This study reveals the real-life impact of viral multiplex rtPCR in both children and adults, which was more limited in adults but improved when results were seen in the context of biomarkers, radiology, and antibiotic pre-treatment. As substantial reduction of unnecessary antibiotic prescriptions seems possible, it will be necessary to develop more structured management algorithms incorporating molecular diagnostics including bacterial pathogens, which need to be prospectively tested in their efficacy and safety in RTI.