Relevance of vancomycin-intermediate susceptibility and heteroresistance in methicillin-resistant Staphylococcus aureus bacteraemia

Objectives: To assess the relevance of vancomycin-intermediate susceptibility (VISA) and heteroresistance (hVISA) in methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia. Methods: We determined vancomycin MICs for 371 saved MRSA blood isolates (2002-03; 2005-06) by Etest and broth microdilution (BMD), screened for hVISA (Etest methods), determined the population analysis profile (PAP)/AUC for isolates with suspected reduced susceptibility (MICs >2 mg/L and/or hVISA-screen-positive versus Mu3 (hVISA control), and stratified patient characteristics and outcome according to susceptibility phenotype: VISA (PAP/AUC >1.3), hVISA (PAP/AUC 0.9-1.3), and susceptible (S-MRSA; PAP/AUC<0.9). Results: PAP/AUC revealed 6 (1.6%) VISA and 30 (8.1%) hVISA phenotypes. The Etest MIC was above the susceptibility cut-off (2 mg/L) for all VISA isolates, whereas the BMD MIC was within the susceptibility range in two (33.3%) instances. Eight hVISA isolates (26.7%) with MICs of 2 mg/L were hVISA-screen negative. SCCmec typing revealed SCCmec II in 100% of VISA, 86.7% of hVISA and 75.5% of S-MRSA isolates (P=0.04). Prior vancomycin use was documented in 100% of VISA, 73.3% of hVISA and 52.2% of S-MRSA cases (P=0.002). Outcome (compared in 243 vancomycin-treated patients with MICs of 2 mg/L) revealed longer time to clearance in VISA cases [12.1±13.1 days versus 3.3±3.9 (hVISA) and 3.7±5.1 (S-MRSA); P=0.001], more frequent endocarditis [33.3% versus 9.1% (hVISA; P=0.1) and 4.2% (S-MRSA; P=0.001)] and attributable mortality [33.3% versus 9.1% (hVISA; P=0.1) and 8.4% (S-MRSA); P=0.08]. Conclusions: No adverse outcome was documented with hVISA phenotype, whereas VISA contributed to vancomycin treatment failure. VISA and hVISA appear to emerge in SCCmec II isolates among vancomycinexposed patients and are better detected by Etest.