieradzki,1 T. Leski,1 J. Dick,2 L. Borio,2 and A. Tomasz1*

The Rockefeller University, New York, New York 10021,1 John Hopkins Medical Institutions, Baltimore, Maryland 212872

Received 2 October 2002/ Returned for modification 29 November 2002/ Accepted 7 January 2003

A number of methicillin-resistant Staphylococcus aureus (MRSA) isolates were recovered over a period of several weeks from blood samples and from the heart valve of a patient who underwent extensive vancomycin chemotherapy for persistent S. aureus bacteremia. Consecutive isolates showed gradually decreasing growth rates during in vitro cultivation and increasing vancomycin MICs, from an MIC of 1 µg/ml for the initial isolate to an MIC of 8 µg/ml for the final MRSA isolates, which also became tolerant to vancomycin. Major changes were observed in the oxacillin resistance phenotype of several of the isolates—apparently related to in vivo exposure to imipenem, which was also used during a period of chemotherapy. Both the gradually increasing vancomycin MICs and the changes in oxacillin resistance could be reproduced by appropriate exposure of the initial MRSA isolate to antibiotics in vitro. All isolates had the same pulsed-field gel electrophoresis pattern, spaA type, and multilocus sequence type (MLST), which was identified as a single-locus variant of ST5, the MLST characteristic of previously characterized MRSA isolates with reduced susceptibility to vancomycin in the United States and Japan.


* Corresponding author. Mailing address: The Rockefeller University, 1230 York Ave., New York, NY 10021. Phone: (212) 327-8277. Fax: (212) 327-8688. E-mail: tomasz{at}mail.rockefeller.edu.


Journal of Clinical Microbiology, April 2003, p. 1687-1693, Vol. 41, No. 4
0095-1137/03/$08.00+0     DOI: 10.1128/JCM.41.4.1687-1693.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.




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