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

Assessment of multidrug resistance in bacterial isolates from urinary tract-infected patients

“…The drugs they tested included Amikacin. Amikacin, Ceftazidime, Cefepime, Ciprofloxacin, Cefalotin, Cefoxitin, Ceftriaxone, Gentamycin, Imipenem, Meropenem, Tigecycline, Augmentin in as single and some other drugs in combination (Yasir et al, 2018). Current findings when compared with previous reports may give two conclusions.…”

“…Another reported the susceptibility of E. coli was Augmentin was 80%, Amikacin 60%, Piperacillin+Tazobactam was 90.66%, Ciprofloxacin 54.66% Ceftazidime and Ceftriaxone 33.33%, Cefotaxime 28%, Imipenem 100%, and Nitrofurantoin was 66.66% (Kumar, Singh, Ali, & Chander, 2014). A study in Saudi Arabia reported that 96.7% showed complete resistance to >5 antibiotics and moreover 16 isolates even to 10 tested the antibiotics showing dramatic multidrug resistance (Yasir et al, 2018). The drugs they tested included Amikacin.…”

<p>Treatment Failure in Urinary Tract Infections: A Warning Witness for Virulent Multi-Drug Resistant ESBL- Producing <em>Escherichia coli</em></p>

“…The rates and order of prevalence of β-lactamase genes were different in various studies from distinct and even similar regions, which could indicate their epidemiological diversity. 21,29,30 In the present study, all (100%) of the ESBL producers harbored cefotaximase (bla CTX-M ) gene. Confirming this result, all (100%) of the ESBL-producer isolates were resistant to cefotaxime.…”

“…Confirming this result, all (100%) of the ESBL-producer isolates were resistant to cefotaxime. Likewise, 100% of ESBL producers in a study from Bolivia, 27 99.5% of ESBL-positive E. coli in a study from western Saudi Arabia, 30 and 98.0% of ESBL-positive UPECs from community-acquired UTIs in the study from Turkey 25 were found to harbor the bla CTX-M gene. This revealed that the bla CTX-M type is the most frequent ESBL gene in different regions around the world.…”

Genetic Characterization Among Carbapenem-resistant Escherichia coli Strains Using Enterobacterial Repetitive Intergenic Consensus Polymerase Chain Reaction (ERIC-PCR) Fingerprinting in South Africa

“…In this study, STEC had the highest number of ERIC-PCR genotypes and our ndings are in contrary with the report by Moredo et al [73] where ETEC reportedly had the highest EPIC-PCR genotypes. Studies by Yasir et al [74] and Sun et al [75] reported the genetic diversities in multidrug resistant ESBLproducing E. coli although, our study did not screen for ESBL in the E. coli strains nevertheless provides an opportunity for further analysis. EPEC strains were predominantly isolated from river water samples and our study corroborates with another report by Khare et al [76].…”