Abstract
Carbapenem resistant Klebsiella pneumoniae (CR-KP) infections are an ever-increasing global issue, especially in the Indian subcontinent. Here we report genetic insight into a blaOXA-181 harbouring Klebsiella pneumoniae, belonging to the pandemic lineage ST147, that represents an intermediate stage towards pan-drug resistance. The CR-KP isolate DA48896 was isolated from a patient from Pakistan and was susceptible only to tigecycline and colistin. It harboured blaOXA-181 and was assigned to sequence type ST147. Analysis from whole genome sequencing revealed a very high sequence similarity to the previously sequenced pan-resistant K. pneumoniae isolate MS6671 from the United Arab Emirates. The two isolates are very closely related with only 46 chromosomal nucleotide differences, 14 indels and differences in plasmid content. Both carry a substantial number of plasmid-borne and chromosomally encoded resistance determinants. Interestingly, the two differences in susceptibility between the isolates could be attributed to DA48896 lacking an insertion of blaOXA-181 into the mgrB gene that results in colistin resistance in MS6671 and SNPs affecting AcrAB efflux pump expression likely to result in tigecycline resistance. These differences between the otherwise very similar isolates indicate that strong selection has occurred for resistance towards these last-resort drugs and illustrates the trajectory of resistance evolution of OXA-181-producing versions of the ST147 international risk clone.
Highlights
Over the last two decades carbapenems have emerged as last line of effective therapy for treating the worldwide disseminated extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae
In June 2015, a carbapenem resistant K. pneumoniae was isolated from the tracheal secretion and an endotracheal tube of a 32-year-old female patient at the intensive care unit at the tertiary hospital, Pakistan Institute of Medical sciences, Islamabad
The DA48896 strain was assigned to sequence type 147 and capsular serotype K64 and the chromosomal sequence had a very high sequence similarity to the previously sequenced K. pneumoniae isolate MS6671
Summary
Over the last two decades carbapenems have emerged as last line of effective therapy for treating the worldwide disseminated extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. Various studies from Pakistan have reported prevalence of ESBL-producing Klebsiella pneumoniae ranging from 26% to 59% during 2002 to 2013 [1,2,3,4]. There is a significantly increasing dependence upon carbapenems for treating such MDR K. pneumoniae. Carbapenemases in Enterobacteriaceae were relatively rare a decade ago, their. A blaOXA-181-harbouring multi-resistant ST147 Klebsiella pneumoniae isolate from Pakistan. Fellowships, 112-25656-2Bm1-034) and the International Research Support Initiative Program (29BMS46) to FN. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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