Multicenter study of high-dose daptomycin for treatment of enterococcal infections

Abstract

Enterococci are among the leading pathogens isolated in hospital-acquired infections. Current antimicrobial options for vancomycin-resistant enterococci (VRE) are limited. Prior data suggest that daptomycin at >6 mg/kg of body weight/day may be used to treat enterococcal infections. We retrospectively evaluated the effectiveness and safety of high-dose daptomycin (HD-daptomycin) therapy (>6 mg/kg) in a multicenter cohort of adult patients with enterococcal infections to describe the characteristics and outcomes. Two hundred forty-five patients were evaluated. Enterococcus faecium was identified in 175 (71%), followed by Enterococcus faecalis in 49 (20%) and Enterococcus spp. in 21 (9%); overall, 204 (83%) isolates were VRE. Enterococcal infections included bacteremia (173, 71%) and intra-abdominal (35, 14%) and bone and joint (25, 10%) infections. The median dosage and duration of HD-daptomycin were 8.2 mg/kg/day (interquartile range [IQR], 7.7 to 9.7) and 10 days (IQR, 6 to 15), respectively. The overall clinical success rate was 89% (193/218), and microbiological eradication was observed in 93% (177/191) of patients. The median time to clearance of blood cultures on HD-daptomycin was 3 days (IQR, 2 to 5). The 30-day all-cause mortality rate was 27%, and 5 (2%) patients developed daptomycin-nonsusceptible enterococcal strains while on HD-daptomycin. Seven patients (3%) had creatine phosphokinase (CPK) elevation, yet no HD-daptomycin regimen was discontinued due to an elevated CPK and all patients were asymptomatic. Overall, there was a high frequency of clinical success and microbiological eradication in patients treated with HD-daptomycin for enterococcal infections, even in patients with complicated and difficult-to-treat infections. No adverse event-related discontinuation of HD-daptomycin was noted. HD-daptomycin may be an option for the treatment of enterococcal infections.

Fig 1

Clinical outcome proportion per enterococcal species. Individual percentage of clinical success component is reported within the stacked bars per enterococcal species. The frequency of clinical success for E. faecium, E. faecalis, and Enterococcus spp. were 85.6%, 95.7%, and 94.7%, respectively.

Fig 2

Clinical success stratified by daptomycin (DAP) MIC. The individual percentages of the clinical success component are reported within the stacked bars per daptomycin MIC. The frequencies of clinical success for daptomycin MICs of 0.25, 0.38, 0.5, 1.0, 1.5, 2, 3, 4, and 8 mg/liter were 100%, 100%, 100%, 93%, 85%, 84%, 91%, 81%, and 0%, respectively.

Fig 3

Box-and-whisker plot of maximum observed creatine phosphokinase level after 3 doses to 3 days of high-dose daptomycin (HD DAP) Circles indicate outliers and asterisks indicate extreme values.