Effective Oral Combination Treatment for Extended-Spectrum Beta-Lactamase-Producing Escherichia coli

Microb Drug Resist. 2019 Oct;25(8):1132-1141. doi: 10.1089/mdr.2019.0065. Epub 2019 May 20.


Background: Extended-spectrum beta-lactamase-producing Escherichia coli (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 in vitro and in vivo efficacy of a new combination of oral cephalosporins and amoxicillin/clavulanate in treatment of ESBL-EC. Methods: 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 in vitro using disk approximation and disk replacement methods. Combination treatment was assessed in vivo on 20 ESBL-EC urinary tract infection (UTI) patients. Results: 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 (p < 0.05). Addition of amoxicillin/clavulanate enhanced the susceptibility rate with cefixime from 8.6% to 86.3%, significantly higher than with other cephalosporins (p < 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 in vitro synergy test and complete clinical and microbiological resolution after completion of cefixime and amoxicillin/clavulanate oral treatment course. Conclusions: Cefixime and amoxicillin/clavulanate combination therapy could be an effective oral outpatient treatment option for ESBL-EC. In vitro synergistic testing is simple and predictive of successful treatment.

Keywords: E. coli; cefixime; clavulanic acid; extended-spectrum beta-lactamase (ESBL); synergy.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amoxicillin-Potassium Clavulanate Combination / therapeutic use*
  • Anti-Bacterial Agents / therapeutic use*
  • Cefixime / therapeutic use
  • Cefotaxime / therapeutic use
  • Cephalosporins / therapeutic use
  • Escherichia coli / drug effects*
  • Escherichia coli / metabolism
  • Escherichia coli Infections / drug therapy*
  • Escherichia coli Infections / metabolism
  • Escherichia coli Infections / microbiology
  • Female
  • Humans
  • Male
  • Microbial Sensitivity Tests / methods
  • Middle Aged
  • Urinary Tract Infections / drug therapy
  • Urinary Tract Infections / microbiology
  • Young Adult
  • beta-Lactamases / metabolism*


  • Anti-Bacterial Agents
  • Cephalosporins
  • Amoxicillin-Potassium Clavulanate Combination
  • Cefixime
  • beta-Lactamases
  • Cefotaxime