title: Time Is of the Essence: The Impact of Delayed Antibiotic Therapy on Patient Outcomes in Hospital-Onset Enterococcal Bloodstream Infections.
abstract: With increasing prevalence of vancomycin-resistant enterococci (VRE), appropriate antibiotic therapy for enterococcal bloodstream infections (EBSI) can be delayed. Data regarding the impact of delayed therapy on EBSI outcomes are conflicting, and the time delay most strongly associated with poor outcomes has not been defined.
  
  
  
  This was a single-center, retrospective cohort study of adult, nonneutropenic patients with hospital-onset EBSI from 2010 to 2014. Classification and regression tree (CART) analysis was used to determine the delay in appropriate therapy most predictive of 30-day mortality. Appropriate therapy was defined as antibiotic therapy to which the enterococci and copathogen, where applicable, were susceptible. Outcomes and clinical characteristics were compared between patients receiving early or delayed therapy, defined by CART timepoint. Poisson regression was employed to determine the independent association of delayed therapy on 30-day mortality and predictors of delayed therapy.
  
  
  
  Overall, 190 patients were included. A breakpoint in time to appropriate therapy was identified at 48.1 hours, where 30-day mortality was substantially increased (14.6% vs 45.3%; P < .001). Patients receiving appropriate therapy after 48.1 hours also experienced higher in-hospital mortality and longer EBSI duration. After adjustment for severity of illness and comorbidity, delayed therapy ≥48.1 hours was associated with a 3-fold increase in 30-day mortality (risk ratio, 3.16 [95% confidence interval, 1.96-5.09]). Vancomycin resistance was the only independent predictor of delayed therapy.
  
  
  
  In patients with hospital-onset EBSI, receipt of appropriate therapy within the first 48 hours was associated with reduced mortality, underscoring the potential role of rapid diagnostic testing for early identification of VRE.
authors.affiliation: Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University.
authors.forename: Evan J
authors.initials: EJ
authors.lastname: Zasowski
authors.affiliation: Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University.
authors.forename: Kimberly C
authors.initials: KC
authors.lastname: Claeys
authors.affiliation: Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University.
authors.forename: Abdalhamid M
authors.initials: AM
authors.lastname: Lagnf
authors.affiliation: Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University.|Department of Pharmacy Services, Henry Ford Hospital.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Davis
authors.affiliation: Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University.|Department of Medicine, Division of Infectious Diseases, School of Medicine, Wayne State University.|Department of Pharmacy Services, Detroit Medical Center, Michigan.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rybak
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy / Q000453:epidemiology / Q000401:mortality; D003428:Cross Infection / Q000188:drug therapy / Q000453:epidemiology / Q000401:mortality; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy / Q000453:epidemiology / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D012189:Retrospective Studies; D061665:Time-to-Treatment; D016896:Treatment Outcome; D065507:Vancomycin-Resistant Enterococci
chemical_list: D000900:Anti-Bacterial Agents
keywords: Enterococcus faecalis; Enterococcus faecium; appropriate antibiotic therapy; bacteremia; vancomycin-resistant enterococci