Multihospital Occurrence of Pan-Resistant Klebsiella pneumoniae Sequence Type 147 with an IS Ecp1-Directed blaOXA-181 Insertion in the mgrB Gene in the United Arab Emirates

Abstract

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.

Keywords: Klebsiella pneumoniae; carbapenems; colistin; pan-resistance.

FIG 1

Comparative typing of members of the cluster. (A) rep-PCR (DiversiLab); (B) PFGE.

FIG 2

Hybridization of the genomic DNA fragments of strains with an OXA-181 probe. Samples: 1 and 11, Salmonella enterica serovar Braenderup strain H9812, molecular mass standard; 2, ABC143A; 3, ABC143B; 4, ABC143C; 5, ABC143D; 6, ABC143E; 7, ABC143F; 8, ABC146; 9, ABC164; 10, MS6671.

FIG 3

Structure of the mgrB::bla_OXA-181 insert.

FIG 4

Structure of pABC143C. Note that the structures are represented disproportionately to their real size. The GenBank numbers of the plasmids are shown in parentheses.