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A recent study led by Dr. Kumeren Govender from John Radcliffe Hospital highlighted the ability to use metagenomics for swiftly identifying bacteria from patients’ blood samples.
“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.”
Without a quick and suitable antibiotic treatment for patients, these types of infections often result in sepsis and multiple organ failure leading to death. Antimicrobial resistance continues to hinder treating different types of bacterial infections, as highlighted in a 2019 study that found drug-resistant infections within the bloodstream caused an estimated 370,000 deaths and was associated with nearly 1.5 million deaths1.
Current techniques used to identify pathogens from clinical samples often require culturing and testing that take several days to complete. While isolating and performing the antimicrobial susceptibility testing, patients’ infections worsen as they wait for the proper treatment. Conversely, utilizing metagenomic sequencing could allow clinicians to determine the genetic material from samples to reduce the waiting time.
Presenting his group’s work at this year’s European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) in Copenhagen, Denmark, Govender showed exactly how these metagenomics techniques could be deployed.
The research team began their study by randomly selecting 210 positive and 61 negative blood culture samples for examination at the Oxford University Hospital’s microbiology laboratory. The isolated DNA from the samples was sequenced with Oxford Nanopore’s GridION sequencer, and the resulting data was used to identify the pathogens, along with noting the common species present in the blood.
Using the sequencing data, the researchers identified 99% of the infecting pathogens, as well as the pathogens from polymicrobial infections and any contaminants. The group also found negative results in 100% of the samples determined to be culture negative. In addition, several of the metagenomics results were able to detect likely causes of infections that were missed by standard culturing methods and, in some instances, identify unculturable species where a result could not normally be resolved.
The metagenomic approach also detected antibiotic resistance from ten of the most frequent causes of these types of infections. Overall, the study included 741 resistant and 4047 combinations of antibiotics and pathogens showing that the metagenomic results and standard culturing methods agreed in 92% of the cases. When using just raw reads from a 2-hour sequencing run, the results still agreed at 90%.
After the extraction and sequencing process, the average time was around 4 hours with another 2 hours to achieve an antimicrobial resistance prediction. This method produces actionable results 18-42 hours ahead of standard testing procedures.
The co-author of the study, David Eyre, Professor of Infectious Diseases at the University of Oxford, stated, “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.”
References
“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.”
Without a quick and suitable antibiotic treatment for patients, these types of infections often result in sepsis and multiple organ failure leading to death. Antimicrobial resistance continues to hinder treating different types of bacterial infections, as highlighted in a 2019 study that found drug-resistant infections within the bloodstream caused an estimated 370,000 deaths and was associated with nearly 1.5 million deaths1.
Current techniques used to identify pathogens from clinical samples often require culturing and testing that take several days to complete. While isolating and performing the antimicrobial susceptibility testing, patients’ infections worsen as they wait for the proper treatment. Conversely, utilizing metagenomic sequencing could allow clinicians to determine the genetic material from samples to reduce the waiting time.
Presenting his group’s work at this year’s European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) in Copenhagen, Denmark, Govender showed exactly how these metagenomics techniques could be deployed.
The research team began their study by randomly selecting 210 positive and 61 negative blood culture samples for examination at the Oxford University Hospital’s microbiology laboratory. The isolated DNA from the samples was sequenced with Oxford Nanopore’s GridION sequencer, and the resulting data was used to identify the pathogens, along with noting the common species present in the blood.
Using the sequencing data, the researchers identified 99% of the infecting pathogens, as well as the pathogens from polymicrobial infections and any contaminants. The group also found negative results in 100% of the samples determined to be culture negative. In addition, several of the metagenomics results were able to detect likely causes of infections that were missed by standard culturing methods and, in some instances, identify unculturable species where a result could not normally be resolved.
The metagenomic approach also detected antibiotic resistance from ten of the most frequent causes of these types of infections. Overall, the study included 741 resistant and 4047 combinations of antibiotics and pathogens showing that the metagenomic results and standard culturing methods agreed in 92% of the cases. When using just raw reads from a 2-hour sequencing run, the results still agreed at 90%.
After the extraction and sequencing process, the average time was around 4 hours with another 2 hours to achieve an antimicrobial resistance prediction. This method produces actionable results 18-42 hours ahead of standard testing procedures.
The co-author of the study, David Eyre, Professor of Infectious Diseases at the University of Oxford, stated, “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.”
References
- Murray, Christopher JL, et al. "Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis." The Lancet 399.10325 (2022): 629-655.