title: Is there a clinical association of vancomycin MIC creep, agr group II locus, and treatment failure in MRSA bacteremia?
abstract: BACKGROUND
  The association of vancomycin treatment failure with minimum inhibitory concentration (MIC) creep is concerning, as most isolates are still considered to be in the susceptible range. Several studies have suggested that the accessory gene regulator (agr) group II polymorphism is predictive of vancomycin treatment failure. We assessed the associations between increased vancomycin MIC, agr group II locus, and vancomycin treatment failure in Methicillin-resistant Staphylococcus aureus (MRSA) bacteremias.
  
  
  METHODS
  MRSA isolates from 99 inpatient bacteremias were studied. Susceptibility testing was conducted by an automated method (MicroScan) and by the gradient diffusion method (E-test). Vancomycin MICs were stratified into 3 groups for analysis: MIC ≤ 1, MIC > 1 but ≤ 2, and MIC >2 μg/mL. Strains were typed by repetitive-polymerase chain reaction analysis and the agr locus was identified by multiplex polymerase chain reaction. Failure of vancomycin treatment was defined as persistent bacteremia after 72 hours, death at 30 days, or treatment change due to clinical failure.
  
  
  RESULTS
  Among 99 bacteremic patients, there were 82 agr group II and 15 agr group I isolates. There was no relationship between higher vancomycin MICs and isolate agr II loci (42 of 82) (P=0.59). Earlier vancomycin exposure was significantly associated with increased MIC (P=0.03). Vancomycin treatment failure was observed in 12 patients: 3 required an alternate regimen, 4 had persistent positive cultures, and 5 whose deaths were attributable to MRSA infection. Survival in agr group II was 57 of 82 (69%) versus agr group I in which it was 14 of 15 (93%), (P=0.06).
  
  
  CONCLUSIONS
  We did not identify any significant association between MIC creep and vancomycin failure or between higher vancomycin MICs and agr group II. However, a higher mortality was seen in agr group II than agr group I.
authors.affiliation: Division of Infectious diseases, William Beaumont Hospital, Royal Oak, MI, USA. desacj@ccf.org
authors.forename: Jorgelina T
authors.initials: JT
authors.lastname: de Sanctis
authors.forename: Aditi
authors.initials: A
authors.lastname: Swami
authors.forename: Kara
authors.initials: K
authors.lastname: Sawarynski
authors.forename: Ludmyla
authors.initials: L
authors.lastname: Gerasymchuk
authors.forename: Kim
authors.initials: K
authors.lastname: Powell
authors.forename: Barbara
authors.initials: B
authors.lastname: Robinson-Dunn
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Carpenter
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Sims
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D001426:Bacterial Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000235:genetics*; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D015534:Trans-Activators / Q000235:genetics*; D017211:Treatment Failure; D014640:Vancomycin / Q000494:pharmacology / Q000627:therapeutic use*; D020713:Vancomycin Resistance / Q000235:genetics
chemical_list: C095698:Agr protein, Staphylococcus aureus; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015534:Trans-Activators; D014640:Vancomycin