Dataset Information

Clinical metagenomics assessments improve diagnosis and outcomes in community-acquired pneumonia.

ABSTRACT:

Background

Identifying the causes of community-acquired pneumonia (CAP) is challenging due to the disease's complex etiology and the limitations of traditional microbiological diagnostic methods. Recent advances in next generation sequencing (NGS)-based metagenomics allow pan-pathogen detection in a single assay, and may have significant advantages over culture-based techniques.

Results

We conducted a cohort study of 159 CAP patients to assess the diagnostic performance of a clinical metagenomics assay and its impact on clinical management and patient outcomes. When compared to other techniques, clinical metagenomics detected more pathogens in more CAP cases, and identified a substantial number of polymicrobial infections. Moreover, metagenomics results led to changes in or confirmation of clinical management in 35 of 59 cases; these 35 cases also had significantly improved patient outcomes.

Conclusions

Clinical metagenomics could be a valuable tool for the diagnosis and treatment of CAP.

Trial registration

Trial registration number with the Chinese Clinical Trial Registry: ChiCTR2100043628 .

SUBMITTER: Xie F

PROVIDER: S-EPMC8047593 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Publications

Clinical metagenomics assessments improve diagnosis and outcomes in community-acquired pneumonia.

Xie Fei F Duan Zhimei Z Zeng Weiqi W Xie Shumei S Xie Mingzhou M Fu Han H Ye Qing Q Xu Teng T Xie Lixin L

BMC infectious diseases 20210415 1

<h4>Background</h4>Identifying the causes of community-acquired pneumonia (CAP) is challenging due to the disease's complex etiology and the limitations of traditional microbiological diagnostic methods. Recent advances in next generation sequencing (NGS)-based metagenomics allow pan-pathogen detection in a single assay, and may have significant advantages over culture-based techniques.<h4>Results</h4>We conducted a cohort study of 159 CAP patients to assess the diagnostic performance of a clini ...[more]

PMID: 33858378

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Project description:ObjectiveSevere community-acquired pneumonia (sCAP) is one of the major diseases within the ICU. We hypothesize that subtyping sCAP based on simple inflammatory markers, organ dysfunction, and clinical metagenomics results is feasible.MethodIn this study, we retrospectively enrolled immunocompetent sCAP patients requiring invasive mechanical ventilation, who underwent clinical metagenomics from 17 medical centers. We collected data on potentially pathogenic species reported by clinical metagenomics and clinical information for all patients. Latent class analysis (LCA) was applied to routine clinical parameters such as gender, age, white blood cell (WBC), lymphocytes, C-reactive protein (CRP), and Procalcitonin (PCT), identifying two optimally fitting models.ResultsA total of 569 patients were enrolled. Compared to class B, class A was characterized by a younger age, higher CRP and PCT levels, and a higher incidence of coagulation dysfunction, liver failure, circulatory failure, and renal failure. However, the mortality rates were similar between the two groups. In class A, more cases of Streptococcus spp. and fewer cases of HSV-1 and Candida spp. were detected. Among the patients in the two phenotypes, 48.7% and 57.5% received corticosteroid treatment, respectively. In the class A, corticosteroid treatment was not associated with patient mortality (unadjusted hazard ratio (HR)=0.988; 95% confidence interval (CI), 0.634-1.541; p=0.959). In contrast, in the class B group, the use of corticosteroids was associated with a reduced mortality rate (adjusted HR=0.719; 95% CI, 0.525-0.986; p=0.04). Additional analysis showed that in class B, methylprednisolone was associated with reduced mortality (adjusted HR=0.61; 95% CI, 0.44-0.86; p=0.005), while dexamethasone was not associated with mortality (adjusted HR=1.4; 95% CI, 0.89-2.22; p=0.148). In addition, after dose conversion, the results showed that higher doses of corticosteroids in class B were associated with increased mortality (adjusted HR=1.01; 95% CI, 1.00-1.01; p=0.005).ConclusionWe identified two classes based on clinical metagenomics and clinical features. Class B exhibited a better response to corticosteroid compared to class A. The rapid identification of these phenotypes could facilitate the screening of sCAP patients responsive to corticosteroid in future prospective clinical trials.

Project description:Background Bacterial intestinal communities interact with the immune system and may contribute to protection against community-acquired pneumonia (CAP). Intestinal viruses are closely integrated with these bacterial communities, yet the composition and clinical significance of these communities in CAP patients are unknown. The aims of this exploratory study were to characterise the composition of the rectal bacteriome and virome at hospital admission for CAP, and to determine if microbiota signatures correlate with clinical outcomes. Methods We performed a prospective observational cohort study in CAP patients, admitted to a university or community hospital in the Netherlands between October 2016 and July 2018, and controls. Rectal bacteriome and virome composition were characterised using 16S ribosomal RNA gene sequencing and virus discovery next-generation sequencing, respectively. Unsupervised multi-omics factor analysis was used to assess the co-variation of bacterial and viral communities, which served as primary predictor. The clinical outcomes of interest were the time to clinical stability and the length of hospital stay. Findings 64 patients and 38 controls were analysed. Rectal bacterial alpha (p = 0•0015) and beta diversity (r2 =0•023, p = 0•004) of CAP patients differed from controls. Bacterial and viral microbiota signatures correlated with the time to clinical stability (hazard ratio 0•43, 95% confidence interval 0•20-0•93, p = 0•032) and the length of hospital stay (hazard ratio 0•37, 95% confidence interval 0•17-0•81, p = 0•012), although only the latter remained significant following p-value adjustment for examining multiple candidate cut-points (p = 0•12 and p = 0•046, respectively). Interpretation This exploratory study provides preliminary evidence that intestinal bacteriome and virome signatures could be linked with clinical outcomes in CAP. Such exploratory data, when validated in independent cohorts, could inform the development of a microbiota-based diagnostic panel used to predict clinical outcomes in CAP. Funding Netherlands Organization for Scientific Research and Netherlands Organization for Health Research and Development.

Dataset Information

Clinical metagenomics assessments improve diagnosis and outcomes in community-acquired pneumonia.

Background

Results

Conclusions

Trial registration

Publications

Clinical metagenomics assessments improve diagnosis and outcomes in community-acquired pneumonia.

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