Daptomycin in the treatment of enterococcal bloodstream infections and endocarditis: a EUCAST position paper

This position paper describes the view adopted by EUCAST on the role of daptomycin in the treatment of serious infections caused by Enterococcus species.

High-dose daptomycin is considered effective in the treatment of enterococcal bloodstream infection (BSI) and endocarditis, although published clinical experience with the latter condition is limited.

EUCAST reviewed the available published data on pharmacokinetics-pharmacodynamics (PK-PD), resistance selection, clinical efficacy and safety for the use of 10-12 mg/kg/day of daptomycin for these conditions, noting that the doses licensed by the European Medicines Agency are only 4-6 mg/kg/day, and only for infections caused by Staphylococcus aureus.

The PK-PD evidence shows that, even with doses of 10-12 mg/kg/day, it is not possible to treat infections caused by isolates at the upper end of the wild-type distributions of Enterococcus faecalis (with MICs of 4 mg/L) and E. faecium (with MICs of 4 or 8 mg/L). For this reason, and because there are ongoing issues with the reliability of laboratory testing, EUCAST lists daptomycin breakpoints for Enterococcus species as "IE"-insufficient evidence. EUCAST advises increased vigilance in the use of high-dose of daptomycin to treat enterococcal BSI and endocarditis. Additional PK-PD studies and prospective efficacy and safety studies of serious Enterococcal infections treated with high-dose daptomycin may permit the setting of breakpoints in the future.