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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.