Concordance of Noninvasive Plasma Cell-free DNA With Invasive Diagnostics for Diagnosis of Invasive Fungal Disease

Anthony Lieu1,2,3, Alex N Zimmet1, Joseph Pozdol4

  • 1Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, California, USA.

Abstract

Insights

Noninvasive mold plasma cell-free DNA (cfDNA) polymerase chain reaction (PCR) testing shows high accuracy for diagnosing invasive mold disease (IMD). This suggests that invasive specimen collection can be reduced in immunocompromised patients.

Area of Science:

  • Mycology
  • Infectious Diseases
  • Molecular Diagnostics

Background:

  • Invasive mold disease (IMD) diagnosis in immunocompromised patients often relies on invasive procedures.
  • Mold plasma cell-free DNA (cfDNA) polymerase chain reaction (PCR) offers a promising noninvasive alternative for early IMD detection.
  • The clinical utility of invasive specimen collection after plasma cfDNA PCR testing remains uncertain.

Purpose of the Study:

  • To evaluate the concordance between mold plasma cfDNA PCR results and conventional fungal diagnostic tests from invasive specimens.
  • To determine if invasive procedures can be safely reduced following noninvasive cfDNA PCR testing.

Main Methods:

  • Retrospective cohort study of 506 patients with mold plasma cfDNA PCR performed around the time of invasive specimen collection.
  • Invasive procedures included tissue biopsy and bronchoscopy.
  • Concordance was assessed between mold plasma cfDNA PCR and fungal tests on tissue/bronchoalveolar lavage fluid, adjudicated by EORTC/MSC guidelines.

Main Results:

  • Overall concordance between mold plasma cfDNA PCR and invasive tests was 88.5% (448/506).
  • In proven IMD cases, 64.7% (11/17) of negative mold plasma cfDNA PCR results were observed in patients with fungal sinusitis or limb infections.
  • Nonhematologic malignancy and nonneutropenic status were linked to negative mold plasma cfDNA PCR in proven/probable IMD.

Conclusions:

  • Noninvasive mold plasma cfDNA PCR demonstrates high concordance with results from invasive fungal diagnostic tests.
  • These findings support curtailing high-risk invasive specimen collection in immunocompromised patients suspected of IMD.

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