Novel point-of-care biomarker combination tests to differentiate acute bacterial from viral respiratory tract infections to guide antibiotic prescribing: a systematic review.

ABSTRACT

BACKGROUND: Acute respiratory tract infections (RTIs) are the most common reason to seek medical care, with many patients receiving inappropriate antibiotics. Novel testing approaches to identify aetiology at the point-of-care are required to accurately guide antibiotic treatment. OBJECTIVE: To assess the diagnostic accuracy of biomarker combinations to rapidly differentiate between acute bacterial or viral RTI aetiology. DATA SOURCES MEDLINE, Embase and Web of Science databases were searched to February 2021. STUDY ELIGIBILITY CRITERIA Diagnostic accuracy studies comparing accuracy of point-of-care and rapid diagnostic tests in primary or secondary care, consisting of biomarker combinations, to identify bacterial or viral aetiology of RTI. METHODS: Risk of bias was assessed using the QUADAS-2 tool. Sensitivity and specificity of tests reported by more than one study were meta-analysed using a random effects model. RESULTS: Twenty observational studies (3514 patients) were identified. Eighteen were judged at high risk of bias. For bacterial aetiologies, sensitivity ranged from 61% to 100% and specificity from 18% to 96%. For viral aetiologies, sensitivity ranged from 59% to 97% and specificity from 74% to 100%. Studies evaluating two commercial tests were meta-analysed. For ImmunoXpert, the summary sensitivity and specificity were 85% (95% CI 75%-91%, k = 4) and 86% (95% CI 73%-93%, k = 4) for bacterial infections, and 90% (95% CI 79%-96%, k = 3) and 92% (95% CI 83%-96%, k = 3) for viral infections, respectively. FebriDx had pooled sensitivity and specificity of 84% (95% CI 75%-90%, k = 4) and 93% (95% CI 90%-95%, k = 4) for bacterial infections, and 87% (95% CI 72%-95%; k = 4) and 82% (95% CI 66%-86%, k = 4) for viral infections, respectively. CONCLUSION: Combinations of biomarkers show potential clinical utility in discriminating the aetiology of RTIs. However, the limitations in the evidence base, due to a high proportion of studies with high risk of bias, preclude firm conclusions. Future research should be in primary care and evaluate patient outcomes and cost-effectiveness with experimental study designs. CLINICAL TRIAL PROSPERO registration number CRD42020178973.