Clinical Application and Evaluation of Metagenomic Next-Generation Sequencing in Pulmonary Infection with Pleural Effusion

Xu, Huifang; Hu, Xiaoman; Wang, Wenyu; Chen, Hong; Yu, Fangfei; Zhang, Xiaofei; Wu, Zheng; Han, Ke

doi:10.2147/idr.s365757

Cited by 9 publications

(17 citation statements)

References 43 publications

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“…Although many studies have evaluated the performance of mNGS in different types of infections, most of these studies are limited to a single type of sample and may lead to biased conclusions if generalized to a broader scale of clinical infectious disease. 18 , 19 Therefore, this study aimed to address this gap and analyze the practical clinical efficacy of mNGS in a large comprehensive tertiary hospital. A total of 518 patients suspected of infection were eventually included in this study.…”

Section: Discussionmentioning

confidence: 99%

Clinical Efficacy and Diagnostic Value of Metagenomic Next-Generation Sequencing for Pathogen Detection in Patients with Suspected Infectious Diseases: A Retrospective Study from a Large Tertiary Hospital

Xiao¹,

Liu²,

Wu³

et al. 2023

IDR

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Purpose Metagenomic next-generation sequencing (mNGS) is a powerful yet unbiased method to identify pathogens in suspected infections. However, little is known about its clinical effectiveness. The present study aimed to assess the efficacy of mNGS in routine clinical practice. Patients and Methods In this single-center retrospective cohort study, 518 patients with suspected infectious diseases were assessed for inclusion. Among them, each patient had undergone mNGS testing; 407 patients had undergone both microbial culture and mNGS testing. The result of mNGS testing was compared to microbial culture performed concurrently. The diagnostic performance of mNGS was evaluated using the comprehensive clinical diagnosis as the reference standard. Results There was a significant difference in the positive detection rates of pathogens between mNGS and culture (331/407, 81.3% vs 79/407, 19.4%, P < 0.001). The sensitivity of mNGS was much higher than the culture method (79.5% vs 21.3%, P < 0.001), especially in sample types of sputum and bronchoalveolar lavage fluid (BALF). Notably, the sensitivity of blood mNGS was relatively lower than other sample types (67.4% vs 88.9–93.8%). Pathogen cfDNA load based on standardized stringently mapped read number at the species level of microorganisms (SDSMRN) was significantly lower in blood than in other sample types from the same patient ( P = 0.0003). Importantly, mNGS directly led to a change of treatment regimen in 142 (27.4%) cases, including antibiotic escalation (15.3%), antibiotic de-escalation (9.1%), and early definitive diagnosis to initiate appropriate treatment (3.1%). Conclusion Our in-house mNGS platform significantly improved the sensitivity for the diagnosis of infectious diseases. mNGS has the potential to improve clinical outcomes by optimizing antimicrobial therapy.

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Section: Discussionmentioning

confidence: 99%

Clinical Efficacy and Diagnostic Value of Metagenomic Next-Generation Sequencing for Pathogen Detection in Patients with Suspected Infectious Diseases: A Retrospective Study from a Large Tertiary Hospital

Xiao¹,

Liu²,

Wu³

et al. 2023

IDR

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“…This study design thus aimed to capture a more accurate representation of the diagnostic uncertainty facing clinicians in real-world practice. To our knowledge, only one other study has not used prior knowledge of pleural fluid biochemistry or microbiology for molecular PSI identification and characterisation; their PSI positivity rate was 70% 15 . Lower 'real world' PSI-positive rates suggest that a subset of patients with clinically suspected PSI and/or para-pneumonic effusions have no pleural microbial biomass at time of sampling (38% in this study), even with highly sensitive deep sequencing methodologies.…”

Section: Discussionmentioning

confidence: 99%

“…Patients with culture-positive PSI exhibit more severe disease and higher mortality 3 ; understanding PSI microbiome composition thus plays a critically important role in improving patient prognosis. Recent work 7,8,14,15 has highlighted the potential advantages of applying culture-independent molecular methods in PSI diagnostics. To this end, we performed a pragmatic, single-centre, prospective study of individuals with clinician-suspected PSI to better understand the comparative diagnostic yield and clinical value of culture-independent technologies.…”

Section: Discussionmentioning

confidence: 99%

“…Several recent studies applying culture-independent techniques have revealed improved diagnostic yield, and a previously untapped PSI microbiome, confirming that, in many cases, PSI is a polymicrobial disease with a diverse range of co-aggregating pathogens 7,8,14,15 . Complex symbiotic interactions and cross-talk between and among microbes may therefore play an important role in PSI development, natural history, response to treatment, and prognosis 8 .…”

