Examining the Combination of Cefixime and Amoxicillin/Clavulanate against Extended-Spectrum Beta-Lactamase-Producing Escherichia coli Isolates. 2022

Haedi Thelen, and Thomas J Dilworth, and Renée-Claude Mercier
Department of Pharmacy Practice and Administrative Sciences, University of New Mexico College of Pharmacy, Albuquerque, New Mexico, USA.

BACKGROUND Community-acquired urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli 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 E. coli with aims to identify an oral treatment option for UTIs. METHODS 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. RESULTS AMC improved the activity of CFM against ESBL E. coli 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. CONCLUSIONS This study found that AMC improves the activity of CFM against ESBL E. coli and that this antibiotic combination has potential as an oral therapeutic option to treat ESBL E. coli UTIs.

UI MeSH Term Description Entries
D008826 Microbial Sensitivity Tests Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses). Bacterial Sensitivity Tests,Drug Sensitivity Assay, Microbial,Minimum Inhibitory Concentration,Antibacterial Susceptibility Breakpoint Determination,Antibiogram,Antimicrobial Susceptibility Breakpoint Determination,Bacterial Sensitivity Test,Breakpoint Determination, Antibacterial Susceptibility,Breakpoint Determination, Antimicrobial Susceptibility,Fungal Drug Sensitivity Tests,Fungus Drug Sensitivity Tests,Sensitivity Test, Bacterial,Sensitivity Tests, Bacterial,Test, Bacterial Sensitivity,Tests, Bacterial Sensitivity,Viral Drug Sensitivity Tests,Virus Drug Sensitivity Tests,Antibiograms,Concentration, Minimum Inhibitory,Concentrations, Minimum Inhibitory,Inhibitory Concentration, Minimum,Inhibitory Concentrations, Minimum,Microbial Sensitivity Test,Minimum Inhibitory Concentrations,Sensitivity Test, Microbial,Sensitivity Tests, Microbial,Test, Microbial Sensitivity,Tests, Microbial Sensitivity
D004926 Escherichia coli A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc. Alkalescens-Dispar Group,Bacillus coli,Bacterium coli,Bacterium coli commune,Diffusely Adherent Escherichia coli,E coli,EAggEC,Enteroaggregative Escherichia coli,Enterococcus coli,Diffusely Adherent E. coli,Enteroaggregative E. coli,Enteroinvasive E. coli,Enteroinvasive Escherichia coli
D004927 Escherichia coli Infections Infections with bacteria of the species ESCHERICHIA COLI. E coli Infections,E. coli Infection,Infections, E coli,Infections, Escherichia coli,E coli Infection,E. coli Infections,Escherichia coli Infection,Infection, E coli,Infection, E. coli,Infection, Escherichia coli
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001618 beta-Lactamases Enzymes found in many bacteria which catalyze the hydrolysis of the amide bond in the beta-lactam ring. Well known antibiotics destroyed by these enzymes are penicillins and cephalosporins. beta-Lactamase,beta Lactamase,beta Lactamases
D014552 Urinary Tract Infections Inflammatory responses of the epithelium of the URINARY TRACT to microbial invasions. They are often bacterial infections with associated BACTERIURIA and PYURIA. Infection, Urinary Tract,Infections, Urinary Tract,Tract Infection, Urinary,Tract Infections, Urinary,Urinary Tract Infection
D019980 Amoxicillin-Potassium Clavulanate Combination A fixed-ratio combination of amoxicillin trihydrate and potassium clavulanate. Amoxicillin-Clavulanic Acid,Potassium Clavulanate-Amoxicillin Combination,Amox-clav,Amoxi-Clavulanate,Amoxycillin-Clavulanic Acid,Augmentin,BRL-25000,Clavulanate Potentiated Amoxycillin,Clavulin,Co-amoxiclav,Coamoxiclav,Spektramox,Synulox,Amox clav,Amoxi Clavulanate,Amoxicillin Clavulanic Acid,Amoxicillin Potassium Clavulanate Combination,Amoxycillin Clavulanic Acid,Amoxycillin, Clavulanate Potentiated,BRL 25000,BRL25000,Co amoxiclav,Potassium Clavulanate Amoxicillin Combination
D020682 Cefixime A third-generation cephalosporin antibiotic that is stable to hydrolysis by beta-lactamases. Cefixime Anhydrous,Cefixime Trihydrate,FK 027,FK-027,FR-17027,Suprax,FK027,FR 17027,FR17027

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