title: Relevance of vancomycin-intermediate susceptibility and heteroresistance in methicillin-resistant Staphylococcus aureus bacteraemia.
abstract: OBJECTIVE
  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 vancomycin-exposed patients and are better detected by Etest.
authors.affiliation: Department of Medicine, St John Hospital and Medical Center, Grosse Pointe Woods, MI, USA. riad.khatib@stjohn.org
authors.forename: Riad
authors.initials: R
authors.lastname: Khatib
authors.forename: Jinson
authors.initials: J
authors.lastname: Jose
authors.forename: Adina
authors.initials: A
authors.lastname: Musta
authors.forename: Mamta
authors.initials: M
authors.lastname: Sharma
authors.forename: Mohamad G
authors.initials: MG
authors.lastname: Fakih
authors.forename: Leonard B
authors.initials: LB
authors.lastname: Johnson
authors.forename: Kathleen
authors.initials: K
authors.lastname: Riederer
authors.forename: Stephen
authors.initials: S
authors.lastname: Shemes
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology*; D005260:Female; D006801:Humans; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D016896:Treatment Outcome; D014640:Vancomycin / Q000494:pharmacology* / Q000627:therapeutic use; D020713:Vancomycin Resistance
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin