Date of Award

4-2016

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Medical Education

First Advisor

Tibor Pal MD, PhD

Second Advisor

Mariam AI Shamsi, PhD

Third Advisor

Farah Mustafa, PhD

Abstract

The emergence and rapid spread of multi-drug resistant (MDR) Enterobacteriaceae is one of the most challenging problems we currently faced. However, locally, no details on the strains causing outbreaks are available. Furthermore, globally, we still do not understand what makes certain clones capable of spreading widely while others are only confined to sporadic cases. Aim: Our aim was to characterize the virulence factors, antibiotic and disinfectant susceptibilities of local clonal and sporadic Escherichia coli and Klebsiella pneumoniae strains and to analyze the data to reveal which particular feature might be responsible for the outbreak potential of clonal isolates. Methods: Escherichia coli and Klebsiella pneumoniae strains collected from countries of the Arabian Peninsula were subjected to genotyping by PCR targeting a broad spectrum of virulence and antibiotic resistance genes. This was followed by antibiotic susceptibility tests, serum resistance and biofilm formation assays and molecular typing by macro-restriction analysis and multilocus sequence typing. Results: Our study shows that among blood stream E. coli isolates, the rate of strains expressing R4 core type is currently much higher than seen before, most likely due to a few multi-resistant clones that have emerged recently. Further studies should reveal whether, beyond their more extensive antimicrobial resistance, the presence of the previously rare core types, or possibly the lower base-line immunity in the population against them, contributes to their recent epidemiological success. We also show that a majority of local K. pneumoniae clones do not possess considerably more virulence related features than sporadic isolates. Rather, they are clearly distinguishable from the latter group by their broader spectrum of resistance to non-ß-lactam antibiotics, well substantiated by the increased carriage of the respective resistance genes. Resistance to disinfectants was observed to be more common among K. pneumoniae strains non-susceptible to carbapenems than among the antibiotic sensitive isolates. We speculate that this may also increase the outbreak potential of the strains. Finally, we show that a considerable part of local carbapenem resistant K. pneumoniae strains are still susceptible to fosfomycin, although the rate of resistance to fosfomycin, particularly among blood stream isolates, is already alarming. Conclusions: Together, data reveals that it is particularly the increased resistance rather than any specific virulence-related feature that makes strains spread as clones. A well-organized surveillance system based on molecular typing is needed in the country to follow the characteristics of the spread of multidrug resistance organisms in the region.

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