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Antimicrobial Agents and Chemotherapy, April 2003, p. 1262-1266, Vol. 47, No. 4
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.4.1262-1266.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Vancomycin Treatment Failure Associated with Heterogeneous Vancomycin-Intermediate Staphylococcus aureus in a Patient with Endocarditis and in the Rabbit Model of Endocarditis

Matthew R. Moore,* Françoise Perdreau-Remington, and Henry F. Chambers

Division of Infectious Diseases, San Francisco General Hospital, and Department of Medicine, University of California, San Francisco, School of Medicine, San Francisco, California 94143

Received 27 August 2002/ Returned for modification 31 October 2002/ Accepted 31 December 2002

Heterogeneous resistance to vancomycin is thought to precede emergence of intermediate susceptibility to vancomycin in Staphylococcus aureus, but the clinical significance of heterogeneous resistance is unknown. Paired S. aureus isolates from a patient with endocarditis who relapsed after vancomycin treatment were tested for heterogeneous resistance to vancomycin. The pretreatment and the relapse clinical isolates (strains SF1 and SF2, respectively) were genotyped by pulsed-field gel electrophoresis. Susceptibility to vancomycin was assessed by the broth dilution method, population analysis, and time-kill studies and in the rabbit model of endocarditis. Strains SF1 and SF2 had similar genotypes, and the vancomycin MICs for the strains were <=2 µg/ml. SF2 exhibited heterogeneous resistance to vancomycin. Vancomycin eradicated SF1 in the rabbit model of endocarditis, while SF2 persisted at pretreatment levels. Vancomycin treatment failure in this patient with endocarditis was attributable to heterogeneous resistance to vancomycin.

* Corresponding author. Present address: Foodborne and Diarrheal Diseases Branch, Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Rd., NE, Mailstop D-63, Atlanta, GA 30333. Phone: (404) 371-5410. Fax: (404) 371-5444. E-mail: mmoore4{at}cdc.gov.

Antimicrobial Agents and Chemotherapy, April 2003, p. 1262-1266, Vol. 47, No. 4
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.4.1262-1266.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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