The clinical utility of bronchoalveolar lavage fluid metagenomic next-generation sequencing in immunocompromised critically ill patients with invasive pulmonary aspergillosis: a multicenter retrospective study

ABSTRACT The clinical utility of metagenomic next-generation sequencing (mNGS) in immunocompromised critically ill patients with invasive pulmonary aspergillosis (IPA) remains poorly studied. Given the diagnostic challenges and high mortality associated with IPA in this population, further research...

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Main Authors: Junjie Zhao, Runxi Zhuge, Kai Guo, Jing Tang, Yong Sun, Yi Zhang, Lingmin Yuan, Canhu Qiu, Youqin Yan, Kaiyu Wang, Qin Jiang, Juan Chen, Zhidan Hua, Liyan Qiu, Honglong Fang, Jiancheng Zhuge
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Language:English
Published: American Society for Microbiology 2025-08-01
Series:Microbiology Spectrum
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Online Access:https://journals.asm.org/doi/10.1128/spectrum.00584-25
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author Junjie Zhao
Runxi Zhuge
Kai Guo
Jing Tang
Yong Sun
Yi Zhang
Lingmin Yuan
Canhu Qiu
Youqin Yan
Kaiyu Wang
Qin Jiang
Juan Chen
Zhidan Hua
Liyan Qiu
Honglong Fang
Jiancheng Zhuge
author_facet Junjie Zhao
Runxi Zhuge
Kai Guo
Jing Tang
Yong Sun
Yi Zhang
Lingmin Yuan
Canhu Qiu
Youqin Yan
Kaiyu Wang
Qin Jiang
Juan Chen
Zhidan Hua
Liyan Qiu
Honglong Fang
Jiancheng Zhuge
author_sort Junjie Zhao
collection DOAJ
description ABSTRACT The clinical utility of metagenomic next-generation sequencing (mNGS) in immunocompromised critically ill patients with invasive pulmonary aspergillosis (IPA) remains poorly studied. Given the diagnostic challenges and high mortality associated with IPA in this population, further research on the use of mNGS for early diagnosis and targeted therapy is urgently needed. This multicenter, retrospective, observational study enrolled immunocompromised patients admitted to the intensive care units of six tertiary hospitals in China from April 2021 to November 2024. Comprehensive clinical data were systematically collected, including demographic information, underlying conditions, and detailed records of specimen types and microbiological examination methods. The primary objective was to evaluate the diagnostic and prognostic values of mNGS in comparison to conventional microbiological tests (CMTs) for IPA in this high-risk population. Kappa analysis results indicated a significant agreement between the results of mNGS and CMTs in both groups (Kappa value = 0.638, P < 0.001). The receiver operating curve demonstrated that mNGS exhibited comparable sensitivity (94.03% vs. 95.52%) and higher specificity (96.20% vs. 78.85%), as well as a higher area under the curve (AUC) (0.951 vs. 0.872) in diagnosing IPA compared to CMTs. Moreover, mNGS was significantly superior to other single methods, including cultures (AUC: 0.620, sensitivity: 27.88%, specificity: 96.15%), galactomannan test (AUC: 0.711, sensitivity: 53.73%, specificity: 88.46%), and PCR (AUC: 0.770, sensitivity: 62.69%, specificity: 91.35%). The clinical application of mNGS-guided antibiotic adjustments significantly decreased the 28-day mortality rate (46.51% vs. 66.67%, P < 0.05). mNGS is a feasible and highly sensitive diagnostic tool for detecting Aspergillus infections in immunocompromised critically ill patients compared to CMTs and other single conventional methods. It also performs well in identifying mixed infections, facilitating appropriate antibiotic regimen adjustments and improving patient prognosis.IMPORTANCEmNGS demonstrated significantly higher specificity and area under the curve for diagnosing IPA in immunocompromised critically ill patients compared to CMTs. mNGS showed superior diagnostic performance over single methods, such as cultures, galactomannan test, and PCR, with higher sensitivity and specificity for Aspergillus detection. The use of mNGS-guided antibiotic adjustments led to a significant reduction in 28-day mortality (46.51% vs. 66.67%) among immunocompromised patients. mNGS demonstrated utility in identifying mixed infections, supporting targeted therapy and better patient outcomes. The application of mNGS in diagnosing IPA and guiding treatment in ICU patients helped optimize antibiotic regimens, ultimately improving clinical prognosis.
