High-dose daptomycin for the treatment of invasive infections due to <i>Enterococcus faecalis</i> isolates with intermediate susceptibility

BACKGROUND: Enterococcus faecalis isolates with a daptomycin minimum inhibitory concentration (MIC) of 4 mg/L are classified as intermediate by the Clinical and Laboratory Standards Institute (CLSI). There is limited evidence to guide the use of high-dose daptomycin for these infections when alternative therapy options cannot be used. OBJECTIVES: To determine the rate of clinical failure of E. faecalis invasive infections with a daptomycin MIC of 4 mg/L treated with high-dose daptomycin or best alternative therapy (BAT). METHODS: This was a single-centre, retrospective, observational, cross-sectional study that compared high-dose daptomycin to BAT for invasive E. faecalis infections. High-dose daptomycin was defined as ≥8 mg/kg/dose. The primary outcome was clinical failure, a composite endpoint including switch from definitive to alternative therapy secondary to clinical decline, infection-related hospital readmission while on definitive treatment for the index infection, or infection-related mortality within 30 days of definitive therapy completion. High-dose daptomycin versus BAT groups were matched and compared in a 1:3 ratio based on initial source of the positive E. faecalis isolate. RESULTS: Of 112 patients included, 28 patients received daptomycin and 84 received BAT. There was no difference in the primary outcome of clinical failure between the daptomycin and BAT groups (7% versus 5%, P = 0.64). All-cause mortality was similar between the daptomycin and BAT groups (11% versus 10%, P = 1.00). CONCLUSIONS: There was no difference observed in clinical failure rates between patients treated with high-dose daptomycin versus BAT. All-cause mortality was also similar between the groups. Further studies are needed to confirm these findings in high-burden E. faecalis infections with intermediate daptomycin susceptibility.