Plasma Microbial Cell-Free DNA Sequencing in Immunocompromised Patients With Pneumonia : A Prospective Observational Study
© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America..
BACKGROUND: Pneumonia is a common cause of morbidity and mortality, yet a causative pathogen is identified in a minority of cases. Plasma microbial cell-free DNA sequencing may improve diagnostic yield in immunocompromised patients with pneumonia.
METHODS: In this prospective, multicenter, observational study of immunocompromised adults undergoing bronchoscopy to establish a pneumonia etiology, plasma microbial cell-free DNA sequencing was compared to standardized usual care testing. Pneumonia etiology was adjudicated by a blinded independent committee. The primary outcome, additive diagnostic value, was assessed in the Per Protocol population (patients with complete testing results and no major protocol deviations) and defined as the percent of patients with an etiology of pneumonia exclusively identified by plasma microbial cell-free DNA sequencing. Clinical additive diagnostic value was assessed in the Per Protocol subgroup with negative usual care testing.
RESULTS: Of 257 patients, 173 met Per Protocol criteria. A pneumonia etiology was identified by usual care in 52/173 (30.1%), plasma microbial cell-free DNA sequencing in 49/173 (28.3%) and the combination of both in 73/173 (42.2%) patients. Plasma microbial cell-free DNA sequencing exclusively identified an etiology of pneumonia in 21/173 patients (additive diagnostic value 12.1%, 95% confidence interval [CI], 7.7% to 18.0%, P < .001). In the Per Protocol subgroup with negative usual care testing, plasma microbial cell-free DNA sequencing identified a pneumonia etiology in 21/121 patients (clinical additive diagnostic value 17.4%, 95% CI, 11.1% to 25.3%).
CONCLUSIONS: Non-invasive plasma microbial cell-free DNA sequencing significantly increased diagnostic yield in immunocompromised patients with pneumonia undergoing bronchoscopy and extensive microbiologic and molecular testing.
CLINICAL TRIALS REGISTRATION: NCT04047719.
| Errataetall: |
CommentIn: Clin Infect Dis. 2024 Mar 20;78(3):785-787. - PMID 37795586 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:78 |
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| Enthalten in: |
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America - 78(2024), 3 vom: 20. März, Seite 775-784 |
| Sprache: |
Englisch |
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| Links: |
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| Anmerkungen: |
Date Completed 22.03.2024 Date Revised 29.03.2024 published: Print ClinicalTrials.gov: NCT04047719 CommentIn: Clin Infect Dis. 2024 Mar 20;78(3):785-787. - PMID 37795586 Citation Status MEDLINE |
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| doi: |
10.1093/cid/ciad599 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Plasma Microbial Cell-Free DNA Sequencing in Immunocompromised Patients With Pneumonia |b A Prospective Observational Study |
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| 500 | |a Date Revised 29.03.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a ClinicalTrials.gov: NCT04047719 | ||
| 500 | |a CommentIn: Clin Infect Dis. 2024 Mar 20;78(3):785-787. - PMID 37795586 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. | ||
| 520 | |a BACKGROUND: Pneumonia is a common cause of morbidity and mortality, yet a causative pathogen is identified in a minority of cases. Plasma microbial cell-free DNA sequencing may improve diagnostic yield in immunocompromised patients with pneumonia | ||
| 520 | |a METHODS: In this prospective, multicenter, observational study of immunocompromised adults undergoing bronchoscopy to establish a pneumonia etiology, plasma microbial cell-free DNA sequencing was compared to standardized usual care testing. Pneumonia etiology was adjudicated by a blinded independent committee. The primary outcome, additive diagnostic value, was assessed in the Per Protocol population (patients with complete testing results and no major protocol deviations) and defined as the percent of patients with an etiology of pneumonia exclusively identified by plasma microbial cell-free DNA sequencing. Clinical additive diagnostic value was assessed in the Per Protocol subgroup with negative usual care testing | ||
| 520 | |a RESULTS: Of 257 patients, 173 met Per Protocol criteria. A pneumonia etiology was identified by usual care in 52/173 (30.1%), plasma microbial cell-free DNA sequencing in 49/173 (28.3%) and the combination of both in 73/173 (42.2%) patients. Plasma microbial cell-free DNA sequencing exclusively identified an etiology of pneumonia in 21/173 patients (additive diagnostic value 12.1%, 95% confidence interval [CI], 7.7% to 18.0%, P < .001). In the Per Protocol subgroup with negative usual care testing, plasma microbial cell-free DNA sequencing identified a pneumonia etiology in 21/121 patients (clinical additive diagnostic value 17.4%, 95% CI, 11.1% to 25.3%) | ||
| 520 | |a CONCLUSIONS: Non-invasive plasma microbial cell-free DNA sequencing significantly increased diagnostic yield in immunocompromised patients with pneumonia undergoing bronchoscopy and extensive microbiologic and molecular testing | ||
| 520 | |a CLINICAL TRIALS REGISTRATION: NCT04047719 | ||
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| 650 | 4 | |a hematopoietic cell transplant | |
| 650 | 4 | |a immunocompromised pneumonia | |
| 650 | 4 | |a microbial cell-free DNA sequencing | |
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