Pharmacodynamics of Daptomycin Against Enterococcus faecium and Enterococcus faecalis in the Murine Thigh Infection Model.

Pharmacodynamics of Daptomycin Against Enterococcus faecium and Enterococcus faecalis in the Murine Thigh Infection Model. Antimicrob Agents Chemother. 2018 Jul 16;: Authors: Kidd JM, Abdelraouf K, Asempa TE, Humphries RM, Nicolau DP Abstract The Clinical Laboratory Standards Institute (CLSI) daptomycin MIC susceptibility breakpoint for the treatment of enterococcal infections is ≤4 μg/mL. However, patients receiving daptomycin for enterococci with MICs ≤4 μg/mL may experience treatment failures. We assessed the pharmacodynamics of daptomycin against enterococci in a neutropenic murine thigh infection model and determined exposures necessary for bacteriostasis and 1 log10 CFU reduction against Enterococcus faecalis and Enterococcus faecium We further characterized daptomycin efficacy at clinically achievable exposures.Six E. faecium and 6 E. faecalis isolates (daptomycin MIC, 0.5-32 μg/mL) were studied. Daptomycin was administered at various doses over 24 h to achieve area under the free drug concentration-time curve to MIC ratios (fAUC0-24/MIC) from 1-148. Daptomycin regimens that simulate mean human exposures following doses of 6, 8, and 10 mg/kg/d were also studied. Efficacy was assessed by differences in log10 CFU/thigh at 24 h. The Hill equation was used to estimate fAUC0-24/MIC required to achieve bacteriostasis and 1 log10 CFU reduction.For E. faecium, 1 log10 CFU reduction required a fAUC0-24/MIC of 12.9 (R2=0.71). For...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research