Novel Point-of-Care Biomarker Combination Tests to Differentiate Acute Bacterial from Viral Respiratory Tract Infections to Guide Antibiotic Prescribing: A Systematic Review

Henry C Carlton*, Jelena Savović, Sarah Dawson, Philip J Mitchelmore, Martha M C Elwenspoek

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

6 Citations (Scopus)
30 Downloads (Pure)


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.
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.
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.
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.
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.
Original languageEnglish
Pages (from-to)1096-1108
Number of pages13
JournalClinical Microbiology and Infection
Issue number8
Early online date17 May 2021
Publication statusPublished - Aug 2021

Bibliographical note

Funding Information:
HC, SD, PM and ME have nothing to disclose. JS reports grants from NIHR, UK , during the conduct of the study. This research was carried out as part of the undergraduate research project by HC, without any dedicated funding. ME's and JS's time was supported by the National Institute for Health Research Applied Research Collaboration West (NIHR ARC West). The views expressed in this article are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.

Publisher Copyright:
© 2021 The Author(s)


  • antimicrobial resistance
  • diagnostic accuracy
  • point-of-care testing
  • respiratory tract infections
  • systematic review


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