Genome sequencing sheds light on deadly antibiotic resistant hospital infections

Laura Blackburn

1 October 2014

Antibiotic resistance is one of the most serious issues facing public health today and concern that many common infections could become untreatable has led to the issue becoming a key priority of governments worldwide. In the UK, antibiotic resistance has been added to the National Risk Register and the government has launched a  five-year strategy about how it plans to tackle the issue.

In particular, the increased incidence of infections caused by members of the bacterial group Enterobacteriacae that are resistant to antibiotics of last resort, carbapenems, is a great cause for concern within the health system. While many of these bacteria live harmlessly in the body, they can cause infections in vulnerable patient groups and the emergence of resistance to carbapenems could render many of the common infections caused by bacteria such as Salmonella sp., Klebsiella sp. and E. coli untreatable. Indeed, the severity of the threat associated with the spread of these infections in hospitals in England has led Public Health England to produce a toolkit advising infection control professionals on the most effective ways to mitigate this risk.

Antibiotic resistance genes in bacteria can be carried on small circular sections of DNA called plasmids as well as on their main bacterial chromosome. Plasmids are small enough to be transferred between bacterial species in a process known as horizontal gene transfer, which has raised concerns that resistance to carbapenems could spread in this way. Understanding how and when carbapenem resistance is acquired and spread, including the role of horizontal gene transfer, could help inform infection control practices in healthcare settings and reduce risk to patients.

Tracking the spread of carabapenem-resistant bacteria

Researchers in the National Institutes of Health Clinical Centre in the US have described in a recent paper in Science Translational Medicine how they used long-read sequencing of whole plasmids to track carbapenem-resistant bacteria in an intensive care unit, following an earlier outbreak. The accuracy and the coverage of the technique they used gave clear answers to how resistance spread in many cases, even when epidemiological data suggested a different pathway of transmission.

Out of the bacterial isolates taken from the patients and their rooms, the team identified 20 that carrying plasmids with carbapenem-resistance genes. While they found great genetic variety in the resistance plasmids, indicating many independent introductions of resistant bacteria into the hospital, they confirmed only one case of transmission within the hospital. This was lower than expected and suggested that infection control measures, such as hand hygiene, were effective.

They also demonstrated evidence of plasmid transfer in bacteria living in a biofilm in a sink drain, but not in any of the patients, which demonstrates, in this case at least, that resistance in patients was not caused by plasmid transfer from between two of the many bacterial species with which they were colonised.

Their results also teased apart how patients infected with the same bacteria, who had no obvious epidemiological links to each other, were independently infected by regional strains circulating in different hospitals, which were then introduced into the test hospital by these patients upon admission. Likewise, infections in two patients who had epidemiological links were shown to be independent of one another.

Targeted use of sequencing in infection control

These results show that genomic sequencing can be used to great effect to understand introduction and transmission of infections in hospitals, to confirm how effectively infection control practices are working, to confirm or disprove common assumptions about how infections and resistance are transmitted, and to allow the health system to target resources to where they are most needed. In this case resources were directed to surveillance upon admission, which is one of the four key areas in the PHE toolkit for managing the threat of carbapenem-resistant bacteria.

While the sequencing of bacterial genomes and/or plasmids can be cheaper and quicker than conventional methods in determining resistance (as is the case for tuberculosis), at this stage it is likely not cost-effective or practical to sequence the bacteria from all patients that enter a hospital. However developing a strategy that uses sequencing as part of regular surveillance of antibiotic resistance, or to understand individual outbreaks, could help ensure that infection control practices are carried out in the optimal way for each hospital, and prevent patients who bring in infections from spreading them any further. 

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