Intravenous Amoxicillin-Sulbactam against Escherichia coli: Optimizing the Dose, Component Ratio and Infusion Time Using a Human Pharmacodynamic Model

AbstractAmoxicillin-sulbactam (AMX-SUL) is an aminopenicillin/β-lactamase inhibitor combination currently available in 29 countries which may be a suitable option for treating intra-abdominal infections. The aim of this study was to identify the optimal dose and ratio between components of this formulation through an ex-vivo human pharmacodynamic model against Escherichia Coli. Four volunteers were randomized to receive alternatively a single dose of AMX-SUL infused either over 30 min or 3h in the following ratios (g/g): 1/0.5; 1/1, 2/0.5 and 0/2. Time-kill studies were performed with the 0-, 0.5-, 2-, 4-, 6- and 8-h post-dosing sera against E. coli ATCC 25922 (AMX MIC, 2 μg/mL; AMX-SUL MIC, 2 μg/mL) and E. coli ATCC 35218 (AMX MIC, 1024 μg/mL; AMX-SUL MIC, 4-8 μg/mL). AMX-SUL 1g/0.5g infused over 30 min was only active at 0.5 h after dose, being inferior to both AMX-SUL 1g/1g and AMX-SUL 2g/0.5g against E. coli ATCC 25922, for which the 2h post-dose serum proved active. When tested against E. coli AtCC 3...