870. Plasma microbial cell-free DNA sequencing impacts antimicrobial management in immunocompromised patients with pneumonia

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, FIDS