Researchers have developed a new genomic technique that can track the spread of multiple superbugs simultaneously in a hospital, potentially helping prevent and treat common hospital infections more quickly and effectively than ever before.

The proof-of-concept study by the Wellcome Sanger Institute, the University of Oslo, the Fondazione IRCCS Policlinico San Matteo in Italy and collaborators describes a new approach to deep sequencing that captures all common infectious bacteria in a hospital at once. Current methods involve culturing and sequencing each pathogen separately, which takes longer and requires more work.

Published today (20 August) in Lancet microbeThe study covered the entire population of pathogenic bacteria found in several hospital intensive care units and regular wards during the first wave of the COVID-19 pandemic in 2020. The researchers were able to see what type of bacteria the patients had, including all known antibiotic-resistant pathogens found in hospitals.

They found that every intensive care patient tested in the study was colonized by at least one of these treatment-resistant bacteria, while the majority were colonized by several bacteria simultaneously.

The researchers believe their approach could be integrated into existing hospital clinical surveillance systems. Since drug resistance is a widespread problem in hospitals and other clinical settings, this system could simultaneously identify, track and contain the spread of common, multi-treatment-resistant bacteria.

Bacteria are normally found in or on the body without causing harm – this is called colonization. However, when certain strains enter the bloodstream due to a weakened immune system, they can cause serious and life-threatening infections unless they can be effectively treated with antibiotics.

An additional challenge for healthcare providers is that some of these bacteria are antibiotic resistant. Infections caused by AMR bacteria are a major problem in hospitals. It is predicted that these treatment-resistant bacteria will cause more deaths than cancer by 2050.¹While some hospitals test for AMR bacteria upon admission, there is no system that effectively detects all multidrug-resistant bacteria throughout the hospital.

Over the past 15 years, genome surveillance has become a powerful tool for tracking the evolution and transmission of pathogens and providing important insights for controlling disease spread.

However, current methods involve culturing only one bacterial strain in a sample at a time and then performing whole genome sequencing for all strains individually. This is a labor-intensive process that can easily take several days and provides only an incomplete snapshot of all clinically relevant bacteria found in a sample.

In this new study from the Wellcome Sanger Institute, the University of Oslo, the Fondazione IRCCS Policlinico San Matteo in Italy and collaborators, the team developed a new approach that captured whole genome sequencing data from multiple pathogens simultaneously. This is called a “pan-pathogenic” deep sequencing approach and can deliver genome data as fast as hospitals can process the samples.

The team took samples from 256 patients in an Italian hospital and recorded bacteria from the intestine, upper respiratory tract and lungs. The 2,418 DNA samples could be assigned to 52 bacterial species. 66 percent (2,148) of these consisted of different strains of the seven most common bacterial infections in hospitals.

They found that patients in intensive care units were colonized by at least one bacterium that could cause severe disease at any time, and that at least 40 percent of these patients had clinically significant AMR genes.

The team successfully mapped the distribution of hospital-acquired bacteria over a five-week sampling period, allowing them to predict which bacteria are most likely to be involved in hospital-acquired infections.

Our method, which captures genetic information across multiple bacterial strains simultaneously, has the potential to transform genomic surveillance of pathogens, allowing us to capture critical information faster and more comprehensively than ever before, without sacrificing resolution. With our proof-of-concept study, this approach can now be confidently used in future research to capture the full range of high-risk bacteria in an area, and hopefully by hospitals to track and contain the spread of treatment-resistant bacteria.”

Professor Jukka Corander, co-senior author from the Wellcome Sanger Institute and the University of Oslo

Dr Harry Thorpe, lead author from the University of Oslo and visiting scientist at the Wellcome Sanger Institute, said: “Our study is an example of how we can use the power of genomics to build a complete picture of antibiotic-resistant bacteria in intensive care units and elsewhere in hospitals. Antibiotic-resistant bacteria are evolving and spreading rapidly, and so our tracking methods need 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 for predicting risk and understanding the external factors involved in the spread of a particular strain.”

Professor Fausto Baldanti, Director of the Department of Microbiology and Virology at the Fondazione IRCCS Policlinico San Matteo, said: “Our department detected the first COVID-19 case in the Western world and we witnessed the outbreak of the pandemic as well as the enormous global scientific effort on SARS-COV2. However, the study by our researchers showed that the superbugs have not disappeared. In fact, the simultaneous presence of several species of drug-resistant bacteria in intensive care units where COVID-19 patients were admitted may have been a relevant component of the clinical manifestation of the new disease in these dramatic days.”

Professor Nicholas Thomson, co-senior author from the Wellcome Sanger Institute, said: “Antibiotic-resistant infections are an ongoing problem in hospitals and although healthcare professionals work hard to minimise them as much as possible, it is hard to tackle something you cannot fully see. Integrating a deep genome sequencing approach into healthcare systems in this way gives hospital workers a new way to see and track these bacteria, helping to diagnose infections and enable the identification and control of outbreaks. Integrating this approach could help develop and improve guidelines for assessing and managing the risk of treatment-resistant infections for all patients in a hospital, particularly those in intensive care units.”