title: Clinical Outcomes of Daptomycin for Vancomycin-resistant Enterococcus Bacteremia.
abstract: OBJECTIVE
  In light of recent evidence suggesting enhancement of daptomycin activity against vancomycin-resistant Enterococcus (VRE) by ampicillin and other β-lactam antibiotics, we evaluated the safety profile and clinical efficacy of daptomycin with and without concomitant β-lactam antimicrobials in the treatment of VRE (faecium or faecalis) bacteremia from multiple centers across the United States.
  
  
  METHODS
  Data were collected retrospectively as part of a larger multicenter registry (The Cubicin Outcomes Registry and Experience). Efficacy and clinical outcomes in patients with VRE bacteremia who received at least 3 days of daptomycin with or without concomitant β-lactams were analyzed. Although all the cases involved daptomycin-susceptible VRE, additional analysis was performed to examine whether the adjunctive β-lactam would play a more pivotal role in cases where the daptomycin MIC was in the upper limit of the susceptibility range, indicating that daptomycin monotherapy efficacy may be relatively compromised compared with cases with lower daptomycin MICs.
  
  
  RESULTS
  Two hundred sixty-two patients from 33 hospitals were evaluated. Most patients had at least one significant comorbidity, such as solid-organ or bone marrow transplantation (16%), neutropenia (36%), dialysis dependency (20%), or critical illness (36%) requiring care in an intensive care unit. Overall treatment success was 86% (n = 225/262), and treatment success for patients taking concomitant β-lactams was 86% (n = 105/122). Logistic regression identified treatment failure to be associated with sepsis (odds ratio = 3.42; P = 0.009) and an elevated daptomycin MIC (3-4 µg/mL) (odds ratio = 3.23, P = 0.013). No significant increase in clinical failure was seen among patients with elevated daptomycin MIC who received concomitant β-lactam therapy (clinical success, 88% vs 79% for MIC ≤2 vs 3-4 µg/mL, respectively; P = 0.417). Of 262 patients, 33 (13%) experienced ≥1 adverse event possibly related to daptomycin (increased creatine kinase in 8 patients).
  
  
  CONCLUSIONS
  Overall, daptomycin was effective and well tolerated for VRE bacteremia, with lower effectiveness noted with daptomycin MIC of 3 to 4 µg/mL. Concomitant β-lactam therapy with daptomycin may improve clinical outcomes in this setting. Further studies are needed to characterize the potential benefit of concomitant β-lactams with daptomycin.
authors.affiliation: Department of Medical Affairs, Merck and Co., Inc., Kenilworth, New Jersey. Electronic address: pamela.moise@merck.com.
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Moise
authors.affiliation: Department of Pharmacology and Drug Discovery, University of California San Diego School of Medicine, La Jolla, California.
authors.forename: George
authors.initials: G
authors.lastname: Sakoulas
authors.affiliation: Infectious Disease Clinical Outcomes Research (ID-CORE), Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California; David Geffen School of Medicine at the University of California, Los Angeles, California.
authors.forename: James A
authors.initials: JA
authors.lastname: McKinnell
authors.affiliation: Department of Medical Affairs, Merck and Co., Inc., Kenilworth, New Jersey.
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Lamp
authors.affiliation: Department of Medical Affairs, Merck and Co., Inc., Kenilworth, New Jersey.
authors.forename: Daryl D
authors.initials: DD
authors.lastname: DePestel
authors.affiliation: Department of Biostatistics, Merck and Co., Inc., Kenilworth, New Jersey.
authors.forename: Min J
authors.initials: MJ
authors.lastname: Yoon
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, Henry Ford Hospital, Detroit, Michigan; Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Katherine
authors.initials: K
authors.lastname: Reyes
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, Henry Ford Hospital, Detroit, Michigan; Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Zervos
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy*; D017576:Daptomycin / Q000627:therapeutic use*; D016983:Enterococcus; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D019233:Retreatment; D012189:Retrospective Studies; D014481:United States; D014640:Vancomycin / Q000627:therapeutic use*; D020713:Vancomycin Resistance; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin; D017576:Daptomycin
keywords: MIC, enterococci; VRE bacteremia; daptomycin; enterococcus; β-lactam