Comparison of the clinical features, bacterial genotypes and outcomes of patients with bacteraemia due to heteroresistant vancomycin-intermediate Staphylococcus aureus and vancomycin-susceptible S. aureus

Abstract

We compared the clinical characteristics and outcomes of, and the bacterial genotypes in, patients with bacteraemia due to heteroresistant vancomycin-intermediate Staphylococcus aureus (hVISA) and vancomycin-susceptible S. aureus (VSSA). A total of 268 consecutive patients with methicillin-resistant S. aureus (MRSA) bacteraemia were prospectively enrolled. All isolates were selected on the first day of bacteraemia and subjected to population analysis profiling for identification of hVISA phenotype and PCR analysis for 41 virulence factors. Of 268 MRSA isolates, 101 (37.7%) were identified as hVISA. Overall mortality was similar in hVISA- and VSSA-infected patients (45/101 versus 65/167; P = 0.36). The following factors were independently associated with the presence of hVISA: a vancomycin MIC ≥2 mg/L by Etest [adjusted OR (aOR), 9.98; 95% CI, 4.22-23.59], rifampicin resistance (aOR, 5.74; 95% CI, 1.35-24.37), prior vancomycin therapy (aOR, 3.04; 95% CI, 1.49-6.17) and use of immunosuppressive therapy (aOR, 2.41; 95% CI, 1.12-5.17). Among patients with hVISA, bacteraemia was more likely to persist for ≥7 days in patients with an initial vancomycin trough <15 mg/L than in those with an initial trough ≥15 mg/L (13/34 versus 5/35; P = 0.02). The hVISA and VSSA isolates were genotypically similar. The hVISA phenotype was present in more than one-third of MRSA isolates and was independently associated with several baseline factors. Although this phenotype did not affect patient outcomes, our results indicate that targeting an initial vancomycin trough of 15-20 mg/L may be beneficial in patients with hVISA bacteraemia.