Metagenomic Study in Parapneumonic Effusion

NCT05394220 | Recruiting

• 1 other identifier: PPE_Metagenomic
• Study Type: observational
• Target: 115
• Locations: 1 country
• Sites: 1

Brief Summary

Objective: To identify known and unknown bacterial pathogens in patients with pleural infections using a combination of conventional culture and next-generation sequencing approaches. Hypothesis to be tested: The investigators hypothesize that next-generation sequencing will serve as a comprehensive approach to identify culturable and unculturable bacterial pathogens in patients with pleural infections compared to the conventional culture. Design and subjects: This is a prospective cohort study to be conducted in the medical department of a tertiary care hospital in Hong Kong involving patients with pleural infection. Patients will be recruited if a pleural infection is suspected, with pleural fluid sampled and a 6-month follow-up. The clinical management by the medical team will not be interfered. Study instruments: Pleural fluid will be collected for conventional culture, 16S amplicon and shotgun metagenomic sequencing in parallel. The clinical information will be collected to clarify the causative correlation between symptoms, clinical outcomes and pathogen infections. Main outcome measures: The full spectrum of causative bacteria in pleural infection will be characterized. The diagnostic performance of identifying causative bacteria in pleural infection will be compared between the studied methods. The antimicrobial resistance pattern, clinical outcomes of pleural infection will also be compared between groups as categorized by the pattern of bacteriology identified by different methods. Data analysis: With reference to the conventional culture as the gold standard, sensitivity, specificity, positive predictive values and negative predictive values of 16S ribosomal ribonucleic acid (rRNA) gene amplicon and shotgun metagenomic sequencing will be calculated.

Conditions

Parapneumonic Effusion

Keywords

parapneumonic effusion; pleural infection; metagenomics

Outcome Measures

Primary Outcomes (1)

• Characterize the full spectrum of causative bacteria in pleural infection and compare the diagnostic performance of identifying the pathogens between conventional culture, 16S rRNA gene amplicon and shotgun metagenomic sequencing

  Characterize the full spectrum of causative bacteria in pleural infection and compare the diagnostic performance of identifying the pathogens between conventional culture, 16S rRNA gene amplicon and shotgun metagenomic sequencing

  36 months

Secondary Outcomes (6)

• Compare the agreement rates in detecting causative bacteria between conventional microbiology, 16S rRNA gene amplicon and shotgun metagenomic sequencing

  36 months

• Characterize and compare the antimicrobial resistance patterns of causative bacteria in pleural infections between conventional culture, 16S rRNA gene amplicon sequencing and shotgun metagenomic sequencing

  36 months

• Identify the factors that contributed to negative results using conventional culture in pleural fluid

  36 months

• Compare the clinical course of disease and outcomes in patients with pleural infection based on the molecular sequencing (different types of patterns, if identified) and culture (positive or negative) results

  36 months

• Emergence of infection due to drug-resistant bacteria during the use of broad-spectrum antibiotics

  36 months

Study Arms (2)

Parapneumonic effusion

Patients with parapneumonic effusion

Diagnostic Test: 16S rRNA gene amplicon sequencing

Non-parapneumonic effusion

Patients with pleural effusion but not parapneumonic in nature

Diagnostic Test: 16S rRNA gene amplicon sequencing

Interventions

16S rRNA gene amplicon sequencing DIAGNOSTIC_TEST

molecular sequencing for the microbiome in parapneumonic effusion

Also known as: Shotgun metagenomic sequencing

Non-parapneumonic effusion; Parapneumonic effusion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Study group: patients with parapneumonic effusion Control group: patients with pleural effusion but not parapneumonic in nature

You may qualify if:

• Patients hospitalized for suspected pleural infection, irrespective of community-acquired or hospital-acquired in nature
• Pleural tapping will be performed for pleural fluid analysis
• Chinese ethnicity
• Aged 18 years old or above

You may not qualify if:

• Use of antibiotics for more than 24 hours for the current episode of infection
• On long-term local or systemic antibiotics
• Tuberculous pleuritis
• Pregnant or lactating women
• Failed to obtain informed consent due to patient's refusal or cognitive impairment
• Control group (patients with effusions but not parapneumonic in nature)
• Pleural effusion is not related to any infection including pneumonia (e.g. malignancy, fluid overload)
• Pleural tapping will be performed for pleural fluid analysis
• Chinese ethnicity
• Aged 18 years old or above
• The use of systemic (including oral and intravenous) and inhaled antibiotics in the past 1 month
• On long-term local or systemic antibiotics
• Tuberculous pleuritis
• Pregnant or lactating women
• Failed to obtain informed consent due to patient's refusal or cognitive impairment

Sponsors & Collaborators

• Chinese University of Hong Kong: lead

Study Sites (1)

Chinese University of Hong Kong

Hong Kong, Hong Kong

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Pleural fluid, oral swab and faecal mass obtained from patients with and without pleural infection will be stored for subsequent bacterial microbiota analysis using genetic sequencing techniques

Central Study Contacts

Ka Pang Chan, MBChB

CONTACT

35052211; chankapang@gmail.com

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Doctor (Clinical Lecturer)

Study Record Dates

• First Submitted: May 23, 2022
• First Posted: May 27, 2022
• Study Start: June 1, 2023
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): May 31, 2027
• Last Updated: June 29, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)