Diagnostic value of metagenomic next-generation sequencing of bronchoalveolar lavage fluid for the diagnosis of suspected pneumonia in immunocompromised patients

Lin, Pengcheng; Chen, Yi; Su, Shanshan; Nan, Wengang; Zhou, Lingping; Zhou, Ying; Li, Yuping

doi:10.1186/s12879-022-07381-8

Cited by 24 publications

(22 citation statements)

References 30 publications

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“…In our study, it has been possible to lyse Aspergillus and extract the relevant DNA for amplification detection well, benefiting from the development of pretreatment techniques for mNGS. A related study by Lin et al, which included 69 immunodeficient patients with suspected pneumonia, concluded in agreement with us that the diagnostic efficacy of mNGS was significantly better than that of CMTs (Lin et al, 2022). Both studies by Peng et al and Lin et al compared the sensitivity and specificity of the two methods through simple statistical calculations, without using statistical tools such as ROC curves to comprehensively analyze the difference in diagnostic efficacy between mNGS and CMTs, and did not give diagnostic cutoff values.…”

Section: Discussionsupporting

confidence: 83%

“…In our study, it has been possible to lyse Aspergillus and extract the relevant DNA for amplification detection well, benefiting from the development of pre-treatment techniques for mNGS. A related study by Lin et al., which included 69 immunodeficient patients with suspected pneumonia, concluded in agreement with us that the diagnostic efficacy of mNGS was significantly better than that of CMTs ( Lin et al., 2022 ). Both studies by Peng et al.…”

Section: Discussionsupporting

confidence: 79%

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Application of metagenomic next-generation sequencing in the diagnosis of pulmonary invasive fungal disease

Wang

You²,

Fu³

et al. 2022

Front. Cell. Infect. Microbiol.

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BackgroundMetagenomic next-generation sequencing (mNGS) is increasingly being used to detect pathogens directly from clinical specimens. However, the optimal application of mNGS and subsequent result interpretation can be challenging. In addition, studies reporting the use of mNGS for the diagnosis of invasive fungal infections (IFIs) are rare.ObjectiveWe critically evaluated the performance of mNGS in the diagnosis of pulmonary IFIs, by conducting a multicenter retrospective analysis. The methodological strengths of mNGS were recognized, and diagnostic cutoffs were determined.MethodsA total of 310 patients with suspected pulmonary IFIs were included in this study. Conventional microbiological tests (CMTs) and mNGS were performed in parallel on the same set of samples. Receiver operating characteristic (ROC) curves were used to evaluate the performance of the logarithm of reads per kilobase per million mapped reads [lg(RPKM)], and read counts were used to predict true-positive pathogens.ResultThe majority of the selected patients (86.5%) were immunocompromised. Twenty species of fungi were detected by mNGS, which was more than was achieved with standard culture methods. Peripheral blood lymphocyte and monocyte counts, as well as serum albumin levels, were significantly negatively correlated with fungal infection. In contrast, C-reactive protein and procalcitonin levels showed a significant positive correlation with fungal infection. ROC curves showed that mNGS [and especially lg(RPKM)] was superior to CMTs in its diagnostic performance. The area under the ROC curve value obtained for lg(RPKM) in the bronchoalveolar lavage fluid of patients with suspected pulmonary IFIs, used to predict true-positive pathogens, was 0.967, and the cutoff value calculated from the Youden index was −5.44.ConclusionsIn this study, we have evaluated the performance of mNGS-specific indicators that can identify pathogens in patients with IFIs more accurately and rapidly than CMTs, which will have important clinical implications.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionsupporting

confidence: 79%

Application of metagenomic next-generation sequencing in the diagnosis of pulmonary invasive fungal disease

Wang

You²,

Fu³

et al. 2022

Front. Cell. Infect. Microbiol.

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“…In fact, nowadays, PCP has a fair proportion in the non-HIV immunocompromised children. The rapid detection of pathogens by mNGS is conducive to the timely diagnosis and treatment of critically pediatric patients [33][34][35]. In this retrospective study of 17 PCP critically pediatric patients, the dominant underlying conditions included hematologic malignancies, solid tumors, and rheumatic diseases.…”

Section: Discussionmentioning

confidence: 99%

Metagenomic next-generation sequencing for the diagnosis of Pneumocystis jirovecii Pneumonia in critically pediatric patients

