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Vancomycin-resistant enterococcal bacteraemia and daptomycin: are higher doses necessary?

Esther A King1, Dorothy McCoy, Samit Desai

  • 1Department of Pharmacy, Hackensack University Medical Center, Hackensack, NJ, USA. esther.aizenberg@gmail.com

The Journal of Antimicrobial Chemotherapy
|June 24, 2011
PubMed
Abstract

Insights

This study found no difference in microbiological cure time for vancomycin-resistant enterococci (VRE) treated with standard or high-dose daptomycin, regardless of minimum inhibitory concentration (MIC). Prior vancomycin exposure did not affect daptomycin MICs.

Area of Science:

  • Infectious Diseases
  • Pharmacology
  • Clinical Microbiology

Background:

  • Vancomycin-resistant enterococci (VRE) infections pose a significant challenge, with daptomycin susceptibility defined by a minimum inhibitory concentration (MIC) of ≤ 4 mg/L.
  • Daptomycin's concentration-dependent killing necessitates adequate drug exposure, raising concerns for VRE isolates with MICs nearing the susceptible threshold (3-4 mg/L).
  • Higher daptomycin doses may be considered for VRE with elevated MICs.

Purpose of the Study:

  • To compare time to microbiological cure (TMC) in adult VRE bacteremia patients receiving standard (≤ 6 mg/kg) versus high (> 6 mg/kg) daptomycin doses.
  • To determine if TMC varied based on daptomycin MIC values.
  • To evaluate daptomycin MIC distribution and the association between prior vancomycin exposure and higher daptomycin MICs.

Main Methods:

  • A single-center retrospective chart review of adult VRE bacteremia cases treated with daptomycin as initial therapy.
  • Primary outcome: TMC comparison between standard and high daptomycin dose groups, stratified by MIC.
  • Secondary outcomes: Daptomycin MIC distribution analysis and assessment of prior vancomycin exposure's impact on MICs.

Main Results:

  • Forty-six patients were included in the primary analysis; 60.9% were neutropenic.
  • Median TMC was 2 days for both standard and high daptomycin dose groups, with no significant difference between MIC subgroups (≤ 2 mg/L vs. >2 and ≤ 4 mg/L).
  • In the secondary analysis of 227 VRE isolates, 62% had daptomycin MICs of 3-4 mg/L, with similar prior vancomycin exposure across MIC groups.

Conclusions:

  • This retrospective review did not demonstrate a difference in TMC based on daptomycin dose or MIC for VRE bacteremia.
  • The study was not powered to detect differences in TMC, and limitations exist.
  • Prior vancomycin exposure did not appear to influence daptomycin MICs, and the observed frequency of higher MICs (3-4 mg/L) exceeds previously reported literature values.

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