Effective Oral Combination Treatment for Extended-Spectrum Beta-Lactamase-Producing <i>Escherichia coli</i>

Abstract

<b><i>Background:</i></b> Extended-spectrum beta-lactamase-producing <i>Escherichia coli</i> (ESBL-EC) is increasing worldwide. The drugs of choice for treatment of ESBLs are parenteral carbapenems. The aim of this study was to evaluate the <i>in vitro</i> and <i>in vivo</i> efficacy of a new combination of oral cephalosporins and amoxicillin/clavulanate in treatment of ESBL-EC. <b><i>Methods:</i></b> A total of 150 ESBL-EC samples were collected over 1 year from two referral centers. Synergistic studies of cephalosporins and amoxicillin/clavulanate were performed <i>in vitro</i> using disk approximation and disk replacement methods. Combination treatment was assessed <i>in vivo</i> on 20 ESBL-EC urinary tract infection (UTI) patients. <b><i>Results:</i></b> ESBL-EC isolates were confirmed in 150 patients with a mean age of 46.67 years, 75.2% of them being women. Antibiotic susceptibility testing of isolates indicated high resistance rate to oral antibiotics. The frequency of positive synergy and mean distance of synergy between cephalosporins and amoxicillin/clavulanate was significantly higher with cefotaxime and cefixime compared with cefpodoxime, cefdinir, and ceftazidime using disk approximation and disk replacement methods (<i>p</i> < 0.05). Addition of amoxicillin/clavulanate enhanced the susceptibility rate with cefixime from 8.6% to 86.3%, significantly higher than with other cephalosporins (<i>p</i> < 0.0005). Cefixime and amoxicillin/clavulanate synergy was not affected by age, gender, hospital, department, sample type, or bacterial load. Eighteen of 20 ESBL-EC-positive UTI patients had a positive <i>in vitro</i> synergy test and complete clinical and microbiological resolution after completion of cefixime and amoxicillin/clavulanate oral treatment course. <b><i>Conclusions:</i></b> Cefixime and amoxicillin/clavulanate combination therapy could be an effective oral outpatient treatment option for ESBL-EC. <i>In vitro</i> synergistic testing is simple and predictive of successful treatment.