Clinical Utility of Plasma Microbial Cell-Free DNA Sequencing Among Immunocompromised Patients With Pneumonia.

Background

Plasma microbial cell-free DNA (mcfDNA) sequencing can establish the etiology of multiple infectious syndromes by identifying microbial DNA in plasma. However, data are needed to define the clinical scenarios where this tool offers the highest clinical benefit.

Methods

We conducted a prospective multicenter observational study that evaluated the impact of plasma mcfDNA sequencing compared with usual care testing among adults with hematologic malignancies. This is a secondary analysis of an expanded cohort that evaluated the clinical utility of plasma mcfDNA sequencing across prespecified and adjudicated outcomes. We examined the percentage of participants for whom plasma mcfDNA sequencing identified a probable cause of pneumonia or clinically relevant nonpneumonia infection. We then assessed potential changes in antimicrobial therapy based on plasma mcfDNA sequencing results and the potential for early mcfDNA testing to avoid bronchoscopy and its associated adverse events.

Results

Of 223 participants, at least 1 microbial detection by plasma mcfDNA sequencing was adjudicated as a probable cause of pneumonia in 57 (25.6%) and a clinically relevant nonpneumonia infection in 88 (39.5%). A probable cause of pneumonia was exclusively identified by plasma mcfDNA sequencing in 23 (10.3%) participants. Antimicrobial therapy would have changed for 41 (18.4%) participants had plasma mcfDNA results been available in real time. Among the 57 participants with a probable cause of pneumonia identified by plasma mcfDNA sequencing, bronchoscopy identified no additional probable cause of pneumonia in 52 (91.2%).

Conclusions

Plasma mcfDNA sequencing could improve management of both pneumonia and other concurrent infections in immunocompromised patients with suspected pneumonia.

Informations de copyright

© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

Déclaration de conflit d'intérêts

Potential conflicts of interest. Deng B. Madut reports receiving consulting fees from Karius. Roy F. Chemaly reports being a scientific advisor or consultant for ADMA Biologics, Pulmotec, Janssen, Merck/MSD, Partner Therapeutics, Takeda, Shinoigi, Genentech, Astellas, Adagio Therapeutics, Oxford Immunotec, Qiagen, Karius, Moderna, and Ansun Pharmaceuticals and received research grants paid to his institution from NIH/NCI, Merck/MSD, Karius, AiCuris, Ansun Pharmaceuticals, Takeda, Genentech, Oxford Immunotec, Freestyle, and Eurofins-Viracor. Sanjeet Dadwal reports research grants paid to his institution from Karius, Merck, Gilead, Ansun Biopharma, Allovir. He has served on advisory boards for Merck, Takeda, Allovir, and Aseptiscope, Inc. He is on speakers’ bureaus of Merck, Astellas, and Takeda and holds stock options in Aseptiscope, Inc. Joshua A. Hill reports research grants paid to his institution from Karius and consulting for Karius. He reports no other relevant conflicts of interest. Yeon Joo Lee has served as an investigator for Astellas, Karius, AiCuris, and Scynexis and has received research grant support from Merck & Co. Inc. Ghady Haidar is a recipient of research grants from Allovir, Karius, and AstraZeneca and also serves on the scientific advisory boards of Karius and AstraZeneca. Alfred Luk reports no relevant conflicts of interest. Alexander Drelick reports no relevant conflicts of interest. Peter V. Chin-Hong reports no relevant conflicts of interest. Esther Benamu reports no relevant conflicts of interest. Fareed Khawaja reports an honorarium from Medscape and research support from Eurofins-Viracor. Deepa Nanayakkara reports no relevant conflicts of interest. Genovefa A. Papanicolaou reports research support from MSD and Takeda/Shire and consulting and other fees from AlloVir, Amplyx, SLC Behring, Cidara, MSD, Takeda, and Octapharma. Catherine Butkus Small reports research grant support from NIH, GlaxoSmithKline, ViiV, Abbott, Merck, Gilead, Chimerix, Shire/Takeda, Schering-Plough, Ablynx, Janssen, Ansun Biopharma, and Karyopharm Therapeutics. Monica Fung reports research grant support from NIH. Michelle A. Barron reports no relevant conflicts of interest. Thomas Davis reports no relevant conflicts of interest. Micah T. McClain reports being a consultant for UpToDate and a co-inventor of patents on Methods to Detect and Treat Acute Respiratory Infections. Eileen K. Maziarz reports no relevant conflicts of interest. Armando D. Bedoya reports no relevant conflicts of interest. Daniel L. Gilstrap reports no relevant conflicts of interest. Jamie L. Todd reports advisory board participation for Sanofi, Natera, Theravance, and Altavant Sciences (now Enzyvant Therapeutics), in addition to grants to the institution from Boehringer-Ingelheim, AstraZeneca, and CareDx. Christina E. Barkauskas reports no relevant conflicts of interest. Madeleine R. Heldman reports receiving consulting fees from Karius and Medacorp. Robert Bigelow reports stock holdings in Merck, Johnson & Johnson, COVIDien, Pfizer, Sanofi, McKesson, and Viatris and consulting fees from Elixir. Jeffrey D. Leimberger reports no relevant conflicts of interest. Ephraim L. Tsalik reports personal fees from Biomeme, stock options in Danaher, and being an employee of Danaher Corp. Olivia Wolf reports no relevant conflicts of interest. Mona Mughar reports being an employee of Karius Inc., Redwood City, California, and may own stock options. Constance Lau reports being an employee of Karius Inc., Redwood City, California, and may own stock options. Nicholas Noll reports being an employee of Karius Inc., Redwood City, California, and may own stock options. Desiree Hollemon reports being a former employee of Karius Inc., Redwood City, California. Radha Duttagupta reports being a former employee of Karius Inc., Redwood City, California. Daniel S. Lupu reports being an employee of Karius Inc., Redwood City, California, and may own stock options. Sivan Bercovici reports being an employee of Karius Inc., Redwood City, California, and may own stock options. Bradley A. Perkins reports being an employee of Karius Inc., Redwood City, California, and may own stock options. Timothy A. Blauwkamp reports being an employee of Karius Inc., Redwood City, California, and may own stock options. Vance G. Fowler Jr. reports personal fees from Novartis, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co., MedImmune, Bayer, Basilea, Affinergy, Janssen, Contrafect, Regeneron, Destiny, Amphliphi Biosciences, Integrated Biotherapeutics, C3J, Armata, Valanbio, Akagera, Aridis, and Roche; grants from NIH, MedImmune, Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Merck, Medical Biosurfaces, Locus, Affinergy, Contrafect, Karius, Genentech, Regeneron, Deep Blue, Basilea, and Janssen; royalties from UpToDate; stock options from Valanbio and ArcBio; honoraria from the Infectious Diseases Society of America for his service as Associate Editor of Clinical Infectious Diseases; and a pending patent on sepsis diagnostics. Thomas L. Holland reports being an advisor and consultant to Aridis, Basilea Pharmaceutica, Karius, and Lysovant and royalties from UpToDate. Stephen P. Bergin reports being a consultant to C3J Therapeutics.