title: Vancomycin-resistant enterococcal bacteraemia and daptomycin: are higher doses necessary?
abstract: BACKGROUND
  The MIC corresponding to daptomycin susceptibility for vancomycin-resistant enterococci (VRE) is ≤ 4 mg/L. Based on the concentration-dependent killing properties of daptomycin, there may be concern about achieving adequate concentrations when the MIC approaches the upper end of the susceptible range (3-4 mg/L). Higher doses of daptomycin may be needed to treat VRE isolates with higher MICs.
  
  
  METHODS
  We conducted a single-centre retrospective chart review of adult cases with VRE bacteraemia who received daptomycin as initial therapy. The primary outcome was time to microbiological cure (TMC) between standard doses (≤ 6 mg/kg) and high doses (> 6 mg/kg) of daptomycin and whether TMC differed based on MICs. The secondary outcome evaluated the daptomycin MIC distribution and assessed whether recent exposure to vancomycin was associated with higher daptomycin MICs.
  
  
  RESULTS
  Forty-six cases were included in the primary analysis and 60.9% of patients were neutropenic. The two dose groups differed in the baseline characteristics of age, body mass index, blood culture source and catheter removal. Median TMC was 2 days for both dose groups. There was no significant difference in TMC between MIC subgroups of ≤ 2 mg/L versus >2 and ≤ 4 mg/L. For the secondary analysis 227 VRE isolates were evaluated and 62% had daptomycin MICs of 3-4 mg/L. Each daptomycin MIC group had a similar incidence of prior vancomycin exposure.
  
  
  CONCLUSIONS
  Based on this retrospective review we did not observe a difference in TMC based on daptomycin dose and MIC; however, there were various limitations to this study, and the study was not powered to detect a difference in TMC. Also, prior vancomycin exposure did not appear to influence daptomycin MICs. The frequency of daptomycin MICs of 3-4 mg/L reported in this study is higher than those reported in the literature.
authors.affiliation: Department of Pharmacy, Hackensack University Medical Center, Hackensack, NJ, USA. esther.aizenberg@gmail.com
authors.forename: Esther A
authors.initials: EA
authors.lastname: King
authors.forename: Dorothy
authors.initials: D
authors.lastname: McCoy
authors.forename: Samit
authors.initials: S
authors.lastname: Desai
authors.forename: Themba
authors.initials: T
authors.lastname: Nyirenda
authors.forename: Keri
authors.initials: K
authors.lastname: Bicking
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology; D017576:Daptomycin / Q000008:administration & dosage* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D016983:Enterococcus / Q000187:drug effects*; D013293:Enterococcus faecalis / Q000187:drug effects; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009503:Neutropenia / Q000150:complications; D012189:Retrospective Studies; D017211:Treatment Failure; D016896:Treatment Outcome; D014640:Vancomycin / Q000627:therapeutic use; D020713:Vancomycin Resistance
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin; D017576:Daptomycin