Metagenomic shotgun sequencing of blood to identify bacteria and viruses in leukemic febrile neutropenia.

Despite diagnostic advances in microbiology, the etiology of neutropenic fever remains elusive in most cases. In this study, we evaluated the utility of a metagenomic shotgun sequencing based assay for detection of bacteria and viruses in blood samples of patients with febrile neutropenia. We prospectively enrolled 20 acute leukemia patients and obtained blood from these patients at three time points: 1) anytime from onset of neutropenia until before development of neutropenic fever, 2) within 24 hours of onset of neutropenic fever, 3) 5-7 days after onset of neutropenic fever. Blood samples underwent sample preparation, sequencing and analysis using the iDTECT® Dx Blood v1® platform (PathoQuest, Paris, France). Clinically relevant viruses or bacteria were detected in three cases each by metagenomic shotgun sequencing and blood cultures, albeit with no concordance between the two. Further optimization of sample preparation methods and sequencing platforms is needed before widespread adoption of this technology into clinical practice.

Déclaration de conflit d'intérêts

M.M., C.R., S.C. and P.B. are employed by PathoQuest and own shares of PathoQuest. A.F. is a former employee of PathoQuest. M.R.S. reports receiving funds from TYRX Inc. and Medtronic for prior research unrelated to this study administered according to a sponsored research agreement between Mayo Clinic and study sponsor that prospectively defined the scope of the research effort and corresponding budget; and honoraria/consulting fees from Medtronic Inc. and Aziyo Biologics, Inc. Research Grant: Medtronic (significant - $40K), Honoraria: Medtronic (significant $20K), and Aziyo Biologics (modest $5K). M.M.P. serves on the Advisory Board for Kura Oncology. R.P reports grants from ContraFect, TenNor Therapeutics Limited, and BioFire. R.P. is or has been a consultant to Curetis, Specific Technologies, Next Gen Diagnostics, PathoQuest, Selux Diagnostics, 1928 Diagnostics, PhAST, Torus Biosystems, Day Zero Diagnostics, Mammoth Biosciences, CARB-X, and Qvella; monies are paid to Mayo Clinic. R.P. is also a consultant to Netflix. In addition, R.P. has a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued. R.P. receives travel reimbursement from ASM and IDSA and an editor’s stipend from IDSA, and honoraria from the NBME, Up-to-Date and the Infectious Diseases Board Review Course. All other authors report no potential conflicts of interest. this does not alter our adherence to PLOS ONE policies on sharing data and materials.