Impact of Daptomycin Minimum Inhibitory Concentration on Clinical Cure Rates for Vancomycin-Resistant Enterococcus Infections

Abstract

Purpose Vancomycin-resistant Enterococcus (VRE) infections are designated a serious threat. Recently, the Clinical and Laboratory Standards Institute revised daptomycin breakpoints for Enterococcus faecium infections to reflect a minimum inhibitory concentration (MIC) of less than 4 mg/L as susceptible dose dependent and 8 mg/L or greater as resistant. The objective was to compare clinical outcomes for patients who had a VRE bloodstream infection (BSI) and a daptomycin MIC of 2 mg/L or greater (low MIC group) versus a daptomycin MIC of 3 to 4 mg/L (high MIC group). Methods This was a single-center, retrospective study of adult patients receiving 48 hours or more of daptomycin therapy. The following primary and secondary outcomes were assessed: microbiological cure, clinical cure, and 30-day all-cause mortality. Results Sixty-five patients were included in this analysis: 16 patients in the low MIC group and 49 in the high MIC group. Patients in the high MIC group received a longer duration of therapy (14.0 vs 7.5 days, P = 0.047), had a larger percentage of patients receiving concomitant antimicrobials (85.7% vs. 56.2%, P = 0.013), and were more likely to be infected with E. faecium (98.0% vs 56.2%, P < 0.001) compared with the low MIC group. Patients in the low MIC group had a significantly higher clinical cure rate (69.0% vs 31.0%, P = 0.009), microbiological cure rate (100.0% vs. 73.0%, P = 0.027), and a comparable 30-day all-cause mortality rate (19.0% vs 41.0%, P = 0.139) compared with the high MIC group. Conclusions High daptomycin MICs were associated with worse outcomes in our patient cohort with VRE BSIs.