A Host-Response Assay Distinguishes Between Simple Influenza Patients And Influenza Patients With Bacterial Coinfection

Background Identifying bacterial coinfection in influenza patients can be difficult as the symptoms of simple influenza versus mixed infections are often similar, leading to antibiotic overuse. A new host-response assay (ImmunoXpert™) that integrates the levels of three proteins (TRAIL, IP-10, and CRP) was shown to exhibit high performance in distinguishing between bacterial and viral disease in two double-blind validation studies. Here we sought to evaluate its ability to differentiate between simple influenza and influenza with bacterial coinfection. Material/Methods The study population included 653 febrile pediatric and adult patients prospectively recruited in the ‘Curiosity’ study. Patient etiology (simple viral versus mixed infection) was determined by unanimous expert adjudication based on comprehensive clinical, laboratory and radiological assessment. Influenza strains (A or B) were detected using multiplex PCR applied to nasal swabs (Seeplex-RV15). We compared the expert panel diagnosis with the assay that gives three possible outcomes: viral, bacterial (including viral with bacterial coinfection) or equivocal. An equivocal outcome does not provide diagnostic information and is observed in ∼10% of cases. Results Out of 653 patients, 51 had positive influenza detection and unanimous expert diagnosis: 44 simple viral infections and 7 influenza with bacterial coinfections (Figure 1). Antibiotics were prescribed to all 7 cases of influenza with bacterial coinfection and to 20/44 cases adjudicated as simple viral infections, indicating an overuse rate of 45%. The assay correctly classified 40 of the 44 simple viral cases (out of the remaining 4, 2 were assigned viral with bacterial coinfection and 2 received equivocal outcomes) as well as 5 of the 7 viral with bacterial coinfection cases (the remaining 2 received equivocal outcomes) supporting the assay’s potential to reduce antibiotic overuse 5-fold (from 45% to 4/44=9%, P Conclusion The host-response assay can differentiate between simple influenza and influenza patients with bacterial coinfection, with potential to reduce antibiotic overuse. Utility studies are warranted to demonstrate that the assay can safely assist physicians in correct management of influenza patients