title: Factors influencing time to vancomycin-induced clearance of nonendocarditis methicillin-resistant Staphylococcus aureus bacteremia: role of platelet microbicidal protein killing and agr genotypes.
abstract: BACKGROUND
  Vancomycin susceptibility, the accessory gene global regulator (agr) genotype and function, staphylococcal cassette chromosome (SCC) mec type, and susceptibility to cationic thrombin-induced platelet microbicidal protein 1 (tPMP-1) have been individually predictive of duration of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. This investigation evaluated the interrelationship of these factors with time to clearance of MRSA bacteremia during vancomycin therapy in patients without endocarditis.
  
  
  METHODS
  Vancomycin minimum inhibitory concentration and in vitro killing, agr function (delta-hemolysin activity), agr group, SCCmec type, and survival in tPMP-1 killing assays were determined for 29 MRSA bacteremia isolates.
  
  
  RESULTS
  Increased resistance to tPMP-1 killing was observed with agr group III MRSA (P = .025) and MRSA with reduced or absent agr function (P = .023). The median time to clearance of MRSA bacteremia was earlier for agr group III (3 days) versus group I (10.5 days) or II (15 days) (P = .001). In multivariate analysis, agr group II, reduced tPMP-1 killing in vitro, and prior vancomycin exposure were significant independent predictors of longer MRSA bacteremia duration.
  
  
  CONCLUSIONS
  Specific genotypic, phenotypic, and clinical parameters appear to correlate with persistent MRSA bacteremia. The interrelationship of these and other factors probably contributes to vancomycin-mediated clearance of MRSA bacteremia.
authors.affiliation: Cubist Pharmaceuticals, Lexington, Massachusetts, USA.
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Moise
authors.forename: Alan
authors.initials: A
authors.lastname: Forrest
authors.forename: Arnold S
authors.initials: AS
authors.lastname: Bayer
authors.forename: Yan Q
authors.initials: YQ
authors.lastname: Xiong
authors.forename: Michael R
authors.initials: MR
authors.lastname: Yeaman
authors.forename: George
authors.initials: G
authors.lastname: Sakoulas
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016470:Bacteremia / Q000188:drug therapy / Q000382:microbiology*; D001426:Bacterial Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D046915:Penicillin-Binding Proteins; D015534:Trans-Activators / Q000235:genetics*; D014640:Vancomycin / Q000494:pharmacology*; D001620:beta-Thromboglobulin / Q000502:physiology*
chemical_list: C095698:Agr protein, Staphylococcus aureus; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C061615:PPBP protein, human; D046915:Penicillin-Binding Proteins; D015534:Trans-Activators; D001620:beta-Thromboglobulin; C487789:mecA protein, Staphylococcus aureus; D014640:Vancomycin