JMIR Publications

ABSTRACT

Background:

Causative pathogens are currently only identified in a minority of cases of pneumonia, with implications for antimicrobial stewardship. Metagenomic next generation sequencing offers promise to improve this, as a sensitive and untargeted approach to identifying pathogens. However, while studies have shown improved sensitivity compared to conventional microbiological methods for pneumonia diagnosis, it remains unclear whether this can translate into clinical benefit. Much existing work has also been performed in ventilated patients, readily allowing for analysis of bronchoalveolar lavage fluid (BALF). The impact of sample type on the utility of metagenomic analysis remains poorly defined. Similarly, previous work has rarely distinguished between the type of pneumonia involved, whether community-acquired (CAP), hospital-acquired (HAP), or ventilator-associated (VAP), despite these having different clinical profiles.

Objective:

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Methods:

We aim to review all studies (excluding case reports of series of less than 10 people) of adult patients with suspected or confirmed pneumonia that compare metagenomic analysis with traditional microbiology techniques, to include culture, antigen-based testing and PCR-based assays. Screening of titles and abstracts, and subsequent review of eligible full texts will be by two separate reviewers, with a third clinician providing adjudication in case of disagreement. Our focus is on the clinical utility of metagenomics for patients with CAP, HAP, and VAP, and data extracted will focus on clinically important outcomes - namely pathogen positivity rate, laboratory turnaround time, impact on clinical decision making, length of stay, and 30-day mortality. Sub-group analysis will be performed based on the type of pneumonia (CAP, HAP or VAP), and sample type used.

Results:

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Conclusions:

Despite significant promise, it is unclear what the likely impact of metagenomic analysis will be on clinical pathways. Further, it is unclear whether the likely utility of this technique will alter depending on whether the pneumonia is a CAP, HAP or VAP or the sample type that is collected. This systematic review will assess the current evidence base to support benefit on clinical outcomes for metagenomic analysis depending on the setting of pneumonia diagnosis, or specimen type used. It will identify areas where further research is needed to advance this methodology into routine care. Clinical Trial: PROSPERO 2023 CRD42023488096 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023488096