Newire, Enas Abdulsttar Mohamed Ali; (2018) Molecular Characterisation of MDR Klebsiella pneumoniae and Escherichia coli isolates from Egypt containing Transferable Resistance to β-Lactam Antibiotics. Doctoral thesis (Ph.D), UCL (University College London).

Text Newire EAMA 16 May 2018.pdf - Submitted Version Access restricted to UCL open access staff until 1 June 2024. Download (7MB)

Abstract

The significant increase in antimicrobial resistance (AMR) over the past few years is a serious global public health concern, particularly in the developing countries, where infections with resistant organisms are associated with poor clinical reporting and higher cost burdens. The objectives of this research were to characterise multidrug-resistant (MDR) Klebsiella pneumoniae and Escherichia coli isolates from Egypt and evaluate the bacterial fitness associated with the acquisition of transferable, plasmid-based, resistance to β-Lactam antibiotics. A total of 169 MDR Enterobacteriaceae isolates from nosocomial and community-acquired infections were collected from 10 different university teaching hospitals on two surveillance studies and were divided into three groups (group 1: 65 K. pneumoniae from 2000-2003, and group 2: 63 K. pneumoniae from 2009-2011), and (group 3: 41 E. coli from 2009-2011). Phenotypic tests were performed according to CLSI 2013. Genotypic characterisation of blaCTX-M-15, blaOXA-48, and blaVIM distribution were performed by PCR and sequence analysis. The distribution of class 1 and class 2 integrons, and repeat-spacer CRISPR-Cas systems were analysed. Selected resistance plasmids transferability, stability and fitness were evaluated. An increase in multidrug resistance and class 1 integrons over time in the K. pneumoniae isolates was observed. A high prevalence of multidrug resistance, and class 1 and class 2 integrons were observed among the E. coli isolates. Types I-E* and IV-B CRISPR-Cas were detected among the isolates, showing hypervariability, and an inverse correlation with AMR prevalence. The transfer of certain β-Lactam resistance plasmids revealed that positive epistasis plays an important role in stabilising resistance within the analysed transconjugants. The new insights reveal the potential for the stable accumulation of β-lactam resistance and other antibiotic resistances over time in bacterial cells and the lower tendency for losing those resistances even in the absence of antibiotic pressure.

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