Rapid Metagenomics Diagnoses Antibiotic Resistant Bloodstream Infections 18-42 Hours Faster Than Conventional Tests

Bloodstream infections can quickly progress to sepsis, multiple organ failure, and even death. Timely and appropriate antibiotic therapy is crucial for managing the infection. Antimicrobial resistance (AMR) poses a significant challenge in treating bloodstream infections. Current clinical methods for identifying the causative pathogen are lengthy and labor-intensive, involving 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. Now, new research presented at ECCMID 2023 demonstrates that metagenomic sequencing can offer rapid and actionable AMR predictions for treating bloodstream infections much faster than traditional laboratory tests, potentially saving lives and improving antibiotic management.

The study conducted by researchers at the University of Oxford (Oxford, UK) reveals that rapid metagenomics can provide accurate results within just six hours of detecting bacterial growth in a blood sample. Clinical metagenomics sequences all genetic material, including infectious pathogens, in a sample simultaneously, reducing the time spent on running tests, waiting for results, and conducting additional tests. For their study, the Oxford researchers randomly selected 210 positive and 61 negative blood culture specimens for metagenomic sequencing, using the Oxford Nanopore GridION platform to sequence DNA. The sequences were utilized to identify the pathogen species causing infections and to detect common species that can contaminate blood cultures.

Sequencing successfully identified 99% of infecting pathogens, including polymicrobial infections and contaminants, and yielded negative results in 100% of culture-negative samples. In some cases, sequencing detected probable infection causes that routine cultures missed, while in others, it identified uncultivable species when a result could not be determined. Sequencing could also detect antibiotic resistance in the 10 most common infection causes. A total of 741 resistant and 4047 sensitive antibiotic-pathogen combinations were examined, with traditional culture-based testing and sequencing results agreeing 92% of the time. Comparable performance could be achieved using raw reads after just two hours of sequencing, with an overall agreement of 90%. The average time from sample extraction to sequencing was four hours, with complete AMR prediction achieved two hours later, providing actionable AMR results 18-42 hours sooner than conventional laboratory methods.

“Antibiotic resistant bloodstream infections are a leading killer in hospitals, and rapidly starting the right antibiotic saves lives,” said Dr. Kumeren Govender from the John Radcliffe Hospital, University of Oxford, who led the study. “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.”

“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,” added David Eyre, Professor of Infectious Diseases at the University of Oxford, who co-led the study. “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.”

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