Novel Plasma Test Identifies Wide Range of Pathogens in Suspected Sepsis

Lab Medicine

Scientists from the Stanford University Medical Center used a new diagnostic test that could accurately identify the cause of sepsis, which enables to determine the most effective and appropriate antimicrobial therapy. The study was presented at the annual meeting of the Infectious Diseases Society of America (IDSA) held October 4-8, 2017, in San Diego, CA, USA.

Sepsis is a leading cause of death and can be caused by a wide range of potential pathogens. The causative pathogens are not always identified in 40% of cases. Hence there is a need for advanced diagnostic tests that can accurately detect the breadth of potential pathogens to determine adequate antimicrobial treatment.

The study involved a prospective group of patients presenting to the hospital with signs and symptoms of sepsis. Plasma samples were received for next-generation sequencing (NGS) testing at the time of initial blood culture. DNA present in the extracted plasma was sequenced, and human sequences were removed. Later, remaining reads aligned against a pathogen database consisting of bacteria, viruses, and eukaryotic pathogens.

Relative abundance was determined, and pathogens present at high statistical significance were identified. The results obtained from the NGS were compared with the composite reference standard of all microbiology testing performed within seven days of admission and clinical diagnosis.

The researchers collected the plasma from the 286 patients and detected the pathogens by Karius Plasma Next-Generation Sequencing assay. The team could find the pathogens in 172 sepsis patients including DNA viruses, fungi, and bacteria (even Mycobacterium tuberculosis).

In contrast, Out of 286 patients, 45 had a positive initial blood culture, and 109 had a potential infectious etiology identified using a composite microbiology laboratory standard. The NGS plasma test had a positive agreement of 39/45 (86.7%) compared to initial blood culture and 78/98 (79.5%) when compared to composite laboratory reference standard.

The Karius plasma NGS test identified a wide range of pathogens from a single sample of septic patients and identified three times more often than blood culture and more often than the combination of all microbiology tests. Hence the new diagnosis approach could aid healthcare providers to determine the effective antimicrobial treatment for the patients with sepsis, authors concluded.