666 - Microbial Cell-Free DNA Sequencing for Evaluation of Response to Antibiotic Therapy in Patients with Relapsed or Refractory Leukemia

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Co-Author(s)

Joshua Wolf

Associate member
St. Jude Children's Research Hospital
Memphis, Tennessee
Disclosure: Karius inc (Grant/Research Support)
KG

Kathryn Goggin

Infectious diseases fellow
St. Jude’s Children’s Research Hospital
Memphis, Tennessee
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Ag

Amanda griffen

Laboratory technician
St. Jude Children's Research Hospital
Memphis, Tennessee
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
CK

Christina Kohler

Laboratory technician
St. Jude Children's Research Hospital
Memphis, Tennessee
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
KA

Kim J. Allison

Manager Clinical Research Operations
St. Jude Children's Research Hospital
Memphis, TN
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
YI

Yuki Inaba

Medical Student
UTSW
Dallas, Texas
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Asim A. Ahmed

Doctor
Karius
Redwood City, California
Disclosure: Karius (Employee)
DH

Desiree D. Hollemon

Head of Clinical Affairs
Karius, Inc
Redwood City, CA
Disclosure: Karius inc (Employee)
AB

Abigail Brenner

Medical Student
Indiana University
Indianapolis, Indiana
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Gabriela Maron

Associate Member
St. Jude Children's Research Hospital
Memphis, TN
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
YS

Yilun Sun

Statistician
St. Jude Children's Research Hospital
Memphis, Tennessee
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
LT

Li Tang

Associate Member
St. Jude Children's Research Hospital
Memphis, TN
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
CG

Charles Gawad

Assistant Professor
Stanford University
Stanford, California
Disclosure: Karius inc (Grant/Research Support)

Presenting Author(s)

EM

Ellie Margolis

Assistant Member
St. Jude Children's Research Hospital
Memphis, Tennessee
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.

Background: In patients with bloodstream infection (BSI), true eradication of infection takes longer than blood culture clearance. Therefore, optimal treatment duration, especially in immunocompromised hosts, is unknown. A sensitive test of microbiological response to treatment could improve care by indicating a time for safe antibiotic discontinuation. Microbial cell-free DNA sequencing (mcfDNA-seq) is a sensitive predictor of BSI, and we hypothesize that it might also be useful to measure response to treatment.

Methods: Eligible participants were < 25 years of age being treated for leukemia. Remnant plasma samples were collected as part of a prospective study (PREDSEQ) , and underwent mcfDNA-seq by Karius Inc. in a CLIA/CAP-accredited laboratory. Pathogen DNA was reported in molecules per microliter (MPM). Testing was batched and blinded. Available samples from Day 1 through Day 7 after onset of bacterial BSI were included. We evaluated decay of the BSI pathogen DNA after initiation of effective antibiotic therapy, from the peak to last available sample, and compared episodes with slow (< 0.5 log₁₀MPM/day) vs. rapid DNA decay.

Results:

There were 13 evaluable BSI episodes in 9 participants; 7 had slow DNA decay. Persistence of bacteremia or fever ≥1 day after initiation of effective antibiotics occurred in 9/13 episodes (7/7 slow decay and 2/6 rapid decay; P = 0.02). Slow decay persisted beyond resolution of bacteremia and fever in 3/7 of these cases.Figure 1. Pathogen DNA Concentration by mcfDNA-seq During Antibiotic Treatment of Bacteremia; Dashed line, blood culture positive; Red circle, last fever

Conclusion: In this small convenience sample of patients with leukemia, slow mcfDNA-seq DNA decay correlated with persistent fever or bacteremia. Post-BSI mcfDNA-seq monitoring should be investigated with the goal of decreasing inappropriate antibiotic therapy and preventing treatment failure.