NEW YORK – Hospitals are a central link in the spread of drug-resistant Klebsiella pneumoniae in Europe, according to a new genomic analysis.
The number of deaths attributed to carbapenem-resistant K. pneumoniae is on the rise in Europe. In 2007, about 341 deaths there were caused by the bacterium, but in 2015, nearly 2,100 deaths were.
As part of the European Survey of Carbapenemase-Producing Enterobacteriaceae (EuSCAPE), a Wellcome Sanger Institute-led team collected more than 1,700 bacterial samples from 250 hospitals in 32 countries. Their phylogenetic analysis uncovered four clonal lineages of carbapenem-resistant K. pneumoniae and found that hospitals are a transmission hot spot, which indicates better infection control in hospitals is needed.
"In the case of carbapenem-resistant Klebsiella pneumoniae, our findings imply hospitals are the key facilitator of transmission — over half of the samples carrying a carbapenemase gene were closely related to others collected from the same hospital, suggesting that the bacteria are spreading from person to person primarily within hospitals," first author Sophia David, from Sanger's Center for Genomic Pathogen Surveillance, said in a statement. The findings were published today in Nature Microbiology.
For EUSCape, hospital laboratories across Europe were asked to submit their first 10 consecutive isolates of either K. pneumoniae or Escherichia coli that were not susceptible to carbapenem alongside isolates from the same species that were susceptible to carbapenem for analysis. Then for this paper, the researchers sequenced the genomes of the 1,717 K. pneumoniae isolates that were sent in during the survey.
Overall, 55 percent of the isolates submitted were thought to be non-susceptible to carbapenem and 45 percent were thought to be susceptible, and 96 percent of the isolates belonged to K. pneumoniae sensu stricto.
The researchers examined the isolates' genomes for known β-lactam resistance factors, and most of the isolates — 684 of them — carried one or more carbapenemase genes like blaKPC-like and blaOXA-48-like, among others. Most of these carbapenemase gene-containing strains, further, belonged to four K. pneumoniae lineages making up sequence types 11, 15, 101 and ST258/512, and their derivatives.
These four lineages, the researchers noted, have limited core genome diversity indicative of a recent and common evolutionary descent, despite their spread across Europe.
They then measured the genetic relatedness of their samples, and found that their genetically nearest neighbor was from the same hospital for 159 of the 311 isolates carrying the blaKPC-like gene, for 125 of the 248 isolates carrying the blaOXA-48-like gene, for 43 of 79 of those with the blaNDM-like gene, and for 42 of 56 carrying the blaVIM-like gene. This, they said, is indicative of frequent hospital transmissions.
"We are optimistic that with good hospital hygiene, which includes early identification and isolation of patients carrying these bacteria, we can not only delay the spread of these pathogens, but also successfully control them," Hajo Grundmann, co-senior author from the University of Freiburg, said in a statement. "This research emphasizes the importance of infection control and ongoing genomic surveillance of antibiotic-resistant bacteria to ensure we detect new resistant strains early and act to combat the spread of antibiotic resistance."
The researchers further traced the international spread of these resistance clones, and reported that, as expected, they likely first arose in the US before being introduced into Greece and Israel and then across Europe.
A second survey of Enterobacteriaceae among European hospitals is in the planning stages, according to the Sanger.