Decisions about how to treat antimicrobial resistance can be made much faster with metagenomic sequencing than by conventional laboratory tests, new research shows. This approach could save lives and better manage care. In this study, rapid metagenomics provided accurate results within just six hours.
The new research was presented at the annual European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) in Copenhagen this week. The work was led by Kumeren Govender from the John Radcliffe Hospital, University of Oxford, U.K.
Bloodstream infections can rapidly lead to sepsis, multiple organ failure, and even death. It’s estimated that such infections cause 250,000 deaths each year in North America and Europe alone.
“Antibiotic-resistant bloodstream infections are a leading killer in hospitals, and rapidly starting the right antibiotic saves lives,” said Govender. “Our results suggest that metagenomics is a powerful tool for the rapid and accurate diagnosis of pathogenic organisms and antimicrobial resistance, allowing for effective treatment 18 to 42 hours earlier than would be possible using standard culture techniques.”
The current method used in clinical settings to identify a pathogen involves two culture and sensitivity tests that take at least 1 to 3 days to complete—first isolating and identifying the pathogen and then performing antimicrobial susceptibility testing to which antibiotics it will respond to, plus the best route and dose.
In contrast, using clinical metagenomics all the genetic material is sequenced, including infectious pathogens, in a sample all at once. Time spent running tests, waiting for results, and running more tests could be reduced.
The researchers randomly selected 210 positive and 61 negative blood culture specimens for metagenomic sequencing from the Oxford University Hospital’s microbiology laboratory between December 2020 and October 2022.
DNA was sequenced using the Oxford Nanopore GridION platform. Sequences were used to identify the species of pathogen causing infections and also to spot common species that can contaminate blood cultures.
Sequencing was able to identify 99% of infecting pathogens including polymicrobial infections and contaminants, as well as giving negative results in 100% of culture negative samples. In some instances, sequencing detected probable causes of infection missed by routine cultures, and in other instances, it identified uncultivable species where a result could not be determined.
Sequencing could also be used to detect antibiotic resistance in the ten most common causes of infections. A total of 741 resistant and 4047 sensitive combinations of antibiotics and pathogens were studied. Results of traditional culture-based testing and sequencing agreed 92% of the time. Similar performance could be obtained from raw reads after only two hours of sequencing, overall agreement was 90%.
The average time from sample extraction to sequencing was four hours with complete AMR prediction two hours later, producing actionable AMR results 18–42 hours before the conventional laboratory.
David Eyre, DPhil, professor of infectious diseases at the University of Oxford, who co-led the study, said, “This is a really exciting breakthrough that means we will be able to diagnose the cause of patients’ infections faster and more completely than has been possible before.”
He added, “We are working hard to continue to overcome some of the remaining barriers to metagenomic sequencing being used more widely, which include its current high cost, further improving accuracy, and creating improved laboratory expertise in these new technologies and simpler workflows for interpreting results.”
