Examining the Combination of Cefixime and Amoxicillin/Clavulanate against Extended-Spectrum Beta-Lactamase-Producing <b><i>Escherichia coli</i></b> Isolates

Abstract

<b><i>Introduction:</i></b> Community-acquired urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing <i>Escherichia coli</i> have limited oral therapeutic options and pose significant clinical challenges. The goal of this study was to evaluate the in vitro synergy between CFM and AMC against ESBL <i>E. coli</i> with aims to identify an oral treatment option for UTIs. <b><i>Methods:</i></b> Minimum inhibitory concentrations (MICs) of CFM in the presence of AMC were determined for 46 clinical isolates by placing a CFM Etest on a plate with AMC impregnated in the agar. Isolates with CFM MIC ≤1 μg/mL in the presence of AMC were considered susceptible to the CFM and AMC combination. Five isolates were then selected for further testing using time-kill analysis in the presence of CFM, AMC, and CFM with AMC. Time-kill curves were plotted to determine synergy over 24 h. <b><i>Results:</i></b> AMC improved the activity of CFM against ESBL <i>E. coli</i> isolates by 128-fold in the Etest analysis with 85% of tested isolates being susceptible to the combination. A fourfold or greater reduction in CFM MIC was exhibited in 44 of 46 (96%) isolates when in the presence of AMC. Synergy and bactericidal activity between CFM and AMC were exhibited in each of the five isolates tested by time-kill analysis. <b><i>Discussion/Conclusion:</i></b> This study found that AMC improves the activity of CFM against ESBL <i>E. coli</i> and that this antibiotic combination has potential as an oral therapeutic option to treat ESBL <i>E. coli</i> UTIs.