870. Plasma microbial cell-free DNA sequencing impacts antimicrobial management in immunocompromised patients with pneumonia
Authors: Madut Deng B , Chemaly Roy F , Dadwal Sanjeet S , Hill Joshua A , Lee Yeon Joo , Haidar Ghady , Luk Alfred , Drelick Alexander Christian , Chin-Hong Peter V , Benamu Esther , Khawaja Fareed , Nanayakkara Deepa D , Papanicolaou Genovefa , Small Catherine , Fung Monica , Barron Michelle , Davis Thomas , McClain Micah T , Maziarz Eileen K , Bedoya Armando , Gilstrap Daniel , Todd Jamie , Heldman Madeleine R , Barkauskaus Christina , Bigelow Robert , Leimberger Jeffrey , Tsalik Ephraim , Wolf Olivia , Mughar Mona , Hollemon Desiree , Duttagupta Radha , Lupu Daniel , Bercovici Sivan , Perkins Bradley A , Blauwkamp Timothy A , Fowler Vance G , Holland Thomas L , Bergin Stephen P 
Published: November 2023

Abstract

Background
Microbial cell-free DNA (mcfDNA) sequencing can establish the etiology of multiple infectious syndromes by identifying pathogen DNA from the plasma of infected patients. Here, we describe the potential impact of a positive mcfDNA result on clinical decision making among immunocompromised adults with suspected pneumonia.

Methods
This prospective observational study evaluated the potential utility of mcfDNA sequencing in adults with active hematological malignancies undergoing a diagnostic bronchoscopy for pneumonia at 10 US Medical Centers as part of the PICKUP Study (Abstract # 544 IDWeek 2022). Plasma mcfDNA was collected on all participants at the time of bronchoscopy. Clinical impact of the mcfDNA sequencing results vs usual care (UC) testing – including bronchoscopy- were adjudicated and then compared for: 1) identification of probable cause of pneumonia or clinically significant non-pulmonary infection and 2) potential changes to antimicrobial therapy if mcfDNA sequencing results were available to treating clinicians.

Results
Of 223 participants analyzed, median (IQR) age was 62 (50-69) years and 72 (32.3%) were female. Plasma mcfDNA identified a probable cause of pneumonia in 57/223 (25.6%, 95% CI 20.0-31.8) participants and could have changed antimicrobial therapy in 21/57 (36.8%, 95% CI 24.4-50.7). A probable cause of pneumonia was identified by mcfDNA in 23/223 (10.3%, 95% CI 6.7-15.1) participants when no cause was identified by UC, and these detections could have resulted in an antimicrobial change in 17/23 (73.9%, 95% CI 51.6-89.8). A clinically relevant non-pulmonary infection was identified in 88/223 (39.5%, 95% CI 33.0-46.2) participants and antimicrobial therapy could have changed in 22/88 (25.0%, 95% CI 16.4-35.4). Collectively, antimicrobial therapy could have changed for 41/223 (18.4%, 95% CI 13.5-24.1) participants if mcfDNA results were available to treating clinicians.

Conclusion
Positive plasma mcfDNA sequencing results could have supported changes in clinical management for pneumonia and non-pulmonary infections among immunocompromised patients undergoing bronchoscopy. Further studies are needed to refine the optimal timing of mcfDNA in relation to UC testing and establish the impact of real-time mcfDNA results on patient outcomes.

