Systematic review of host genomic biomarkers of invasive bacterial disease: Distinguishing bacterial from non-bacterial causes of acute febrile illness

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. Fortysix 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 (I-2 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.. Copyright (C) 2022 The Authors. Published by Elsevier B.V.

Automated summary

This study conducted a systematic review to evaluate the performance of host genomic biomarkers in the diagnosis of bacterial infection. The results showed that host genomic biomarkers have high sensitivity and specificity for bacterial infection, indicating their potential clinical utility, but further validation is needed before clinical implementation.