Host Genomic Biomarkers Can Distinguish Bacterial from Non-Bacterial Infection
A systematic review and meta-analysis of 72 studies evaluating 116 host-derived genomic biomarkers in over 16,000 patients found pooled sensitivity of 80% and specificity of 86% for diagnosing bacterial infection. While these transcriptomic and genomic signatures show significant clinical potential as rapid diagnostics to reduce inappropriate antibiotic use, further validation and platform development are needed before routine implementation.
The original study
Systematic review of host genomic biomarkers of invasive bacterial disease: Distinguishing bacterial from non-bacterial causes of acute febrile illness.
- Authors
- Kelly E, Whelan SO, Harriss E, Murphy S, Pollard AJ, O' Connor D
- Journal
- EBioMedicine
- Type
- Journal Article, Meta-Analysis, Systematic Review
- PMID
- 35792524
Original abstract
BACKGROUND: Infectious diseases play a significant role in the global burden of disease. The gold standard for the diagnosis of bacterial infection, bacterial culture, can lead to diagnostic delays and inappropriate antibiotic use. The advent of high- throughput technologies has led to the discovery of host-based genomic biomarkers of infection, capable of differentiating bacterial from other causes of infection, but few have achieved validation for use in a clinical setting. METHODS: A systematic review was performed. PubMed/Ovid Medline, Ovid Embase and Scopus databases were searched for relevant studies from inception up to 30/03/2022 with forward and backward citation searching of key references. Studies assessing the diagnostic performance of human host genomic biomarkers of bacterial infection were included. Study selection and assessment of quality were conducted by two independent reviewers. A meta-analysis was undertaken using a diagnostic random-effects model. The review was registered with PROSPERO (ID: CRD42021208462). FINDINGS: Seventy-two studies evaluating the performance of 116 biomarkers in 16,216 patients were included. Forty-six studies examined TB-specific biomarker performance and twenty-four studies assessed biomarker performance in a paediatric population. The results of pooled sensitivity, specificity, negative and positive likelihood ratio, and diagnostic odds ratio of genomic biomarkers of bacterial infection were 0.80 (95% CI 0.78 to 0.82), 0.86 (95% CI 0.84 to 0.88), 0.18 (95% CI 0.16 to 0.21), 5.5 (95% CI 4.9 to 6.3), 30.1 (95% CI 24 to 37), respectively. Significant between-study heterogeneity (I2 77%) was present. INTERPRETATION: Host derived genomic biomarkers show significant potential for clinical use as diagnostic tests of bacterial infection however, further validation and attention to test platform is warranted before clinical implementation can be achieved. FUNDING: No funding received.