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Sci Rep. 2018 Oct 4;8(1):14847. doi: 10.1038/s41598-018-33093-8.

Molecular characterization, antimicrobial resistance and clinico-bioinformatics approaches to address the problem of extended-spectrum β-lactamase-producing Escherichia coli in western Saudi Arabia.

Author information

1
Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia. yasirkhattak.mrl@gmail.com.
2
Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
3
Biology Department, Faculty of Science, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.
4
Center of Innovation in Personalized Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
5
Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.
6
Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
7
Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
8
Clinical and molecular microbiology laboratories King Abdulaziz University Hospital, Jeddah, Saudi Arabia.
9
Infection Control & Environmental Health Unit, King Abdulaziz University Hospital, King Abdulaziz University, Jeddah, Saudi Arabia.
10
Department of Public Health, Faculty of Nursing, King Abdulaziz University, Jeddah, Saudi Arabia.

Abstract

The goal of this study was to genotypically characterize extended-spectrum β-lactamase-producing Escherichia coli isolates from the western region of Saudi Arabia and to identify active antibiotics against these isolates using phenotypic and molecular modeling. In total, 211 ESBL-producing E. coli isolates recovered from heterogeneous clinical specimens were identified by MALDI-TOF. Thirty-two sequence types (STs) were identified from a multilocus sequence typing (MLST) analysis of ESBL-producing E. coli, including a novel ST (ST8162). The most common ST in the Saudi and expatriate population was ST131, followed by ST38. All the isolates were multidrug resistant (MDR), and >95% of the isolates were resistant to third-generation (ceftriaxone and ceftazidime) and fourth-generation (cefepime) cephalosporins. The ESBL-positive E. coli isolates primarily harbored the blaCTX-M and blaTEM genes. No resistance was observed against the carbapenem antibiotic group. All the ESBL-producing E. coli isolates were observed to be susceptible to a ceftazidime/avibactam combination. Molecular interaction analyses of the docked complexes revealed the amino acid residues crucial for the binding of antibiotics and inhibitors to the modeled CTX-M-15 enzyme. Importantly, avibactam displayed the most robust interaction with CTX-M-15 among the tested inhibitors in the docked state (∆G = -6.6 kcal/mol). The binding free energy values for clavulanate, tazobactam and sulbactam were determined to be -5.7, -5.9 and -5.2 kcal/mol, respectively. Overall, the study concludes that 'ceftazidime along with avibactam' should be carefully used as a treatment option against only carbapenem-resistant MDR ESBL-producing E. coli in this region.

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