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We studied the molecular epidemiology of vancomycin-resistant enterococci (VRE) isolated in northeast Ohio during 1996 and examined the association between isolation of VRE from samples other than stool and antimicrobial purchases for five Cleveland hospitals. Susceptibility testing and pulsed-field gel electrophoresis were used to analyze 363 isolates from individual patients from 13 hospitals. Susceptibility testing indicated that 287 strains (79%) expressed the VanB phenotype and 76 (21%) expressed the VanA phenotype. The outbreak was polyclonal, with 30 total genotypes. Both VanA and VanB VRE demonstrated multiple genotypes. One genotype was present in all hospitals, suggesting spread between hospitals. For five teaching hospitals, rates of isolation from non-stool sources and from blood correlated positively with purchases of ticarcillin/clavulanic acid (P = .005). In summary, this outbreak demonstrates transmission of VRE between several hospitals in a geographic region and suggests that use of certain β-lactam antibiotics may be associated with an increased prevalence of VRE.