BACKGROUND: Noninvasive diagnostic options are limited for invasive mold infections (IMIs). We evaluated the performance of a plasma microbial cell-free DNA sequencing (mcfDNA-Seq) test for diagnosing pulmonary IMI after hematopoietic cell transplant (HCT). METHODS: We retrospectively assessed the diagnostic performance of plasma mcfDNA-Seq next-generation sequencing in 114 HCT recipients with pneumonia after HCT who had stored plasma obtained within 14 days of diagnosis of proven/probable Aspergillus IMI (n = 51), proven/probable non-Aspergillus IMI (n = 24), possible IMI (n = 20), and non-IMI controls (n = 19). Sequences were aligned to a database including >400 fungi. Organisms above a fixed significance threshold were reported. RESULTS: Among 75 patients with proven/probable pulmonary IMI, mcfDNA-Seq detected ≥1 pathogenic mold in 38 patients (sensitivity, 51% [95% confidence interval {CI}, 39%-62%]). When restricted to samples obtained within 3 days of diagnosis, sensitivity increased to 61%. McfDNA-Seq had higher sensitivity for proven/probable non-Aspergillus IMI (sensitivity, 79% [95% CI, 56%-93%]) compared with Aspergillus IMI (sensitivity, 31% [95% CI, 19%-46%]). McfDNA-Seq also identified non-Aspergillus molds in an additional 7 patients in the Aspergillus subgroup and Aspergillus in 1 patient with possible IMI. Among 19 non-IMI pneumonia controls, mcfDNA-Seq was negative in all samples, suggesting a high specificity (95% CI, 82%-100%) and up to 100% positive predictive value (PPV) with estimated negative predictive values (NPVs) of 81%-99%. The mcfDNA-Seq assay was complementary to serum galactomannan index testing; in combination, they were positive in 84% of individuals with proven/probable pulmonary IMI. CONCLUSIONS: Noninvasive mcfDNA-Seq had moderate sensitivity and high specificity, NPV, and PPV for pulmonary IMI after HCT, particularly for non-Aspergillus species.
BACKGROUND: Noninvasive diagnostic options are limited for invasive mold infections (IMIs). We evaluated the performance of a plasma microbial cell-free DNA sequencing (mcfDNA-Seq) test for diagnosing pulmonary IMI after hematopoietic cell transplant (HCT). METHODS: We retrospectively assessed the diagnostic performance of plasma mcfDNA-Seq next-generation sequencing in 114 HCT recipients with pneumonia after HCT who had stored plasma obtained within 14 days of diagnosis of proven/probable Aspergillus IMI (n = 51), proven/probable non-Aspergillus IMI (n = 24), possible IMI (n = 20), and non-IMI controls (n = 19). Sequences were aligned to a database including >400 fungi. Organisms above a fixed significance threshold were reported. RESULTS: Among 75 patients with proven/probable pulmonary IMI, mcfDNA-Seq detected ≥1 pathogenic mold in 38 patients (sensitivity, 51% [95% confidence interval {CI}, 39%-62%]). When restricted to samples obtained within 3 days of diagnosis, sensitivity increased to 61%. McfDNA-Seq had higher sensitivity for proven/probable non-Aspergillus IMI (sensitivity, 79% [95% CI, 56%-93%]) compared with Aspergillus IMI (sensitivity, 31% [95% CI, 19%-46%]). McfDNA-Seq also identified non-Aspergillus molds in an additional 7 patients in the Aspergillus subgroup and Aspergillus in 1 patient with possible IMI. Among 19 non-IMI pneumonia controls, mcfDNA-Seq was negative in all samples, suggesting a high specificity (95% CI, 82%-100%) and up to 100% positive predictive value (PPV) with estimated negative predictive values (NPVs) of 81%-99%. The mcfDNA-Seq assay was complementary to serum galactomannan index testing; in combination, they were positive in 84% of individuals with proven/probable pulmonary IMI. CONCLUSIONS: Noninvasive mcfDNA-Seq had moderate sensitivity and high specificity, NPV, and PPV for pulmonary IMI after HCT, particularly for non-Aspergillus species.
Authors: Timothy A Blauwkamp; Simone Thair; Judith C Wilber; Samuel Yang; Michael J Rosen; Lily Blair; Martin S Lindner; Igor D Vilfan; Trupti Kawli; Fred C Christians; Shivkumar Venkatasubrahmanyam; Gregory D Wall; Anita Cheung; Zoë N Rogers; Galit Meshulam-Simon; Liza Huijse; Sanjeev Balakrishnan; James V Quinn; Desiree Hollemon; David K Hong; Marla Lay Vaughn; Mickey Kertesz; Sivan Bercovici Journal: Nat Microbiol Date: 2019-02-11 Impact factor: 17.745
Authors: J Springer; M Lackner; D Nachbaur; M Girschikofsky; B Risslegger; W Mutschlechner; J Fritz; W J Heinz; H Einsele; A J Ullmann; J Löffler; C Lass-Flörl Journal: Clin Microbiol Infect Date: 2015-09-21 Impact factor: 8.067
Authors: Chadi A Hage; Eva M Carmona; Oleg Epelbaum; Scott E Evans; Luke M Gabe; Qusay Haydour; Kenneth S Knox; Jay K Kolls; M Hassan Murad; Nancy L Wengenack; Andrew H Limper Journal: Am J Respir Crit Care Med Date: 2019-09-01 Impact factor: 21.405
Authors: Min Xu; Xuan Qin; Michael L Astion; Joe C Rutledge; Joanne Simpson; Keith R Jerome; Janet A Englund; Danielle M Zerr; Russell T Migita; Shannon Rich; John C Childs; Anne Cent; Mark A Del Beccaro Journal: Am J Clin Pathol Date: 2013-01 Impact factor: 2.493
Authors: Guang-Shing Cheng; Zach J Stednick; David K Madtes; Michael Boeckh; George B McDonald; Steven A Pergam Journal: Biol Blood Marrow Transplant Date: 2016-08-31 Impact factor: 5.742