Host-response biomarker MxA for etiological discrimination of pediatric lower respiratory tract infections: implications for diagnostic study design.

Background and Objective: Accurate differentiation between viral and bacterial etiologies remains a major clinical challenge in pediatric lower respiratory tract infections (LRTIs), often leading to unnecessary antibiotic use. Host-response biomarkers such as myxovirus resistance protein A (MxA) reflect interferon-mediated antiviral responses and offer a biologically grounded diagnostic approach. This review aims to synthesize current evidence on the diagnostic performance of MxA in pediatric LRTIs and to derive methodological insights for the design of future prospective diagnostic studies. Methods: A structured narrative review was conducted, integrating evidence from pediatric studies evaluating MxA across viral, bacterial, and mixed infections, with emphasis on study design features, reference standards, and biomarker performance. Results: MxA is consistently elevated in viral infections and demonstrates superior discriminatory performance compared with conventional inflammatory markers such as C-reactive protein (CRP) and procalcitonin (PCT). In contrast, MxA remains low in most isolated bacterial infections, reflecting limited interferon activation. However, its performance declines in mixed infections, where intermediate expression patterns reduce classification accuracy. Combined biomarker strategies (e.g., MxA-CRP) improve discrimination by integrating complementary host-response signals. Conclusions: MxA is a promising host-response biomarker for pediatric LRTI. Future studies should incorporate standardized etiological definitions, explicitly defined mixed infection subgroups, age-specific reference ranges, and multi-marker strategies within pragmatic clinical pathways to enable clinical translation and optimize antibiotic stewardship.