BACKGROUND: Coagulase-negative staphylococci (CNS) are the major cause of nosocomial bloodstream infection. Emergence of vancomycin resistance among CNS is a serious public health concern, because CNS usually are multidrug-resistant, and glycopeptide antibiotics, among which only vancomycin is available in the United States, are the only remaining effective therapy. In this report, we describe the first bloodstream infection in the United States associated with a Staphylococcus epidermidis strain with decreased susceptibility to vancomycin. METHODS: We reviewed the hospital's microbiology records for all CNS strains, reviewed the patient's medical and laboratory records, and obtained all available CNS isolates with decreased susceptibility to vancomycin. Blood cultures were processed and CNS isolates identified by using standard methods; antimicrobial susceptibility was determined by using minimum inhibitory concentration (MIC) and disk-diffusion methods. Nares cultures were obtained from exposed healthcare workers (HCWs) to identify possible colonization by CNS with decreased susceptibility to vancomycin. RESULTS: The bloodstream infection by an S. epidermidis strain with decreased susceptibility to vancomycin occurred in a 49-year-old woman with carcinoma. She had two blood cultures positive for CNS; both isolates were S. epidermidis. Although susceptible to vancomycin by the disk-diffusion method (16-17 mm), the isolates were intermediate by MIC (8-6 microg/mL). The patient had received an extended course of vancomycin therapy; she died of her underlying disease. No HCW was colonized by CNS with decreased susceptibility to vancomycin. CONCLUSIONS: This is the first report in the United States of bloodstream infection due to S. epidermidis with decreased susceptibility to vancomycin. Contact precautions likely played a role in preventing nosocomial transmission of this strain, and disk-diffusion methods may be inadequate to detect CNS with decreased susceptibility to vancomycin.