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spelling doaj-art-21d62a61b81b4e2a94e30e73d289f67e2025-08-20T03:43:58ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972025-08-0113810.1128/spectrum.00584-25The clinical utility of bronchoalveolar lavage fluid metagenomic next-generation sequencing in immunocompromised critically ill patients with invasive pulmonary aspergillosis: a multicenter retrospective studyJunjie Zhao0Runxi Zhuge1Kai Guo2Jing Tang3Yong Sun4Yi Zhang5Lingmin Yuan6Canhu Qiu7Youqin Yan8Kaiyu Wang9Qin Jiang10Juan Chen11Zhidan Hua12Liyan Qiu13Honglong Fang14Jiancheng Zhuge15Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaShanghai Medical College, Fudan University, Shanghai, ChinaZhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaZhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaZhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaDepartment of Critical Care Medicine, QuZhou KeCheng People’s Hospital, Quzhou, Zhejiang, ChinaDepartment of Critical Care Medicine, Longyou County People’s Hospital, Quzhou, Zhejiang, ChinaDepartment of Critical Care Medicine, Jiangshan People’s Hospital, Quzhou, Zhejiang, ChinaDepartment of Critical Care Medicine, People’s Hospital of Changshan County, Quzhou, Zhejiang, ChinaDepartment of Critical Care Medicine, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou, Zhejiang, ChinaNursing Department, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Clinical Laboratory, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou, Zhejiang, ChinaPlmonary and Critical Care Medicine, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou, Zhejiang, ChinaQuzhou TCM Hospital at the Junction of Four Provinces Affiliated to Zhejiang Chinese Medical University, Quzhou, Zhejiang, ChinaDepartment of Critical Care Medicine, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou, Zhejiang, ChinaQuzhou TCM Hospital at the Junction of Four Provinces Affiliated to Zhejiang Chinese Medical University, Quzhou, Zhejiang, ChinaABSTRACT The clinical utility of metagenomic next-generation sequencing (mNGS) in immunocompromised critically ill patients with invasive pulmonary aspergillosis (IPA) remains poorly studied. Given the diagnostic challenges and high mortality associated with IPA in this population, further research on the use of mNGS for early diagnosis and targeted therapy is urgently needed. This multicenter, retrospective, observational study enrolled immunocompromised patients admitted to the intensive care units of six tertiary hospitals in China from April 2021 to November 2024. Comprehensive clinical data were systematically collected, including demographic information, underlying conditions, and detailed records of specimen types and microbiological examination methods. The primary objective was to evaluate the diagnostic and prognostic values of mNGS in comparison to conventional microbiological tests (CMTs) for IPA in this high-risk population. Kappa analysis results indicated a significant agreement between the results of mNGS and CMTs in both groups (Kappa value = 0.638, P < 0.001). The receiver operating curve demonstrated that mNGS exhibited comparable sensitivity (94.03% vs. 95.52%) and higher specificity (96.20% vs. 78.85%), as well as a higher area under the curve (AUC) (0.951 vs. 0.872) in diagnosing IPA compared to CMTs. Moreover, mNGS was significantly superior to other single methods, including cultures (AUC: 0.620, sensitivity: 27.88%, specificity: 96.15%), galactomannan test (AUC: 0.711, sensitivity: 53.73%, specificity: 88.46%), and PCR (AUC: 0.770, sensitivity: 62.69%, specificity: 91.35%). The clinical application of mNGS-guided antibiotic adjustments significantly decreased the 28-day mortality rate (46.51% vs. 66.67%, P < 0.05). mNGS is a feasible and highly sensitive diagnostic tool for detecting Aspergillus infections in immunocompromised critically ill patients compared to CMTs and other single conventional methods. It also performs well in identifying mixed infections, facilitating appropriate antibiotic regimen adjustments and improving patient prognosis.IMPORTANCEmNGS demonstrated significantly higher specificity and area under the curve for diagnosing IPA in immunocompromised critically ill patients compared to CMTs. mNGS showed superior diagnostic performance over single methods, such as cultures, galactomannan test, and PCR, with higher sensitivity and specificity for Aspergillus detection. The use of mNGS-guided antibiotic adjustments led to a significant reduction in 28-day mortality (46.51% vs. 66.67%) among immunocompromised patients. mNGS demonstrated utility in identifying mixed infections, supporting targeted therapy and better patient outcomes. The application of mNGS in diagnosing IPA and guiding treatment in ICU patients helped optimize antibiotic regimens, ultimately improving clinical prognosis.https://journals.asm.org/doi/10.1128/spectrum.00584-25etiologyimmunocompromised patientsbronchoalveolar lavage fluidinvasive pulmonary aspergillosismetagenomic next-generation sequencing
spellingShingle Junjie Zhao
Runxi Zhuge
Kai Guo
Jing Tang
Yong Sun
Yi Zhang
Lingmin Yuan
Canhu Qiu
Youqin Yan
Kaiyu Wang
Qin Jiang
Juan Chen
Zhidan Hua
Liyan Qiu
Honglong Fang
Jiancheng Zhuge
The clinical utility of bronchoalveolar lavage fluid metagenomic next-generation sequencing in immunocompromised critically ill patients with invasive pulmonary aspergillosis: a multicenter retrospective study
Microbiology Spectrum
etiology
immunocompromised patients
bronchoalveolar lavage fluid
invasive pulmonary aspergillosis
metagenomic next-generation sequencing
title The clinical utility of bronchoalveolar lavage fluid metagenomic next-generation sequencing in immunocompromised critically ill patients with invasive pulmonary aspergillosis: a multicenter retrospective study
title_full The clinical utility of bronchoalveolar lavage fluid metagenomic next-generation sequencing in immunocompromised critically ill patients with invasive pulmonary aspergillosis: a multicenter retrospective study
title_fullStr The clinical utility of bronchoalveolar lavage fluid metagenomic next-generation sequencing in immunocompromised critically ill patients with invasive pulmonary aspergillosis: a multicenter retrospective study
title_full_unstemmed The clinical utility of bronchoalveolar lavage fluid metagenomic next-generation sequencing in immunocompromised critically ill patients with invasive pulmonary aspergillosis: a multicenter retrospective study
title_short The clinical utility of bronchoalveolar lavage fluid metagenomic next-generation sequencing in immunocompromised critically ill patients with invasive pulmonary aspergillosis: a multicenter retrospective study
title_sort clinical utility of bronchoalveolar lavage fluid metagenomic next generation sequencing in immunocompromised critically ill patients with invasive pulmonary aspergillosis a multicenter retrospective study
topic etiology
immunocompromised patients
bronchoalveolar lavage fluid
invasive pulmonary aspergillosis
metagenomic next-generation sequencing
url https://journals.asm.org/doi/10.1128/spectrum.00584-25
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