Section: Introductionmentioning

confidence: 90%

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Evaluating the feasibility, sensitivity, and specificity of next-generation molecular methods for pleural infection diagnosis

Bell,

Baird,

Goddard

et al. 2023

Preprint

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Pleural space infections (PSIs) are common and associated with substantial healthcare cost, morbidity, and mortality. Accurate PSI diagnosis remains challenging due to low culture positivity rates, frequent polymicrobial involvement, and non-specific diagnostic biomarkers. To better understand the comparative diagnostic yield of culture-independent technologies for PSI diagnosis, we prospectively characterised 26 clinically suspected PSIs and 10 control patients with non-infective pleural effusions using shotgun metagenomics, bacterial metataxonomics, quantitative PCR, and conventional culture. We demonstrate that culture-independent molecular techniques have superior sensitivity and negative predictive values for PSI diagnosis compared with conventional culture. Bacterial metataxonomics and metagenomics were both sensitive to the detection of polymicrobial infections, and unveiled microbial heterogeneity. Metagenomics also detected fungi and DNA viruses within pleural fluid. Dominant pathogens in the PSI cohort according to the highest resolution method, metagenomics, included streptococci (S. intermedius,S. pyogenes,S. mitis),Prevotellaspp. (P. oris,P. pleuritidis), staphylococci (S. aureus,S. saprophyticus), andKlebsiella pneumoniae. Taken together, these results demonstrate the potential utility of molecular methods in the accurate diagnosis of PSI, which represents an important step towards improving personalised treatment decision-making and antimicrobial stewardship in suspected PSI.

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“…Pleural effusions are mainly built up by host inflammation reactions. Another reason is the incidence of pleural infection is limited (approximately 8 cases per 100,000 people), and pulmonary infections occasionally induce peripheral pulmonary lesions by common Gram-positive and Gram-negative bacteria [ 28 ]. The PPV of pleural fluid in mycobacteria detection is higher because of the high incidences of tuberculous pleurisy in our hospital.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of respiratory samples in etiology diagnosis and microbiome characterization by metagenomic sequencing

et al. 2022

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Background The application of clinical mNGS for diagnosing respiratory infections improves etiology diagnosis, however at the same time, it brings new challenges as an unbiased sequencing method informing all identified microbiomes in the specimen. Methods Strategy evaluation and metagenomic analysis were performed for the mNGS data generated between March 2017 and October 2019. Diagnostic strengths of four specimen types were assessed to pinpoint the more appropriate type for mNGS diagnosis of respiratory infections. Microbiome complexity was revealed between patient cohorts and infection types. A bioinformatic pipeline resembling diagnosis results was built based upon multiple bioinformatic parameters. Results The positive predictive values (PPVs) for mNGS diagnosing of non-mycobacterium, Nontuberculous Mycobacteria (NTM), and Aspergillus were obviously higher in bronchoalveolar lavage fluid (BALF) demonstrating the potency of BALF in mNGS diagnosis. Lung tissues and sputum were acceptable for diagnosis of the Mycobacterium tuberculosis (MTB) infections. Interestingly, significant taxonomy differences were identified in sufficient BALF specimens, and unique bacteriome and virome compositions were found in the BALF specimens of tumor patients. Our pipeline showed comparative diagnostic strength with the clinical microbiological diagnosis. Conclusions To achieve reliable mNGS diagnosis result, BALF specimens for suspicious common infections, and lung tissues and sputum for doubtful MTB infections are recommended to avoid the false results given by the complexed respiratory microbiomes. Our developed bioinformatic pipeline successful helps mNGS data interpretation and reduces manual corrections for etiology diagnosis.

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Clinical Application and Evaluation of Metagenomic Next-Generation Sequencing in Pulmonary Infection with Pleural Effusion

Cited by 9 publications

References 43 publications

Clinical Efficacy and Diagnostic Value of Metagenomic Next-Generation Sequencing for Pathogen Detection in Patients with Suspected Infectious Diseases: A Retrospective Study from a Large Tertiary Hospital

Clinical Efficacy and Diagnostic Value of Metagenomic Next-Generation Sequencing for Pathogen Detection in Patients with Suspected Infectious Diseases: A Retrospective Study from a Large Tertiary Hospital

Evaluating the feasibility, sensitivity, and specificity of next-generation molecular methods for pleural infection diagnosis

Evaluation of respiratory samples in etiology diagnosis and microbiome characterization by metagenomic sequencing

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