Nour Yahfoufi

Date of Award

2-2014

Document Type

Thesis

Degree Name

Master of Science in Medical Sciences (MSMS)

Department

Medical Microbiology and Immunology

First Advisor

Tibor Pal MD, PhD

Second Advisor

Bassam Ali PhD

Third Advisor

Agnes Sonnevend MD, PhD

Abstract

The emergence and global spread of carbapenem resistant Enterobacteriaceae is alarming world-wide phenomenon that also affects the Middle East due to limited treatment options for such infections and their common association with high level of fatality. The most important mechanism of such resistance is caused by the production of various carbapenemase enzymes. In the Arabian Peninsula, so far, NDM and OXA48-like carbapenemases have been reported, while elsewhere other enzymes, e.g. VIM, IMP and KPC are also commonly found. Our aim was to systematically look for the VIM-type carbapenemases among local isolates and to characterize their genetic background.

Initially, screening isolates from Abu Dhabi hospitals, we identified a single Enterobacter cloaceae strain carrying the VIM-4 allele. This was the first such isolate ever reported from the peninsula. Subsequently, investigating isolates from Kuwait, Saudi Arabia, Oman and the UAE, we identified a further 11 isolates, one E. cloaceae from Saudi Arabia, two from Oman, one from Kuwait and also one Escherichia coli from this country. Besides these, the latter country also provided six Klebsiella pneumonia isolates. All strains produiced the VIM-4 variant of the enzyme as determined by the sequencing of their genes. In all cases, the gene was located on plasmids of varying sizes, either non-typable or belonging to the IncA/C group; most of them were conjugative and they commonly harbored other Β-lactamase genes, such as CTX-M or CMY-4. In all strains the VIM-4 gene was located within a class I integrin – with some variations between the gene casettes present – similar to strains previously identified in North Africa and Italy, suggesting the possibility of spread. Clonal typing revealed that the relatively high incidence of VIM-producer Enterobacteriaceae encountered in Kuwait was not due to the spread of a particular clone, but most probably was the result of the transfer of an IncA/C plasmid, co-harboring blaVIM-4 and blaCMY-4, into Klebsiella pneumonia and E. coli.

Our data show that, beyond NDM and OXA-48-like, VIM type carbapenemases are the third most common isolates in the Arabian Peninsula. Further investigation is needed to monitor the spread of clones and genes in the region.

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