Heterogeneous Vancomycin-Intermediate Susceptibility Phenotype in Bloodstream Methicillin-Resistant Staphylococcus aureus Isolates from an International Cohort of Patients with Infective Endocarditis: Prevalence, Genotype, and Clinical Significance

Background. The significance of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) is unknown. Using a multinational collection of isolates from methicillin-resistant S. aureus (MRSA) infective endocarditis (IE), we characterized patients with IE with and without hVISA, and we genotyped the infecting strains. Methods. MRSA bloodstream isolates from 65 patients with definite IE from 8 countries underwent polymerase chain reaction (PCR) for 31 virulence genes, pulsed-field gel electrophoresis, and multilocus sequence typing. hVISA was defined using population analysis profiling. Results. Nineteen (29.2%) of 65 MRSA IE isolates exhibited the hVISA phenotype by population analysis profiling. Isolates from Oceania and Europe were more likely to exhibit the hVISA phenotype than isolates from the United States (77.8% and 35.0% vs 13.9%; P < .001). The prevalence of hVISA was higher among isolates with a vancomycin minimum inhibitory concentration of 2 mg/L (P = .026). hVISA-infected patients were more likely to have persistent bacteremia (68.4% vs 37.0%; P = .029) and heart failure (47.4% vs 19.6%; P = .033). Mortality did not differ between hVISA- and non-hVISA-infected patients (42.1% vs 34.8%, P = .586). hVISA and non-hVISA isolates were genotypically similar. Conclusions. In these analyses, the hVISA phenotype occurred in more than one-quarter of MRSA IE isolates, was associated with certain IE complications, and varied in frequency by geographic region.