Dataset Information

Bacterial and Viral Respiratory Tract Microbiota and Host Characteristics in Adults With Lower Respiratory Tract Infections: A Case-Control Study.

ABSTRACT:

Background

Viruses and bacteria from the nasopharynx are capable of causing community-acquired pneumonia (CAP), which can be difficult to diagnose. We aimed to investigate whether shifts in the composition of these nasopharyngeal microbial communities can be used as diagnostic biomarkers for CAP in adults.

Methods

We collected nasopharyngeal swabs from adult CAP patients and controls without infection in a prospective multicenter case-control study design. We generated bacterial and viral profiles using 16S ribosomal RNA gene sequencing and multiplex polymerase chain reaction (PCR), respectively. Bacterial, viral, and clinical data were subsequently used as inputs for extremely randomized trees classification models aiming to distinguish subjects with CAP from healthy controls.

Results

We enrolled 117 cases and 48 control subjects. Cases displayed significant beta diversity differences in nasopharyngeal microbiota (P = .016, R2 = .01) compared to healthy controls. Our extremely randomized trees classification models accurately discriminated CAP caused by bacteria (area under the curve [AUC] .83), viruses (AUC .95) or mixed origin (AUC .81) from healthy control subjects. We validated this approach using a dataset of nasopharyngeal samples from 140 influenza patients and 38 controls, which yielded highly accurate (AUC .93) separation between cases and controls.

Conclusions

Relative proportions of different bacteria and viruses in the nasopharynx can be leveraged to diagnose CAP and identify etiologic agent(s) in adult patients. Such data can inform the development of a microbiota-based diagnostic panel used to identify CAP patients and causative agents from nasopharyngeal samples, potentially improving diagnostic specificity, efficiency, and antimicrobial stewardship practices.

SUBMITTER: Haak BW

PROVIDER: S-EPMC8906706 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Publications

Bacterial and Viral Respiratory Tract Microbiota and Host Characteristics in Adults With Lower Respiratory Tract Infections: A Case-Control Study.

Haak Bastiaan W BW Brands Xanthe X Davids Mark M Peters-Sengers Hessel H Kullberg Robert F J RFJ van Houdt Robin R Hugenholtz Floor F Faber Daniël R DR Zaaijer Hans L HL Scicluna Brendon P BP van der Poll Tom T Joost Wiersinga W W

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20220301 5

<h4>Background</h4>Viruses and bacteria from the nasopharynx are capable of causing community-acquired pneumonia (CAP), which can be difficult to diagnose. We aimed to investigate whether shifts in the composition of these nasopharyngeal microbial communities can be used as diagnostic biomarkers for CAP in adults.<h4>Methods</h4>We collected nasopharyngeal swabs from adult CAP patients and controls without infection in a prospective multicenter case-control study design. We generated bacterial a ...[more]

