Although it’s not yet ready for routine clinical practice, microbial cell-free DNA (mcfDNA) sequencing predicted three-quarters of bloodstream infections before they occurred among a small group of high-risk pediatric cancer patients participating in a pilot study (ClinicalTrials.gov Identifier: NCT03226158). The study results were recently published in JAMA Oncology.
The pilot study included 47 prospectively identified patients with relapsed or refractory cancers who were younger than 25 years and were being treated at St Jude Children’s Research Hospital in Memphis, Tennessee.
Blood samples were obtained within 7 days before a bloodstream infection occurred and at the time of the infection. Blood samples collected 7 days before or after a bloodstream infection from patients with no signs of fever or infection served as negative controls. To detect pathogens in the samples, mcfDNA sequencing was used.
A total of 19 bloodstream infection episodes occurred among 12 patients, and of these 19 episodes, 16 had predictive samples available, which spanned 15 bacterial bloodstream infection episodes. As for negative-control samples, 33 were included in the study.
At 3 days before a bloodstream infection, mcfDNA sequencing correctly predicted 12 of the 16 episodes, yielding a sensitivity of 75% (95% CI, 51%-90%), and 12 of the 15 bacterial episodes, yielding a sensitivity of 80% (95% CI, 55%-93%) for bacterial bloodstream infections. The specificity of mcfDNA sequencing for the negative control samples was 82% (95% CI, 66%-91%).
The study researchers cautioned that this specificity rate would make routine screening with mcfDNA sequencing “impractical” because of the “high” false-positive rate. The specificity did, however, increase to 91% (95% CI, 76%-97%) when mcfDNA sequencing screened for only common bloodstream infection pathogens.
- Goggin KP, Gonzalez-Pena V, Inaba Y, et al. Evaluation of plasma microbial cell-free DNA sequencing to predict bloodstream infection in pediatric patients with relapsed or refractory cancer [published online December 19, 2019]. JAMA Oncol. doi: 10.1001/jamaoncol.2019.4120