Genomic surveillance method detects multiple superbugs in hospitals

Researchers have developed a new genomic technique that can simultaneously track the spread of multiple superbugs in a hospital, which could help prevent and manage common hospital-acquired infections more quickly and effectively than ever before.

The proof-of-concept study, led by the Wellcome Sanger Institute, the University of Oslo, Fondazione IRCCS Policlinico San Matteo in Italy and collaborators, details a new deep sequencing approach that simultaneously captures all of a hospital’s common infectious bacteria. Current methods involve culturing and sequencing all of the pathogens separately, which is more time-consuming and labor-intensive.

Published on August 20 in the Microbial lancetThe study looked at the entire population of pathogenic bacteria found in several intensive care units (ICUs) and regular wards of hospitals during the first wave of the COVID-19 pandemic in 2020. The researchers were able to see what type of bacteria patients were suffering from, including well-known antibiotic-resistant pathogens present in hospitals.

They found that every ICU patient tested in the study was colonized with at least one of these treatment-resistant bacteria, while the majority were colonized with several of them 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 limit the spread of common bacteria that are resistant to multiple treatments.

Bacteria usually reside in or on the body without causing harm, which is called colonization. However, if certain strains enter the bloodstream due to a weakened immune system, they can cause serious and potentially fatal infections unless they can be effectively treated with antibiotics.

The fact that some of these bacteria are resistant to antibiotics poses an additional challenge for health care providers. Infections caused by these bacteria are a major problem in hospitals. These treatment-resistant bacteria are expected to cause more deaths than cancer by 2050. While some hospitals test for antibiotic-resistant bacteria upon arrival, there is no system that effectively tracks all multidrug-resistant bacteria in a hospital.

Over the past 15 years, genomic surveillance has become a powerful tool for tracking the evolution and transmission of pathogens, providing crucial information to help manage the spread of disease.

However, current methods involve culturing a single strain of bacteria at a time in a sample and then sequencing the entire genome of each strain separately. This is a laborious process, which can easily take several days and provides only a partial overview of all the clinically relevant bacteria found in a sample.

In this new study led by the Wellcome Sanger Institute, the University of Oslo, Fondazione IRCCS Policlinico San Matteo in Italy and collaborators, the team developed a new approach that captured whole genome sequencing data from multiple pathogens at once. This is a “pan-pathogen” deep sequencing approach that can provide genomic data as quickly as hospitals can process samples.

The team took samples from 256 patients at an Italian hospital, capturing bacteria from the gut, upper respiratory tract and lungs. The 2,418 DNA samples were matched to 52 species of bacteria. 66% (2,148) of them consisted of different strains of the seven most common bacterial infections seen in hospitals.

They found that intensive care unit patients were colonized with at least one bacteria likely to cause severe disease at any given time, and that clinically important AMR genes were present in at least 40% of them.

The team effectively mapped the spread of hospital bacteria over a five-week sampling period, which also allowed them to predict which bacteria were most likely to appear in infections acquired during the hospital stay.

Professor Jukka Corander, co-lead author from the Wellcome Sanger Institute and the University of Oslo, said: “Our method of capturing genetic information across multiple bacterial strains at the same time has the potential to transform genomic surveillance of pathogens, allowing us to capture critical information more quickly and comprehensively than ever before without losing resolution.

“With our proof-of-concept study, this approach can now be used with confidence in future research to capture the full range of high-risk bacteria in an area and, hopefully, by hospitals to help track and limit the spread of treatment-resistant bacteria.”

Dr Harry Thorpe, first author from the University of Oslo and visiting researcher at the Wellcome Sanger Institute, said: “Our study is an example of how we can use the power of genomics to create a comprehensive picture of antibiotic-resistant bacteria in intensive care units and also elsewhere in hospitals.

“Antibiotic-resistant bacteria are evolving and spreading rapidly, so our monitoring methods need to adapt to their evolution. Knowing the sequence of all the bacteria in a sample gives a more complete picture of the diversity present in an area, which is essential for predicting risk and understanding the external factors involved in the spread of a specific strain.”

Professor Fausto Baldanti, Director of the Microbiology and Virology Unit of the IRCCS Policlinico San Matteo Foundation, said: “Our unit detected the first case of COVID-19 in the Western world and we witnessed the dawn of the pandemic as well as the enormous global scientific effort on SARS-COV-2. However, the study of our researchers has shown that superbugs have not disappeared.

“Indeed, the simultaneous presence of several species of drug-resistant bacteria in intensive care units hosting patients with COVID-19 could have been a relevant element of the clinical manifestation of the new disease at this dramatic time.”

Professor Nicholas Thomson, co-lead author from the Wellcome Sanger Institute, said: “Antibiotic-resistant infections are a recurring problem in hospitals, and while healthcare professionals work hard to minimise them as much as possible, it’s difficult to tackle something you can’t fully see.

“Integrating a deep genomic sequencing approach into healthcare systems in this way gives people working in hospitals a new opportunity to see and track these bacteria, helping to diagnose infections and identify and control 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.”