Impact of an Antimicrobial Stewardship Intervention on Within- and Between-Patient Daptomycin Resistance Evolution in Vancomycin-Resistant Enterococcus faecium

Antimicrob Agents Chemother. 2019 Mar 27;63(4):e01800-18. doi: 10.1128/AAC.01800-18. Print 2019 Apr.

Abstract

Vancomycin-resistant Enterococcus (VRE) is a leading cause of hospital-acquired infection, with limited treatment options. Resistance to one of the few remaining drugs, daptomycin, is a growing clinical problem and has previously been described in this hospital. In response to increasing resistance, an antimicrobial stewardship intervention was implemented to reduce hospital-wide use of daptomycin. To assess the impact of the intervention, daptomycin prescribing patterns and clinically reported culture results from vancomycin-resistant Enterococcus faecium (VREfm) bloodstream infections (BSIs) from 2011 through 2017 were retrospectively extracted and the impact of the intervention was estimated using interrupted time series analysis (ITS). We corrected for a change in MIC determination methodology by retesting 262 isolates using Etest and broth microdilution. Hospital-wide and within-patient resistance patterns of corrected daptomycin MICs are reported. Our data show that daptomycin prescriptions decreased from an average of 287 days of therapy/month preintervention to 151 days of therapy/month postintervention. Concurrently, the proportion of patients experiencing an increase in daptomycin MIC during an infection declined from 14.6% (7/48 patients) in 2014 to 1.9% (1/54 patients) in 2017. Hospital-wide resistance to daptomycin also decreased in the postintervention period, but this was not maintained. This study shows that an antimicrobial stewardship-guided intervention reduced daptomycin use and improved individual level outcomes but had only transient impact on the hospital-level trend.

Keywords: Enterococcus; antimicrobial resistance; antimicrobial stewardship; daptomycin; evolution.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimicrobial Stewardship / methods*
  • Antimicrobial Stewardship / statistics & numerical data
  • Bacteremia / drug therapy
  • Bacteremia / microbiology
  • Daptomycin / pharmacology*
  • Daptomycin / therapeutic use
  • Drug Resistance, Bacterial / drug effects*
  • Enterococcus faecium / drug effects*
  • Gram-Positive Bacterial Infections / drug therapy*
  • Gram-Positive Bacterial Infections / microbiology
  • Hospitals / statistics & numerical data
  • Hospitals / trends
  • Humans
  • Interrupted Time Series Analysis
  • Michigan
  • Retrospective Studies
  • Vancomycin-Resistant Enterococci / drug effects*

Substances

  • Daptomycin