1559. Ertapenem Plus Ceftriaxone or Ceftaroline Dual Β-Lactam Combination for Enterococcus faecalis

Abstract

BackgroundAmpicillin-ceftriaxone β-lactam therapy has become the standard of care for treating serious Enterococcus faecalis infections. Alternative regimens are of interest due to ceftriaxone’s association with C. difficile infections and VRE colonization, and ampicillin’s instability and inconvenient dosing schedule.Methods E. faecalis wild-type strain JH2-2 was utilized in a 48-hour in vitro pharmacodynamic model with a starting inoculum of 106 colony-forming units (CFU)/mL. Models were performed in duplicate to triplicate. Simulated doses of ertapenem 1g every 24 hours (fCmax 12.2 μg/mL; half-life 4 hours; MIC 4 μg/mL), ceftriaxone 2 g every 12 hours (fCmax 28.5 μg/mL; half-life 6.5 hours; MIC 512 μg/mL), and ceftaroline 600 mg every 8 hours (fCmax 27.1 μg/mL; half-life 2.7 hours; MIC 2 μg/mL) were tested. Ertapenem was also combined with ceftriaxone or ceftaroline. Bacterial counts were obtained at 0, 4, 8, 24, 32, and 48 hours. Bactericidal activity was defined as ≥ 3-log10 CFU/mL reduction from the initial inoculum. MICs were assessed at 0, 24, and 48 hours using E-tests in accordance with CLSI.ResultsErtapenem plus ceftriaxone, and ertapenem plus ceftaroline demonstrated bactericidal activity at 24 hours, but bacterial regrowth was observed at 48 hours (Table 1). An ertapenem MIC increase was only noted in one set of the ertapenem plus ceftriaxone models to 16mcg/mL at 48 hours, from 4mcg/mL at 0 hours. All other models did not have an increase in MIC.ConclusionBactericidal activity of ertapenem-based dual β-lactam combinations may prove to be an alternative treatment for severe E. faecalis infections. Mechanistic understanding of penicillin-binding protein (PBP) saturation and optimization of antimicrobial pharmacodynamics must be explored. Disclosures All authors: No reported disclosures.