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Amna Eissa Al Baloushi

Department of Medical Microbiology and Immunology

College of Medicine and Health Sciences

Dissertation

Title

Characterization of carbapenemase producer Enterobacteriaceae isolated in the United

Arab Emirates

Faculty Advisor

Dr. Agnes Sonnevend-Pál

Defense Date

22 June 2015

Abstract

Theefficient control of the spreadof carbapenemaseproducer Enterobacteriaceae, amajor public health threat world-

wide, requires knowledge on the molecular epidemiology and genetic background of the emerging carbapenemase

genes. Our aim was to investigate the genetic support of New-Delhi metallo-beta-lactamase and OXA-48-type

carbapenemase genes in carbapenem resistant Enterobacteriaceae isolated in the United Arab Emirates. The first

seven NDM-producer Enterobacteriaceae, collected during 2009-2011 in the UAE and subsequently five NDM and

OXA-48-type carbapenemase co-producer Klebsiella pneumoniae isolated during 2011-2013 in three hospitals of the

Emirates, were characterized. Strains’ clonality and the transmissibility of carbapenemase genes were assessed. The

genetic support of carbapenemases was studied by characterization of plasmids and by sequencing the genes’

surrounding. All isolates harbored the blaNDM-1 gene on conjugative plasmids. Furthermore, IncX3 plasmids with

almost identical restriction patterns were present in Enterobacter cloacae, Escherichia coli and Citrobacter freundii.

The NDM plasmid of one K. pneumoniae, harboring blaOXA-48 also, was almost identical to these IncX3 plasmis.

Three of the five double carbapenemase producer ST14 K. pneumoniae possessing blaNDM-1 and blaOXA-232 were

clonally related. The fifth, unrelated K. pneumoniae co-produced NDM-1 and OXA-162. These findings proved that

IncX3 plasmids play an important role in the inter-species spread of the blaNDM gene, and also that the emergence

of NDM- and OXA-48-type carbapenemase co-producer K. pneumoniae is partially a clonal phenomenon in the UAE.

Since the carbapenemase producer Enterobacteriaceae are extremely drug resistant, leaving few treatment options,

the efficacy of alternative antimicrobials was also assessed by testing the effect of the himenochirin-1B analogue

antimicrobial peptide on selected strains and the fosfomycin susceptibility of 45 carbapenem non-susceptible

Escherichia coli isolates. The [E6k,D9k]hymenochirin-1B showed high potency against all selected NDM-producer.

Furthermore, fosfomycin could be a valuable therapeutic option against carbapenem-resistant E. coli, since the

susceptibility of all isolates tested was retained.

Research Relevance and Potential Impact

Ms. Baloushi’s research set the UAE’s experience with carbapenem resistant Enterobacteriaceae, into a global context. The molecular investigation

of multi-drug resistant organisms highlighted the mode of spreading of these bacteria. Furthermore, she proved that fosfomycin could be a useful

option for the treatment of carbapenem resistant Escherichia coli infections.

May 31, 2016
Dec 13, 2017
Nov 22, 2022