Rapid Metagenomics: A Powerful Tool for the Diagnosis of Pathogenic Organisms

According to recent research presented at this year’s European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) in Copenhagen, Denmark, metagenomic sequencing can also provide quick and actionable antimicrobial resistance predictions to treat bloodstream infections much faster than traditional laboratory tests and has the potential to save lives and help manage antibiotic use (15–18 April 2023).

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Dr. Kumeren Govender of the John Radcliffe Hospital, University of Oxford, conducted the research, which found that rapid metagenomics may offer correct results within six hours of knowing bacteria are growing in a blood sample.

Antibiotic resistant bloodstream infections are a leading killer in hospitals, and rapidly starting the right antibiotic saves lives. Our results suggests 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.”

Dr. Kumeren Govender, John Radcliffe Hospital, University of Oxford

Sepsis, multiple organ failure, and even death can result from bloodstream infections. Timely and appropriate antibiotic therapy is critical for infection management.

Antimicrobial resistance (AMR) is a significant challenge in the treatment of bloodstream infections, causing around 370,000 fatalities and being connected to over 1.5 million deaths in 2019.

The current method used in clinical settings to pinpoint the pathogen causing the infection is time-consuming and labor-intensive, requiring two time-consuming culture and sensitivity tests that take at least one to three days to complete—first isolating and identifying the pathogen, followed by antimicrobial susceptibility testing (exposing the bacteria to different antibiotics to identify exactly which it will respond to, and also the best route and dose).

Clinical metagenomics, on the other hand, sequences all of the genetic material in a sample at once; thus, time spent running tests, awaiting results, and performing more tests could be minimized.

To learn more, scientists randomly chose 210 positive and 61 negative blood culture specimens from the Oxford University Hospital’s microbiology laboratory for metagenomic sequencing between December 2020 and October 2022.

The Oxford Nanopore GridION platform was used to sequence the DNA. Sequences were used to determine pathogen species that cause infections as well as common species that can contaminate blood cultures.

Sequencing identified 99% of infecting pathogens, including polymicrobial infections and contaminants, and produced negative results in 100% of culture-negative samples. In some cases, sequencing discovered plausible causes of infection that regular cultures missed, while in others, it discovered uncultivable species where a result could not be ascertained.

Antibiotic resistance in the 10 most common causes of infection could also be determined via sequencing. A total of 741 resistant and 4,047 sensitive combinations of antibiotics and pathogens were investigated. Traditional culture-based testing and sequencing results agreed 92 percent of the time. After only two hours of sequencing, raw readings produced comparable results, with an overall agreement of 90%.

The average time from sample extraction to sequencing was four hours, with comprehensive AMR prediction two hours later, delivering actionable AMR results 18-42 hours earlier than in a traditional laboratory. David Eyre co-led the study.

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. 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.”

David Eyre, Professor of  Infectious Diseases, University of Oxford