PMID: 34156449

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Project description:BackgroundLower respiratory tract infections (LRTIs) are a leading cause of childhood morbidity and mortality. Potentially pathogenic organisms are present in the respiratory tract in both symptomatic and asymptomatic children, but their presence does not necessarily indicate disease. We aimed to assess the concordance between upper and lower respiratory tract microbiota during LRTIs and the use of nasopharyngeal microbiota to discriminate LRTIs from health.MethodsFirst, we did a prospective study of children aged between 4 weeks and 5 years who were admitted to the paediatric intensive care unit (PICU) at Wilhelmina Children's Hospital (Utrecht, Netherlands) for a WHO-defined LRTI requiring mechanical ventilation. We obtained paired nasopharyngeal swabs and deep endotracheal aspirates from these participants (the so-called PICU cohort) between Sept 10, 2013, and Sept 4, 2016. We also did a matched case-control study (1:2) with the same inclusion criteria in children with LRTIs at three Dutch teaching hospitals and in age-matched, sex-matched, and time-matched healthy children recruited from the community. Nasopharyngeal samples were obtained at admission for cases and during home visits for controls. Data for child characteristics were obtained by questionnaires and from pharmacy printouts and medical charts. We used quantitative PCR and 16S rRNA-based sequencing to establish viral and bacterial microbiota profiles, respectively. We did sparse random forest classifier analyses on the bacterial data, viral data, metadata, and the combination of all three datasets to distinguish cases from controls.Findings29 patients were enrolled in the PICU cohort. Intra-individual concordance in terms of viral microbiota profiles (96% agreement [95% CI 93-99]) and bacterial microbiota profiles (58 taxa with a median Pearson's r 0·93 [IQR 0·62-0·99]; p<0·05 for all 58 taxa) was high between nasopharyngeal and endotracheal aspirate samples, supporting the use of nasopharyngeal samples as proxy for lung microbiota during LRTIs. 154 cases and 307 matched controls were prospectively recruited to our case-control cohort. Individually, bacterial microbiota (area under the curve 0·77), viral microbiota (0·70), and child characteristics (0·80) poorly distinguished health from disease. However, a classification model based on combined bacterial and viral microbiota plus child characteristics distinguished children with LRTIs from their matched controls with a high degree of accuracy (area under the curve 0·92).InterpretationOur data suggest that the nasopharyngeal microbiota can serve as a valid proxy for lower respiratory tract microbiota in childhood LRTIs, that clinical LRTIs in children result from the interplay between microbiota and host characteristics, rather than a single microorganism, and that microbiota-based diagnostics could improve future diagnostic and treatment protocols.FundingSpaarne Gasthuis, University Medical Center Utrecht, and the Netherlands Organization for Scientific Research.

Project description:Lower respiratory tract infections (LRTIs) remain a significant global cause of infectious disease-related mortality. Accurate discrimination between acute bacterial and viral LRTIs is crucial for optimal patient care, prevention of unnecessary antibiotic prescriptions, and resource allocation. Plasma samples from LRTI patients with bacterial (n = 36), viral (n = 27; excluding SARS-CoV-2), SARS-CoV-2 (n = 22), and mixed bacterial-viral (n = 38) etiology were analyzed for protein profiling. Whole-blood RNA samples from a subset of patients (bacterial, n = 8; viral, n = 8; and SARS-CoV-2, n = 8) were analyzed for transcriptional profiling. Lasso regression modeling identified a seven-protein signature (CRP, IL4, IL9, IP10, MIP1α, MIP1β, and TNFα) that discriminated between patients with bacterial (n = 36) vs viral (n = 27) infections with an area under the curve (AUC) of 0.98. When comparing patients with bacterial and mixed bacterial-viral infections (antibiotics clinically justified; n = 74) vs patients with viral and SARS-CoV-2 infections (antibiotics clinically not justified; n = 49), a 10-protein signature (CRP, bFGF, eotaxin, IFNγ, IL1β, IL7, IP10, MIP1α, MIP1β, and TNFα) with an AUC of 0.94 was identified. The transcriptional profiling analysis identified 232 differentially expressed genes distinguishing bacterial (n = 8) from viral and SARS-CoV-2 (n = 16) etiology. Protein-protein interaction enrichment analysis identified 20 genes that could be useful in the differentiation between bacterial and viral infections. Finally, we examined the performance of selected published gene signatures for bacterial-viral differentiation in our gene set, yielding promising results. Further validation of both protein and gene signatures in diverse clinical settings is warranted to establish their potential to guide the treatment of acute LRTIs.ImportanceAccurate differentiation between bacterial and viral lower respiratory tract infections (LRTIs) is vital for effective patient care and resource allocation. This study investigated specific protein signatures and gene expression patterns in plasma and blood samples from LRTI patients that distinguished bacterial and viral infections. The identified signatures can inform the design of point-of-care tests that can aid healthcare providers in making informed decisions about antibiotic prescriptions in order to reduce unnecessary use, thereby contributing to reduced side effects and antibiotic resistance. Furthermore, the potential for faster and more accurate diagnoses for improved patient management in acute LRTIs is compelling.

Dataset Information

Bacterial and Viral Respiratory Tract Microbiota and Host Characteristics in Adults With Lower Respiratory Tract Infections: A Case-Control Study.

Background

Methods

Results

Conclusions

Publications

Bacterial and Viral Respiratory Tract Microbiota and Host Characteristics in Adults With Lower Respiratory Tract Infections: A Case-Control Study.

Similar Datasets

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