A new study found that the Karius Test, which uses microbial cell-free DNA (mcfDNA-seq), can predict bloodstream infections in leukemia patients up to three days before the onset of symptoms. This is the first evidence the test can predict infections. Investigators at St. Jude Children’s Research Hospital used the test to identify bacteria that cause blood infections in 12 samples out of 16 tested—a 75% success rate. The paper was published in JAMA Oncology online today, and the lead author is Kathryn P. Goggin.
Bloodstream infections are especially common among patients undergoing treatment for leukemia. Some patients die from these infections rather than their cancer. Timely detection of dangerous pathogens is thus very important, but no reliable test for predicting infections has been available, according to the study authors.
“In a patient who is severely ill, the risk of not getting the right antibiotic early is very high,” explained Asim Ahmed, M.D., senior medical director, Karius. Prophylactic antibiotics are sometimes used to preemptively treat infections but are effective only 50% of the time and can lead to gastrointestinal symptoms and antibiotic resistance. Suspected infections are treated with antibiotics once symptoms develop, but this can be too late to prevent permanent damage or death in some cases.
“Parents of children with cancer often wish that they had a crystal ball to know what’s coming next; this might just be that…” said Josh Wolf, M.D., Ph.D., co-author and associate member of the Department of Infectious Diseases at St. Jude Children’s Research Hospital, in a company press release.
The study enrolled 47 pediatric patients with relapsed or refractory leukemia, of whom 12 experienced a total of 19 episodes of bloodstream infections over the study period. Across those episodes, there were samples available to evaluate the test’s predictive accuracy in 16 cases. The test correctly flagged infections in 75% of those cases.
The Karius Test is a CLIA-certified/CAP-accredited next-generation sequencing (NGS) plasma test that detects mcfDNA. After mcfDNA is extracted from the blood sample and NGS performed, human sequences are removed and remaining sequences are aligned to a curated pathogen database of >1,400 organisms. The test detects bacteria, DNA viruses, fungi, and parasites. It’s also very rapid, delivering results as quickly as in one day.
The test has been commercially available since 2016, and is currently used by over 100 institutions, according to Karius. Applications include complicated pneumonia, immunocompromised patients, and endocarditis. In some cases, these infections are currently diagnosed using a tissue sample, which adds to the patient’s discomfort and risk.
“Among the advantages of this test even if the patient is already taking antibiotics it still picks up a signal,” Ahmed told Clinical OMICs. “So besides predicting infections you can also use it to follow response to treatment.”
Ahmed explained that mcfDNA-seq has been used in research for a long time, there were major hurdles to its clinical application. “The main problem is that there is a lot of noise in the bloodstream,” he said. “You must be able to pick up the signal from the infectious agent over the background noise and be able to assess the microbiome versus human DNA.”
He also noted that: “The Karius Test is not currently a screening test; additional studies are needed to guide how this test can be used in the clinical work-flow to help predict and prevent infections in patients with immunocompromising conditions.” In their press release, Karius announced that this St. Jude’s study will be expanded to further analyze their test’s ability to identify bloodstream. infections before symptoms arise.