A Host-response Assay Distinguishes Between Simple Influenza Patients and Influenza Patients with Bacterial Coinfection

רנאא דאמוני שלבי 2 Meital Paz 1 Kfir Oved 1 Tanya Gottlieb 1 Asi Cohen 1 Roy Navon 1 Niv Mastboim 1 Ellen Bamberger 1,2,3 Tom Friedman 1,4 Liat Etshtein 1,4 Olga Boico 1 Irina Chistyakov 2,3 Adi Klein 3,5 Israel Potasman 6 FIDSA . 3,6 Eran Eden 1 Liran Shani 1 Isaac Srugo 2,3
1MeMed Diagnostics, Tirat Carmel, Haifa, Israel
2Department of Pediatrics, Bnai-Zion Medical Center, Haifa, Israel
3Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
4Rambam, Health Care Campus, Haifa, Israel
5Department of Pediatrics, Hillel Yaffe Medical Center, Hadera, Israel
6Infectious Diseases, Bnai Zion Medical Center, Haifa, Israel

Background:
Identifying bacterial coinfection in influenza patients is challenging. A new host-response assay (ImmunoXpert™) that integrates the levels of three proteins (TRAIL/IP-10/CRP) exhibited high performance in distinguishing bacterial from viral disease. We sought to evaluate its ability to differentiate between simple influenza and influenza with bacterial coinfection.

Material/Methods:
The study population included 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 was 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.

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). The assay correctly classified 40 of the 44 simple viral cases as well as 5 of the 7 viral with bacterial coinfection cases. 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 has the potential to reduce antibiotic overuse 5-fold (from 45% to 4/44=9%, P<0.001).

Figure 1

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.









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