Disclosures
Deng B. Madut, MD, Karius: Advisor/Consultant Roy F. Chemaly, MD/MPH, Eurofins-VViracor: Grant/Research Support|Karius: Advisor/Consultant Sanjeet S. Dadwal, MD, FACP, FIDSA, Allovir: Advisor/Consultant|Allovir: Grant/Research Support|Ansun Biopharma: Grant/Research Support|Aseptiscope, Inc: Stocks/Bonds|Astellas: Honoraria|Karius: Grant/Research Support|Matinas Biopharma: Stocks/Bonds|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer/Amplyx: Grant/Research Support|Takeda: Advisor/Consultant|Takeda: Honoraria|Viracor: Honoraria Joshua A. Hill, MD, Allovir: Advisor/Consultant|Allovir: Grant/Research Support|Century Therapeutics: Advisor/Consultant|Covance/CSL: Advisor/Consultant|Deverra: Grant/Research Support|Eversana Life Science Services, LLC: Advisor/Consultant|GeoVax: Grant/Research Support|Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Karius: Advisor/Consultant|Karius: Grant/Research Support|Merck: Grant/Research Support|Moderna DSMB: Advisor/Consultant|Octapharma AG: Advisor/Consultant|OptumHealth: Advisor/Consultant|Oxford Immunotec: Grant/Research Support|Pfizer (previously Amplyx/Medpace): Advisor/Consultant|Senti BioSciences, Inc: Advisor/Consultant|Symbio: Advisor/Consultant|Takeda: Advisor/Consultant|Takeda: Grant/Research Support|Up-to-Date: Advisor/Consultant Yeon Joo Lee, MD, MPH, AiCuris: institutional research support for clinical trials|Karius: institutional research support for clinical trials|Merck: Grant/Research Support|Scynexis: institutional research support for clinical trials Ghady Haidar, MD, Allovir: Grant/Research Support|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|Karius: Advisor/Consultant|Karius: Grant/Research Support|NIH: Grant/Research Support Alfred Luk, MD, Bill & Melinda Gates Foundation: Grant/Research Support|Karius: Advisor/Consultant|Karius: Grant/Research Support Fareed Khawaja, MBBS, MEDSCAPE: Honoraria|Viracor: Grant/Research Support Genovefa Papanicolaou, MD, Allovir: Advisor/Consultant|Amplyx: Advisor/Consultant|Astellas: Advisor/Consultant|Cidara: Advisor/Consultant|CSL Behring: Advisor/Consultant|DSMC: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: institutional research support for clinical trials|MSD: Advisor/Consultant|Octapharma: Advisor/Consultant|Partners Rx: Advisor/Consultant|Shire/Takeda: institutional research support for clinical trials|Symbio: Advisor/Consultant|Symbio: Advisor/Consultant|Takeda: Advisor/Consultant|Vera Pharma: Advisor/Consultant Micah T. McClain, MD, PhD, Biomeme Inc: Methods to diagnose and treat acute respiratory infections Eileen K. Maziarz, MD, Karius, Inc: Advisor/Consultant Robert Bigelow, PhD, Covidien: Stocks/Bonds|Elixir Medical: Advisor/Consultant|Johnson & Johnson: Stocks/Bonds|Mckesson: Stocks/Bonds|Merck: Stocks/Bonds|Organon: Stocks/Bonds|Pfizer: Stocks/Bonds|Sanofi: Stocks/Bonds|Viatris: Stocks/Bonds Daniel Lupu, MD, PHD, Karius Inc: Employee|Karius Inc: Stocks/Bonds Sivan Bercovici, PhD, Karius: Stocks/Bonds Bradley A. Perkins, MD, Karius, Inc: Stocks/Bonds Timothy A. Blauwkamp, PhD, Karius: Board Member|Karius: Ownership Interest Vance G. Fowler, MD, MHS, Amphliphi Biosciences, Integrated Biotherapeutics; C3J, Armata, Valanbio; Akagera, Aridis, Roche, Astra Zeneca: Advisor/Consultant|Genentech, Regeneron, Deep Blue, Basilea, Janssen;: Grant/Research Support|Infectious Diseases Society of America: Honoraria|MedImmune, Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Merck; Medical Biosurfaces; Locus; Affinergy; Contrafect; Karius;: Grant/Research Support|Novartis, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co., MedImmune, Bayer, Basilea, Affinergy, Janssen, Contrafect, Regeneron, Destiny,: Advisor/Consultant|Sepsis diagnostic: Patent pending|UpToDate: Royalties|Valanbio and ArcBio: Stock Options Thomas L. Holland, MD, Aridis: Advisor/Consultant|Basilea Pharmaceutica: Advisor/Consultant|Karius: Advisor/Consultant|Lysovant: Advisor/Consultant Stephen P. Bergin, MD, Karius, Inc.: Grant/Research Support