title: Vancomycin-resistant Enterococcal Bloodstream Infections in Hematopoietic Stem Cell Transplant Recipients and Patients with Hematologic Malignancies: Impact of Daptomycin MICs of 3 to 4 mg/L.
abstract: Case reports of treatment failure with standard-dose daptomycin (6 mg/kg) have recently surfaced in vancomycin-resistant Enterococcus (VRE) bloodstream infection (BSI) episodes with daptomycin MICs of 3 to 4 mg/L. The clinical implications of daptomycin MICs of 3 to 4 mg/L in VRE BSIs have not been elucidated.
  
  
  
  We performed a single institutional retrospective analysis of adult stem cell transplant recipients and patients with hematologic malignancies diagnosed with VRE BSI from 2006 to 2014 and compared outcomes between those with daptomycin MICs of 3 to 4 mg/L those with 2 mg/L, as determined by Etest.
  
  
  
  Forty-two daptomycin-treated VRE BSI episodes, all due to Enterococcus faecium were identified; 19 episodes with daptomycin MICs of 3 to 4 mg/L and 23 episodes with a daptomycin MIC of 2 mg/L. Patients in the higher daptomycin MIC group were more likely to be male, to be stem cell transplant recipients, and to have received high-dose daptomycin treatment (>6 mg/kg). In unadjusted analyses, microbiological failure in the daptomycin MICs 3 to 4 mg/L versus 2 mg/L groups (odds ratio = 1.79, 95% CI, 0.52-6.11; P = 0.35), the median duration of bacteremia (4 days in daptomycin MICs 3-4 mg/L vs 3 days in daptomycin MIC 2 mg/L; P = 0.18) and all-cause 30-day mortality (21% in daptomycin MICs 3-4 mg/L vs 35% in daptomycin MIC 2 mg/L group; P = 0.49) were not different. In adjusted analyses, the association between higher Pitt bacteremia scores and all-cause 30-day mortality was statistically significant (P = 0.0006), whereas the association between daptomycin MICs of 3 to 4 mg/L and all-cause 30-day mortality approached statistical significance (P = 0.06).
  
  
  
  Duration of bacteremia and microbiological failure rates did not differ by daptomycin MICs in VRE BSI episodes in our patients, composed of adult stem cell transplant recipients and patients with hematologic malignancies. There was a nonsignificant trend in multivariable analysis suggesting that all-cause 30-day mortality was lower in patients whose VRE bloodstream isolates were with daptomycin MICs of 3 to 4 mg/L.
authors: Division of Infectious Diseases, University of North Carolina, Chapel Hill, North Carolina. Electronic address: pearlie_chong@med.unc.edu.
authors: Pearlie P
authors: PP
authors: Chong
authors: Division of Infectious Diseases, University of North Carolina, Chapel Hill, North Carolina.
authors: David
authors: D
authors: van Duin
authors: Biostatistics and Bioinformatics Core, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
authors: Ananta
authors: A
authors: Bangdiwala
authors: Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina.
authors: Anastasia
authors: A
authors: Ivanova
authors: Division of Epidemiology, College of Public Health, The Ohio State University, Columbus, Ohio.
authors: William C
authors: WC
authors: Miller
authors: Division of Infectious Diseases, University of North Carolina, Chapel Hill, North Carolina; Hospital Epidemiology, UNC Health Care, Chapel Hill, North Carolina.
authors: David J
authors: DJ
authors: Weber
authors: Clinical Microbiology-Immunology Laboratories, University of North Carolina Health Care and Department of Pathology-Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
authors: Peter H
authors: PH
authors: Gilligan
authors: Division of Hematology/Oncology and UNC Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina.
authors: Thomas C
authors: TC
authors: Shea
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy*; D017576:Daptomycin / Q000627:therapeutic use*; D016984:Enterococcus faecium / Q000187:drug effects; D005260:Female; D019337:Hematologic Neoplasms / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D012189:Retrospective Studies; D014640:Vancomycin / Q000627:therapeutic use*; D020713:Vancomycin Resistance / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin; D017576:Daptomycin
keywords: Enterococcus faecium; VRE; bacteremia; daptomycin; neutropenia; vancomycin-resistant enterococci