Pan-pathogen deep sequencing could help tackle hospital infections, says Wellcome Sanger Institute

Researchers have developed a new genomic technique that can track the spread of multiple superbugs in a hospital simultaneously, which could help prevent infections taking hold or enable them to be managed more effectively.

The proof-of-concept study, from the Wellcome Sanger Institute, the University of Oslo, Fondazione IRCCS Policlinico San Matteo in Italy, and collaborators, deploys a new deep sequencing approach that captures all the common infectious bacteria in a hospital at once. Current methods take longer as all pathogens are cultured and sequenced separately.

Researchers believe the ‘pan-pathogen’ deep sequencing approach could be integrated with existing hospital clinical surveillance systems to identify, track and limit the spread of common multiple treatment-resistant bacteria at the same time.

Dr Harry Thorpe, first author from the University of Oslo and visiting worker at the Wellcome Sanger Institute, said: “Our study is an example of how we can use the power of genomics to create a full picture of antibiotic-resistant bacteria across intensive care units and also elsewhere in hospitals. Antibiotic-resistant bacteria evolve and spread quickly, and therefore our tracking methods have to keep pace with them. Knowing the sequencing of all the bacteria in a sample gives a more complete picture of the diversity found in an area, which is crucial in predicting risk and understanding the external factors involved in the spread of a specific strain.”

The team took samples from 256 patients in an Italian hospital and captured bacteria found in the gut, upper airways, and lungs. The 2,418 DNA samples were associated with 52 species of bacteria and 66 per cent (2,148) of these were made up of different strains of the seven most common bacterial infections seen in hospitals.

They found that patients in ICUs were colonised by at least one bacterium that had the potential to cause severe disease at any time. Clinically important anti-microbial resistant genes were present in at least 40 per cent of these.

The team mapped the spread of hospital bacteria across five weeks, allowing them to predict which bacteria were most likely to appear in infections acquired while in the hospital.

Prof Jukka Corander, co-senior author from the Wellcome Sanger Institute and the University of Oslo, said: “Our method that captures genetic information on multiple bacterial strains at the same time has the potential to transform the genomic surveillance of pathogens, enabling us to capture essential information both quicker and more comprehensively than ever before without losing resolution. With our proof-of-concept study, this approach can now confidently be used in future research to capture the full breadth of high-risk bacteria in an area, and hopefully by hospitals to help track and limit the spread of treatment-resistant bacteria.”

Prof Fausto Baldanti, director of the microbiology and birology unit at Fondazione IRCCS Policlinico San Matteo, said: “Our unit detected the first Covid-19 case in the Western world, and we witnessed the dawn of the pandemic along with the huge scientific effort worldwide on SARS-COV2. However, the study by our researchers showed that superbugs did not disappear. Indeed, the simultaneous presence of multiple species of drug-resistant bacteria in ICU wards admitting COVID-19 patients could have been a relevant component of the clinical manifestation of the new disease in those dramatic days.”

Prof Nicholas Thomson, co-senior author from the Wellcome Sanger Institute, added: “Antibiotic-resistant infections are an ongoing issue in hospitals, and while healthcare professionals work hard to minimise these as much as possible, it’s hard to fight against something you can’t fully see. Integrating a deep genomic sequencing approach into healthcare systems in this way gives those working in hospitals a new opportunity to see and track these bacteria, assisting in diagnosing infections and allowing outbreaks to be identified and controlled. Integration of this approach could help develop and improve guidelines for assessing and managing the risk of treatment-resistant infections for all the patients in a hospital, particularly those on intensive care units.”