Impact of an antimicrobial stewardship intervention on within and between patient daptomycin resistance evolution in vancomycin-resistant Enterococcus faecium.

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 VRE faecium blood stream infections (BSI) from 2011 through 2017 were retrospectively extracted and the impact of the intervention was estimated using interrupted time series analysis. We corrected for a change in MIC testing methodology by retesting 262 isolates using E-test 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 pre-intervention, to 151 days of therapy/month post-intervention. Concurrently, the proportion of patients experiencing an increase in daptomycin minimum inhibitory concentration (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 post-intervention 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.