751 - Karius Cell-Free DNA Metagenomic Assay of Plasma Detects Pulmonary and Disseminated Trichosporon Infections in Patients with Hematological Malignancies

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Co-Author(s)

Tempe K. Chen

Vice Chair, Pediatric Medicine
Miller Children's and Women's Hospital Long Beach
Long Beach, California
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)
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.
Joshua Wolf

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

Julie Chu

Attending Physician
Children’s Minnesota
Minneapolis/St Paul, Minnesota
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
BP

Bill Pomputius

Attending Physician
Children’s Minnesota
Minneapolis/St Paul, Minnesota
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
BB

Benjamin J. Briggs

Junior Faculty
UCSF
San Francisco, CA
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
MS

Melissa Sanacore

Lead Clinical Pharmacy Specialist
The Bone Marrow Transplant Program at Northside Hospital
Atlanta, Georgia
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
MS

Melhem M. Solh

Attending Physician
The Bone Marrow Transplant Program at Northside Hospital
Atlanta, Georgia
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
HH

H. Kent Holland

Attending Physician
The Bone Marrow Transplant Program at Northside Hospital
Atlanta, Georgia
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
AB

Asad Bashey

Attending Physician
The Bone Marrow Transplant Program at Northside Hospital
Atlanta, Georgia
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
LM

Lawrence Morris

Attending Physician
The Bone Marrow Transplant Program at Northside Hospital
Atlanta, Georgia
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
SS

Scott Solomon

Attending Physician
The Bone Marrow Transplant Program at Northside Hospital
Atlanta, Georgia
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
SW

Samuel Webster

Attending Physician
The Bone Marrow Transplant Program at Northside Hospital
Atlanta, Georgia
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.

Presenting Author(s)

TW

Thomas J. Walsh

Professor of Medicine, Pediatrics, Microbiology and Immunology
Weill Cornell Medicine and NYPH
New York, New York
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.

Background: Trichosporon species are uncommon but emerging pathogens that cause life-threatening infections that are resistant to amphotericin B and echinocandins. Diagnosis of deeply invasive trichosporonosis is often elusive to conventional culture methods until locally advanced or disseminated disease has advanced.CT scans Pulmonary Trichosporonosis

Lung Bx of Trichosporon detected by Karius Cell-Free DNA Metagenomic Assay of Plasma

Methods: Review of cases of next-generation sequencing of microbial cell-free DNA from plasma using the Karius-based technology for establishing a diagnosis of invasive trichosporonosis

Results: We found that next-generation sequencing of microbial cell-free DNA from plasma using the Karius-based technology established a diagnosis in six pediatric and adult patients. The median age was 17 yrs (8-72 yrs) all patients had underlying acute leukemia myelogenous leukemia. Six patients had pulmonary nodules and two also had multiple cutaneous lesions with negative blood cultures. Biopsies of one pulmonary nodule and of two cutaneous lesions revealed yeast-like cells. Culture of cutaneous lesions in two patients grew Trichosporon sp. Karius assays performed on plasma and analyzed against a database of more than 300 species of fungi identified Trichosporon asahii in two cases, Trichosporon spp. in three, Trichosporon faecale in one. In all cases, the metagenomic results defined therapy for treatment of invasive trichosporonosis, which is based in antifungal triazoles. In one patient with pulmonary nodules, lung biopsy revealed mixed septate and non-septate hyphal elements that later grew Trichosporon asahii, Rhizomucor pusillus, and Candida parapsilosis, all of which were identified by Karius assay.

Conclusion: Invasive Trichosporon spp. are uncommon polyene and triazole-resistant pathogens that cause life-threatening invasive fungal disease resistant in immunocompromised patient with hematological malignancies; next-generation sequencing of fungal cell-free DNA by Karius-based technology identified all six cases of pulmonary and disseminated trichosporonosis, contributing to early detection and pathogen-directed antifungal therapy.