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

ABSTRACT: The goal of this study was to genotypically characterize extended-spectrum ?-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 bla_CTX-M and bla_TEM 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.

SUBMITTER: Yasir M 

PROVIDER: S-EPMC6172265 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature