983. Use of plasma-based microbial cell-free DNA (mcfDNA) sequencing for surveillance of infection in the 1st month after lung transplant (LT): a prospective, observational, pilot study
Authors: Haidar Ghady , Friday Kelly , Musgrove Christopher , Wang Xiaohong , Pisarra Angela , Hughes Kramer Kailey , Noda Kentaro , Ryssel Naomi , Craig Andrew , Blauwkamp Timothy A , Morrell Matthew , Hage Chadi , Snyder Mark , Sanchez Pablo , Morris Alison , Kitsios Georgios 
Published: November 2023

Abstract

Background
Infections after LT are common, but standard of care testing (SOCT) often fails to identify a cause. We prospectively compared longitudinal mcfDNA sequencing vs SOCT to determine the utility of mcfDNA sequencing for infection surveillance after LT.

Methods
Single center prospective observational study of new LT patients (pts). We collected plasma on days 0, 1, 2, 3, 7, 14, and 30 post LT for mcfDNA sequencing; results were not available clinically. We reviewed outcomes and SOCT through 6 months (mo).

Results
We enrolled 30 LT pts (4/2021-12/2022, Table 1). 93.3% (28/30) received broad-spectrum antibiotics, although only 40.0% (12/30) had SOCT yielding pathogenic bacteria. 43.33% (13/30) had unexplained leukocytosis. Table 2 shows serial mcfDNA sequencing results, clinical course, and adjudication of mcfDNA sequencing. 96% (29/30) had at least 1 positive mcfDNA sequencing test, including 68.75% (11/16) with presumed infection or unexplained leukocytosis and negative SOCT, but diversity of organisms on mcfDNA sequencing, e.g., Candida, oral or gastrointestinal commensals, Enterococci, or obligate pathogens (Enterobacter, Pseudomonas, Mycoplasma, Ureaplasma, others); most had polymicrobial mcfDNA sequencing results. In 36.67% (11/30), mcfDNA sequencing detected pathogens of unclear significance (potential false positive, FP). In 8 pts with positive SOCT, mcfDNA sequencing did not detect at least 1 pathogen found on SOCT. In 13% (4/30), mcfDNA sequencing detected a pathogen before it was detected by SOCT (n=1 each): VRE surgical site infection (SSI), invasive candidiasis, Enterobacter pneumonia, and M. hominis SSI (a known donor-derived syndrome) with HHV-8/Kaposi Sarcoma [presumed donor-derived due to donor risk factors, diagnosed on autopsy, pt 19].
Table 1.
Table 2 legend.
Table 2.

Conclusion
Plasma mcfDNA sequencing revealed potential occult explanations for unexplained leukocytosis and infectious syndromes with negative SOCT early post LT. mcfDNA sequencing also detected infection earlier than SOCT in 4 pts but did not detect known pathogens from 8 pts; &gt; 1/3 had presumed FP mcfDNA sequencing results. Larger studies with longer follow-up are needed to determine the utility of mcfDNA sequencing in diagnosing infection, optimizing antibiotic use, and monitoring donor-derived infection post LT.

Disclosures
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 Timothy A. Blauwkamp, PhD, Karius: Board Member|Karius: Ownership Interest Georgios Kitsios, MD, PhD, Karius, Inc: Grant/Research Support