To establish the role of local transmission versus possible pathogen import due to previous foreign exposure in infections caused by carbapenem non-susceptible Enterobacteriaceae in the Arabian Peninsula, 200 independent isolates collected in 16 hospitals of Saudi Arabia, Kuwait, Oman and the United Arab Emirates were studied. All strains were multidrug resistant; 42.5% of them also qualified as extremely drug resistant. The frequency of various carbapenemases varied according to the participating countries, but in the collection, as a whole, bla NDM-1 was the most frequently encountered carbapenemase gene (46.5%) followed by bla OXA-48-like gene (32.5%). A comparatively high rate (8.9%) of multi-clonal strains carrying both bla NDM and bla OXA-48-like genes in the United Arab Emirates, representing the most resistant subgroup, was encountered. No KPC-expressing isolates were detected. Three major clones of bla NDM-1 carrying Klebsiella pneumoniae of ST152 (n = 22, Saudi Arabia), ST14 (n = 7, United Arab Emirates) and ST147 types (n = 9, Oman) were identified, the latter two clones carrying similar, but not identical HI1b incompatibility type plasmids of >170kb. While from 78.6% of the cases with documented foreign hospitalization bla NDM positive strains were isolated, these strains formed only 25.6% of all the isolates expressing this enzyme. In fact, 56.8% of the NDM, 75.7% of OXA-48-like and 90.9% of VIM positive strains were recovered from patients without documented foreign exposure, neither in the form of travel or prior hospitalization abroad, suggesting a high rate of autochthonous infections. This, considering the extensive links of these countries to the rest of the world, predicts that trends in the local epidemiology of carbapenem resistant strains may increasingly affect the spread of these pathogens on the global scale. These results call for improved surveillance of carbapenem resistant Enterobacteriaceae in the countries of the Arabian Peninsula.

Among 28 clinically relevant, carbapenem non-susceptible Enterobacteriaceae isolates collected in 2009-2011 in the United Arab Emirates three Klebsiella pneumoniae, two Escherichia coli, one Enterobacter cloacae and one Citrobacter freundi were identified to produce NDM-1 carbapenemase. Unexpectedly, with the exception of a K. pneumoniae strain, sequence type ST11, originally acquired in India and subsequently spread nosocomially in the UAE, the majority of the strains could not be directly linked to foreign travel. All isolates harboured the bla NDM-1 gene on plasmids of IncA/C, IncHI1b and IncX3 types, or were untypable. IncX3 type plasmids with a mass of 50 kb and with the same or highly similar restriction patterns, with regions flanking the bla NDM-1 gene identical to the IncX3 NDM plasmids described from China were present in three different species, Enterobacter cloacae, Escherichia coli and C. freundii. Our findings strongly support the assumptions that, beyond the Indian subcontinent, the Middle East is an important reservoir of NDM-producing organisms. Furthermore, we also provide evidence that IncX3 plasmids, recently implicated in the spread of bla NDM-1 in China, have been widely distributed and are important vehicles of the inter-species spread of the NDM-1 gene.

This is the first report on the presence of the plasmid-coded mcr-1 gene in a variety of multi-resistant clinical isolates from the Arabian Peninsula indicating that several commonly used antibiotics can potentially facilitate the spread of mcr-1 carrying strains, or directly, mcr-1 containing plasmids.

The emergence of pan-resistant Klebsiella pneumoniae strains is an increasing concern. In the present study, we describe a cluster of 9 pan-resistant K. pneumoniae sequence type 147 (ST147) isolates encountered in 4 patients over nearly 1 year in 3 hospitals of the United Arab Emirates (UAE). The isolates exhibited highly similar genotypes. All produced chromosomally encoded OXA-181, and the majority also produced the NDM-5 carbapenemase. As with the previously described single isolate from the UAE, MS6671, the mgrB was disrupted by a functional, ISEcp1-driven bla OXA-181 insertion causing resistance to carbapenems. The mutation was successfully complemented with an intact mgrB gene, indicating that it was responsible for colistin resistance. bla NDM-5 was located within a resistance island of an approximately 100-kb IncFII plasmid carrying ermB, mph(A), bla TEM-1B , rmtB, bla NDM-5 , sul1, aadA2, and dfrA12 resistance genes. Sequencing this plasmid (pABC143-NDM) revealed that its backbone was nearly identical to that of plasmid pMS6671E from which several resistance genes, including bla NDM-5 , had been deleted. More extensive similarities of the backbone and the resistance island were found between pABC143C-NDM and the bla NDM-5 -carrying IncFII plasmids of two K. pneumoniae ST147 isolates from South Korea, one of which was colistin resistant, and both also produced OXA-181. Notably, one of these strains was isolated from a patient transferred from the UAE. Our data show that this pan-resistant clone has an alarming capacity to maintain itself over an extended period of time and is even likely to be transmitted internationally.

Screening 155 carbapenem non-susceptible Acinetobacter baumannii strains recovered in Abu Dhabi hospitals identified two metallo-ß-lactamase bla(NDM) gene-carrying isolates. They were isolated 4 months apart from the urine of a cancer patient previously treated in Egypt, Lebanon and in the United Arab Emirates. They were clonally related and carried the bla(NDM-2) gene recently identified in A. baumannii in Egypt and Israel. Sequences surrounding the bla(NDM-2) gene showed significant similarities with those associated with bla(NDM-1) in Enterobacteriaceae and A. baumannii. Repeated isolation of bla(NDM-2)-positive A. baumannii in the Middle East raises the possibility of the local emergence and spread of a unique clone.