New research from the Wellcome Sanger Institute is mapping the spread of extremely drug-resistant (XDR) strains of Klebsiella pneumoniae through hospitals in Europe.

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As far as antibiotics go, our last line of defense are carbapenem antibiotics; when all other antibiotics fail in dealing with a certain infection, these are sent in to finish the job. However, a Europe-wide survey of the Enterobacteriaceae family of bacteria found that antibiotic-resistant strains of Klebsiella pneumoniae, an opportunistic pathogen that can cause respiratory and bloodstream infections in humans, are spreading through hospitals in Europe. The findings are based on samples taken from patients in 244 hospitals in 32 countries.

Cureless

“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,” says Dr. Sophia David, first author of the study.

It is estimated that carbapenem-resistant K. pneumoniae caused 341 deaths in Europe in 2007, a figure that grew to 2,094 by 2015 (a six-fold increase), the authors explain. This high number of deaths is owed to the fact that once carbapenems lose the ability to fight a population of antibiotic-resistant bacteria, doctors have very few options left. Infants, the elderly, and immuno-compromised individuals, whose bodies can’t take the strain of said options, are thus particularly at risk.

The survey, its authors write, is the largest of its kind and the first concrete step towards consistent surveillance of carbapenem-resistant bacteria in Europe. It was built from over 2,000 samples of K. pneumoniae collected from patients across 244 hospitals and sent to the Wellcome Sanger Institute, where the genomes of 1,700 of them were sequenced. The team identified a small cluster of genes that, when expressed, cause a strain to produce enzymes called carbapenemases that neutralizes the antibiotics.

The emergence of certain strains that carry one or more carbapenemase genes is of particular concern to public health, the authors explain, as these strains have spread relatively rapidly. Today’s heavy use of antibiotics in hospitals likely stacks the playing field in favor of these bacteria, the team adds, as they outcompete other strains that are more easily treatable with antibiotics. Samples used in the study were also more likely to be closely related to other samples in the same country rather than across countries, which suggests that national healthcare systems as a whole contribute to spread the strains around.

Not all is lost, however. The team explains that despite the deadliness of this carbapenem-resistant strains, infection control procedures in hospitals — ranging from consideration of how patients move between hospitals to hygiene interventions — still have an important impact.

“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,” says Professor Hajo Grundmann, co-lead author and Head of the Institute for Infection Prevention and Hospital Hygiene at the Medical Centre, University of Freiburg.

“This research emphasises 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 results were made available through MicroReact, a publicly-available web-based tool developed by the Centre for Genomic Pathogen Surveillance to help researchers and healthcare systems chart the spread of antibiotic resistance in pathogens like K. pneumoniae. A second survey is currently being planned.

“Genomic surveillance will be key to tackling the new breeds of antibiotic-resistant pathogen strains that this study has identified,” says Professor David Aanensen, co-lead author and Director of the Centre for Genomic Pathogen Surveillance.

“Currently, new strains are evolving almost as fast as we can sequence them. The goal to establish a robust network of genome sequencing hubs will allow healthcare systems to much more quickly track the spread of these bacteria and how they’re evolving.”

The paper “Epidemic of carbapenem-resistant Klebsiella pneumoniae in Europe is driven by nosocomial spread” has been published in the journal Nature Microbiology.