Establishing the etiology of respiratory tract infections (RTI) is often difficult due to the lack of a diagnostic gold standard and the inability to detect the causative pathogen. A large proportion of RTI is believed to be caused by respiratory viruses [1–6]. With widespread availability of molecular methods such as multiplex real-time polymerase chain reaction (rtPCR), clinical workflow has changed dramatically and the sensitivity of viral diagnostics has increased remarkably compared to conventional methods [3, 7–13]. However, the significance of virus detection remains unclear as the presence of a virus does not prove causality. Many respiratory viruses can be carried by asymptomatic children [4, 6, 14] and can be shed over prolonged periods, thus discrimination between carriage and infection is challenging [13–15]. Viral infection was reported previously to predispose to bacterial super-infection and concerns about possible bacterial co-infection remain [3, 7–13, 16–19]. Ruling out a bacterial infection with traditional microbiological techniques is frequently impossible [1, 5]. The predictive value of clinical signs to differentiate between viral and bacterial infection is also low [13, 17, 20–22]. On these grounds, clinical management of patients after respiratory virus diagnosis is controversial and surprisingly poorly studied. Overall, extensive yet often unnecessary use of antibiotics in RTI is common [1, 5, 6]. This adult and pediatric retrospective cohort study analyzed whether identification of a virus by multiplex rtPCR was associated with changes in the antibiotic treatment.