A new genomic sequencing technique could help hospitals better track and control the spread of multiple drug-resistant pathogens, researchers reported yesterday in The Lancet Microbe.
The findings are from a proof-of-concept study led by scientists from the University of Olso, the Wellcome Trust Sanger Institute, and Fondazione IRCCS Policlinico San Matteo in Italy. Conducted in a hospital in a region of northern Italy that was one of the hardest hit by the first wave of the COVID-19 pandemic in 2020, the researchers used a pan-pathogen deep-sequencing approach to characterize the bacterial pathogen population in several intensive care units (ICUs) and ordinary hospital wards over a 5-week period.
They were also able to detect the antimicrobial resistance (AMR)-associated genes present in the hospital and track how these pathogens spread among patients.
"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," first author Harry Thorpe, PhD, of the University of Oslo, said in a Wellcome press release.
Technique used to track seven pathogens of interest
The technique used by Thorpe and his colleagues in the study differs from whole-genome sequencing (WGS), which is the standard approach for tracking the evolution and transmission of individual species of bacterial pathogens in hospitals. The drawback of WGS, they explain, is that it provides only a "partial snapshot" of bacterial diversity within a clinical sample, and sequencing multiple bacterial colonies in a clinical sample is time-consuming.
To capture WGS data from multiple bacterial pathogens at once, they developed an approach in which they enrich bacteria by culturing in selective media then deep-sequence all the bacterial DNA present. An algorithm developed by the team reconstructs individual bacterial genomes from the sequencing data.
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.
They then tested this approach in an 800-bed teaching hospital in Italy's Lombardy region during the first wave of the pandemic in spring 2020.
"Northern Italy has a high burden of AMR infections and was the first region in Europe to be severely affected by COVID-19; such conditions presented serious challenges to infection control, risking increased nosocomial transmission of bacterial pathogens," the study authors wrote.
From a cohort of 256 patients admitted to the hospital from March 1 to May 7, 2020, the researchers collected nasal, respiratory, and rectal samples, then cultured them, focusing on enrichment of seven pathogens that are the most common causes of drug-resistant, hospital-associated infections: Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecium, Enterococcus faecalis, Escherichia coli, and Staphylococcus aureus.
Presence of pathogens highest in ICUs
Of the 2,418 DNA samples that were sequenced, 2,148 belonged to the species of interest, and 55 sequence clusters from these bacterial species were detected at least five times. The presence of these pathogens was highest in the hospital's ICUs, with A baumannii, K pneumoniae, P aeruginosa, and E faecium most significantly associated with ICUs.
"These pathogens were found to be colonising multiple body sites in a typical ICU patient; this is probably due to the high hospital prevalence of the pathogens and severely ill state of the patients, but it might also have been a consequence of the difficult situation regarding infection control during the early pandemic," the authors wrote.
The prevalence of clinically important AMR genes was also higher in the ICUs than in the hospital's general wards, with several carbapenemase and extended-spectrum beta lactamase (ESBL) genes found in at least 50 (40%) of the 125 ICU patients.
In addition, the researchers were able to determine through deep sequencing that hospital transmission was likely a significant mode of acquiring these pathogens, particularly for A baumannii, K pneumoniae, P aeruginosa, and E faecium. More than 75% of the occurrences of these pathogens in patients was potentially linked to within-hospital transmission.
Although the accuracy, cost, and feasibility of the deep-sequencing technique needs to be further assessed, co-author Nicholas Thomson, PhD, of the Wellcome Sanger Institute says integrating it with existing surveillance systems could give hospitals a better way to "see and track" the drug-resistant pathogens that are such a significant cause of morbidity and mortality in hospital patients.
"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," he said. "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."