Chen

Liang

Wang

et al. 2023

Ann Clin Microbiol Antimicrob

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Objective The aim of this study was to evaluate the effectiveness of metagenomic next-generation sequencing (mNGS) for the diagnosis of Pneumocystis jirovecii Pneumonia (PCP) in critically pediatric patients. Methods Seventeen critically pediatric patients with PCP and sixty patients diagnosed with non-PCP pneumonia who were admitted in pediatric intensive care unit between June 2018 and July 2021 were enrolled. Conventional methods and mNGS for detecting Pneumocystis jirovecii (P. jirovecii) were compared. The patients’ demographics, comorbidities, laboratory test results, antibiotic treatment response and 30 day mortality were analyzed. Result The mNGS showed a satisfying diagnostic performance with a sensitivity of 100% in detecting P. jirovecii compared with Gomori methenamine silver staining (5.9%), serum (1,3)-β-D-glucan (86.7%) and and LDH (55.6%). The diagnostic specificity of mNGS for PCP was higher than that of serum BDG (56.7%) and LDH (71.4%). In PCP group, over one thirds’ cases had mixed infections. Compared with survivors, non-survivors had higher stringently mapped read numbers (SMRNs) in bronchoalveolar lavage fluid (BALF) sample (P < 0.05), suggesting SMRNs were closely associated with the severity of response. The detection for P. jirovecii by mNGS both in BALF and blood samples reached a concordance rate of 100%, and the SMRNs in the BALF were remarkably higher than that in blood samples. Initial antimicrobial treatment was modified in 88.2% of PCP patients based on the mNGS results. Conclusion The mNGS is a potential and efficient technology in diagnosing PCP and shows a satisfying performance in the detection of co-pathogens. Both blood and BALF samples for mNGS are suggested for the presumptive diagnosis of PCP.

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“…Unfortunately, our study was not further validated using Gomori methenamine silver staining, which may have influenced the comparison of the two testing methods. Recent studies ( Wang et al., 2019b ; Lin et al., 2022 ) have shown that mNGS has good diagnostic performance in the detection of pneumocystis. The identification of Aspergillus spp.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic value of bronchoalveolar lavage fluid metagenomic next-generation sequencing in pediatric pneumonia

Deng¹,

Wu³

et al. 2022

Front. Cell. Infect. Microbiol.

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ObjectivesThe aim of this study was to evaluate the diagnostic value of bronchoalveolar lavage fluid (BALF) metagenomic next-generation sequencing (mNGS) versus conventional microbiological tests (CMTs) for pediatric pneumonia.MethodsThis retrospective observational study enrolled 103 children who were diagnosed with pneumonia and hospitalized at Hubei Maternity and Child Health Care Hospital between 15 October 2020 and 15 February 2022. The pneumonia diagnosis was based on clinical manifestations, lung imaging, and microbiological tests. Pathogens in the lower respiratory tract were detected using CMTs and BALF mNGS (of DNA and RNA). The diagnostic performance of BALF mNGS was compared with that of CMTs.ResultsIn 96 patients, pathogens were identified by microbiological tests. The overall pathogen detection rate of mNGS was significantly higher than that of CMTs (91.3% vs. 59.2%, p = 0.000). The diagnostic performance of mNGS varied for different pathogens; however, its sensitivity and accuracy for diagnosing bacterial and viral infections were both higher than those of CMTs (p = 0.000). For the diagnosis of fungi, the sensitivity of mNGS (87.5%) was higher than that of CMTs (25%); however, its specificity and accuracy were lower than those of CMTs (p < 0.01). For the diagnosis of Mycoplasma pneumoniae, the specificity (98.8%) and accuracy (88.3%) of mNGS were high; however, its sensitivity (42.1%) was significantly lower than that of CMTs (100%) (p = 0.001). In 96 patients with definite pathogens, 52 cases (50.5%) were infected with a single pathogen, while 44 cases (42.7%) had polymicrobial infections. Virus–bacteria and virus–virus co-infections were the most common. Staphylococcus aureus, Haemophilus influenzae, rhinovirus, cytomegalovirus, parainfluenza virus, and fungi were more likely to be associated with polymicrobial infections.ConclusionsBALF mNGS improved the detection rate of pediatric pneumonia, especially in mixed infections. The diagnostic performance of BALF mNGS varies according to pathogen type. mNGS can be used to supplement CMTs. A combination of mNGS and CMTs may be the best diagnostic strategy.

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Diagnostic value of metagenomic next-generation sequencing of bronchoalveolar lavage fluid for the diagnosis of suspected pneumonia in immunocompromised patients

Cited by 24 publications

References 30 publications

Application of metagenomic next-generation sequencing in the diagnosis of pulmonary invasive fungal disease

Application of metagenomic next-generation sequencing in the diagnosis of pulmonary invasive fungal disease

Metagenomic next-generation sequencing for the diagnosis of Pneumocystis jirovecii Pneumonia in critically pediatric patients

Diagnostic value of bronchoalveolar lavage fluid metagenomic next-generation sequencing in pediatric pneumonia

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