Cell-free DNA Sequencing Enhances Antimicrobial Management

The Impact of Next-Generation Sequencing Cell-free Pathogen DNA Test on Antimicrobial Management in Adults with Hematological Malignancies and Transplant Recipients with Suspected Infections

Collaborative Research Study Published in Transplantation and Cellular Therapy

_{James Yu¹, Juan D. Diaz², Steven C. Goldstein³, Rushang D. Patel³, Juan C. Varela³, Caralyn Reyenga³, Megan Smith³, Tori Smith³, Jason Balls³, Sarfraz Ahmad⁴, Shahram Mori³}

_{¹ Department of Internal Medicine, ²Section of Infectious Disease, ³Blood & Marrow Transplant}

_{Center, ⁴Gynecologic Oncology Program, AdventHealth Cancer Institute, Orlando, FL 32804}

Summary

Background: Infections in adult patients with hematological malignancies (HM) and stem cell transplant (SCT) recipients are a significant cause of morbidity and mortality. A timely diagnosis of infections can have a major impact on outcomes. Tools that help rule out infectious causes of fever can decrease antibiotic use, toxicities, hospitalization costs and potentially decrease antibiotic resistance in the long term.

Objective: We retrospectively evaluated the ability of cell-free DNA next-generation sequencing (NGS) test in the timely identification of pathogenic microorganisms, and its impact on the antimicrobial management of immunocompromised patients with hematologic malignancies.

Study Design: In the period between 2018-2020, ninety-five samples were reviewed, of which 31 adult patients (32 tests) had hematologic malignancies or were recipients of SCT. The NGS tests were performed in the following patients: a) patients with prolonged fever and negative conventional tests, b) persistent fever despite positive conventional test and appropriate antimicrobials, and c) afebrile patients with imaging suspicious for infection.

Results: The median time from fever to NGS sampling was five-days (range: 1-28). The median time to NGS results was two-days (range: 1-6). The NGS resulted in an escalation of antibiotics in 28% of cases (9/32) and de-escalation of antibiotics in 31% of cases (10/32). Overall, NGS testing changed management in nearly 59% (19/32) of patients. The sensitivity and specificity of NGS to detect clinically significant infection was 80% and 58%, respectively. The test identified uncommon and difficult to diagnose organisms such as Nocardia, Legionella, Toxoplasma and Pneumocystis jirovecii, resulting in rapid antimicrobial interventions.

Conclusion: In patients with HM or SCT recipients, microbial cell-free DNA sequencing allowed rapid and actionable treatment. This strategy can target appropriate antibiotic use, avoid over-treatment and potentially decrease the hospital length-of-stay.

Highlights

• Cell-free DNA (cfDNA) has reasonably high sensitivity and specificity.
• cfDNA rapidly identified opportunistic/fungal infection in immunocompromised patients.
• Identification can result in early intervention and better anti-microbial stewardship.
• cfDNA may help decrease unnecessary broad spectrum anti-microbial use.

For more information or to refer a patient, call Bone Marrow Transplant Nurse Navigators Austin Carroll, BSN, RN; Anna Cullivan, BSN, RN; Vielka Hernandez, RN; or Amber Sipes, RN, at Call407-303-2825.

Link to published article: https://www.tctjournal.org/article/S2666-6367(21)00712-0/abstract