A Molecular Toolkit for the Microbial Investigation of Severe Community Acquired Pneumonia

Imperial College London103 enrolled

Overview

Severe community acquired pneumonia is common and associated with high mortality. Conventional microbiological diagnostics identify pathogens in approximately half of cases, which is inadequate for both clinical and epidemiological purposes. This study applies next-generation sequencing based metagenomic techniques to patients with extremely severe community acquired pneumonia, to investigate the microbiome of severe community acquired pneumonia and evaluate metagenomic approaches as diagnostic tools.

Study Type

OBSERVATIONAL

Enrollment

103

Conditions

Community Acquired Pneumonia Respiration Failure Pneumonia

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Adults aged 18 or over * Admitted to a participating severe respiratory failure centre or ICU * Admitted due to community acquired pneumonia (CAP) according to clinical and radiological criteria * Tracheal intubation, receiving mechanical ventilation +/- ECMO * Requires bronchoscopy as part of routine diagnostic care plan * Bronchoscopy takes place within 72 hours of first admission to hospital Exclusion Criteria: * Any current or previous condition/circumstance that, in the opinion of the investigator or study nurse, may put the individual at risk if participating * Patients receiving end of life care * Hospitalisation within the previous 28 days (not including pre-ECMO hospitalisation for ECMO patients) * Consent or assent not given

Outcomes

Primary Outcomes

Detection of pathogens by metagenomic sequencing applied to bronchoalveolar lavage samples

The proportion of pathogen genome that can be detected in bronchial lavage samples detected by the proportion of the sequenced nucleic acid which is pathogen derived and the proportion of the pathogen genome which be reconstructed.

Time frame: 28 days (From time of enrollment up until end of inclusion)

Secondary Outcomes

Metagenomic detection of pathogen genomes compared to the results of conventional diagnostic techniques

Metagenomic sequencing data obtained will be compared to results obtained from conventional diagnostic tests undertaken as part of the participant's routine clinical care. Data will be used to evaluate the ability of each technique to detect any pathogens found. The conventional microbiological tests that will be used for comparison include those undertaken as part of the participants routine clinical care and will include urinary antigen tests (Pneumococcal and Leigonella); blood, sputum and bronchial lavage culture including polymerase chain reaction (PCR) for Legionella spp, Mycoplasma pneumoniae and Chlamydophila pneumoniae and respiratory viral PCR multiplex assays. The results of serological tests and PCR for Influenza A \&B from nose and throat swabs will also be compared.