title: Vancomycin heteroresistance is associated with reduced mortality in ST239 methicillin-resistant Staphylococcus aureus blood stream infections.
abstract: BACKGROUND
  Despite hVISA infections being associated with vancomycin treatment failure, no previous study has been able to detect a mortality difference between heteroresistant vancomycin intermediate Staphylococcus aureus (hVISA) and vancomycin susceptible Staphylococcus aureus (VSSA) bloodstream infections (BSI).
  
  
  METHODS
  Consecutive methicillin-resistant S. aureus (MRSA) BSI episodes between 1996 and 2008 were reviewed. Patient demographics, clinical presentation, treatment and overall mortality at 30 days were extracted from the medical records. All isolates underwent vancomycin minimum inhibitory concentration (VMIC) testing by broth microdilution and Etest. hVISA was confirmed by population analysis profiling using the area under the curve method (PAP-AUC).
  
  
  RESULTS
  401 evaluable MRSA BSI episodes were identified over the 12 years. Of these, 46 (11.5%) and 2 (0.5%) were confirmed as hVISA and VISA by PAP-AUC respectively. hVISA predominantly occurred in ST239-like MRSA isolates with high VMIC (2 mg/L). Compared to VSSA, hVISA was associated with chronic renal failure (p<0.001), device related infections (haemodialysis access) (p<0.001) and previous vancomycin usage (p = 0.004). On multivariate analysis, independent predictors of mortality included age, presence of multiple co-morbidities, principal diagnosis, transit to ICU and severity of illness while infection related surgery and hVISA phenotype were associated with increased survival.
  
  
  CONCLUSIONS
  The presence of hVISA is dependent on the appropriate interplay between host and pathogen factors. hVISA in ST239 MRSA is an independent predictor of survival. Whether these findings would be replicated across all MRSA clones is unknown and warrants further study.
authors.affiliation: Department of Microbiology and Infectious Diseases, Sydney South West Pathology Service-Liverpool Hospital, Sydney, New South Wales, Australia. Sebastian.vanHal@sswahs.nsw.gov.au
authors.forename: Sebastiaan J
authors.initials: SJ
authors.lastname: van Hal
authors.forename: Mark
authors.initials: M
authors.lastname: Jones
authors.forename: Iain B
authors.initials: IB
authors.lastname: Gosbell
authors.forename: David L
authors.initials: DL
authors.lastname: Paterson
mesh_terms: D000368:Aged; D001315:Australia; D016470:Bacteremia / Q000188:drug therapy* / Q000401:mortality*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000472:pathogenicity; D008875:Middle Aged; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000401:mortality*; D016896:Treatment Outcome; D014640:Vancomycin / Q000494:pharmacology* / Q000627:therapeutic use*; D020713:Vancomycin Resistance / Q000187:drug effects*
chemical_list: D014640:Vancomycin