Abstract

The rapid emergence of multiresistant microbial pathogens, dubbed superbugs, is a serious threat to human health. Extended spectrum beta lactamase (ESBL)-producing Escherichia coli is a superbug causing worldwide outbreaks, necessitating timely and accurate tracking of resistant strains. Accordingly, this study was designed to investigate the spread of ESBL-producing Escherichia coli isolates, to analyze the effect of different genotypic and phenotypic factors on in vitro resistance patterns, and to assess the diagnostic value of commonly used ESBL genetic markers. For that purpose, we cultured 250 clinical isolates and screened their susceptibility to beta-lactam antibiotics. Among 12 antibiotics screened, only imipenem seems to have remained resilient. We subsequently analyzed the ESBL phenotype of Escherichia coli isolates and examined potential associations between their resistance phenotypes and patient-related factors. ESBL genotyping of 198 multiresistant isolates indicated that 179 contained at least one blaCTX-M gene. As we statistically dissected the data, we found associations between overall resistance and body site / type of disease. Additionally, we confirmed the diagnostic value of testing both blaCTX-M-1 and blaCTX-M-15 in providing better prediction of overall resistance. Finally, on sequencing the amplification products of detected blaCTX-M genes, we discovered two novel variants, which we named blaCTX-M-14.2 and blaCTX-M-15.2.

Highlights

  • The emergence of antibiotic resistance is an increasingly alarming public health threat, since it undermines the efficacy of antibiotic treatment[1], and is expected to be the leading cause of global mortality by 2050, possibly exceeding cancer[2]

  • The study started by screening 250 clinical isolates recovered from different specimens for antibiotic-resistant Escherichia coli

  • Escherichia coli is a natural inhabitant of the mammalian intestine, but is recognized as one of the main causes of nosocomial, intestinal and extra-intestinal infections[12], and a leading cause of morbidity and mortality over the world

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Summary

Introduction

The emergence of antibiotic resistance is an increasingly alarming public health threat, since it undermines the efficacy of antibiotic treatment[1], and is expected to be the leading cause of global mortality by 2050, possibly exceeding cancer[2]. Resistance of enterobacteria to beta-lactam antibiotics is usually caused by intrinsic beta-lactamases that hydrolyze the beta-lactam ring of these antibiotic molecules This problem was initially solved by the introduction of extended spectrum cephalosporins as therapeutic agents in the mid-1980s. Resistance to beta-lactams is dramatically increasing in E. coli strains causing community-acquired infections, or health care-associated urinary tract and intra-abdominal infections. The proportion of such resistant strains exceeds 50% in developing countries likely because of the extensive and exaggerated clinical use of antibiotics[5]. ESBLs are believed to have originated from point mutations in the beta-lactamase (bla)-encoding genes belonging to the TEM and SHV types. The diversity of current CTX-M family members, though, is most likely due to subsequent mutations and recombination events[9]

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