Management of clinical infections of Escherichia coli by new β-lactam/ β-lactamase inhibitor combinations

Background and Objectives: Escherichia coli (E. coli) is an important member of Enterobacteriaceae family involved in severe infections. The increased rate of resistance towards different classes of antibiotics limits their treatment options. The aim of this study was to assess the in vitro activity of classical and novel combinations of β-lactam/ β-lactamase inhibitor against E. coli clinical isolates. Materials and Methods: 140 clinical isolates of E. coli were collected from clinical specimens from Gastrointestinal Surgery Center (GISC) in Egypt. Extended spectrum β-lactamase (ESBL) was detected by double disk synergy test. Furthermore, the minimum inhibitory concentrations (MICs) for five different combinations were determined using the broth microdilution method including: amoxicillin/clavulanate and ampicillin/sulbactam as an example for classical combinations and cefoperazone/sulbactam, ceftazidime/avibactam, and cefepime/enmetazobactam as an example for new combinations. Results: The percentage of ESBL production among the tested isolates was 46.4%. Isolates were highly resistant to classical β-lactam/ β-lactamase inhibitor combinations, where (40.7%) and (42.9%) of isolates were resistant to amoxicillin/clavulanate and ampicillin/sulbactam, respectively. While new β-lactam/ β-lactamase inhibitor combinations had promising inhibitory action. The addition of novel β-lactamase inhibitors restored the susceptibility of isolates, where (94.3%) of isolates became susceptible to ceftazidime/avibactam combination, followed by cefoperazone/sulbactam (89.2%) and cefepime/enmetazobactam (85.7%). The synergistic effect seems to be effective where ceftazidime and avibactam were synergistic in 80% of isolates. Conclusion: The antibacterial activity of some antimicrobial agents can be enhanced by the addition of new β-lactamase inhibitors. Further in vivo investigation is needed to confirm their therapeutic efficacy against local isolates.