A prospective, multi-centre US clinical trial to determine accuracy of FebriDx point-of-care testing for acute upper respiratory infections with and without a confirmed fever

Abstract

Background: FebriDx is a 10-minute disposable point-of-care test designed to identify clinically significant systemic host immune responses and aid in the differentiation of bacterial and viral respiratory infection by simultaneously detecting C-reactive protein (CRP) and myxovirus resistance protein A (MxA) from a fingerstick blood sample. FebriDx diagnostic accuracy was evaluated in the emergency room and urgent care setting.

Methods: A prospective, multicentre, observational cohort study of acute upper respiratory tract infections (URIs), with and without a confirmed fever at the time of enrolment, was performed to evaluate the diagnostic accuracy of FebriDx to identify clinically significant bacterial infection with host response and acute pathogenic viral infection. The reference method consisted of an algorithm with physician override that included bacterial cell culture, respiratory PCR panels for viral and atypical pathogens, procalcitonin, and white blood cell count.

Results: Among 220 patients enrolled, 100% reported fever 100.5°F within the last 72 hours while 55% had a measured hyperthermia (T > 100.4) at the time of enrolment. FebriDx demonstrated a sensitivity of 95% (95% CI: 77–100%), specificity of 94% (88–98%), PPV of 76% (59–87%), and a NPV of 99% (93–100%).

Conclusion: FebriDx may identify clinically significant bacterial URI’s and supports outpatient antibiotic decisions.

Key messages

• FebriDx is an outpatient POC test designed to identify a clinically significant systemic host immune response and aid in the differentiation of viral and bacterial infection through rapid measurement of MxA and CRP from a fingerstick blood sample. FebriDx test was determined to be an accurate test, with a 85% sensitivity, 93% specificity and 97% NPV to rule out bacterial infection for any patient presenting with symptoms and reported fever within the prior 3 days, and when confirming fever (hyperthermia) at the time of testing, the test was even more sensitive (95%) and specific (94%) with a 99% NPV. FebriDx may support antibiotic stewardship by rapidly identifying clinically significant bacterial URIs.

Keywords:

• FebriDx
• MxA
• CRP
• point-of-care
• URI
• diagnostics
• antibiotic stewardship

Acknowledgements

We would like to warmly thank then following people for their tremendous help during this study and manuscript preparation: Jennifer Kasper, Adrienne Baughman, Itegbemie Obaitan, Jasmine Gale, Guruprasad Jambaulikar, Nivedita Patkar, and Paige Farely.

Disclosure statement

The authors received research funding from RPS Diagnostics to conduct this study. Dr. Shapiro reports serving as a paid consultant for Baxter and Cytovale and has received funding from Siemen’s diagnostics and LAjolla pharmaceuticals. Dr. Self reports serving as a paid consultant for Ferring Pharmaceuticals, Cempra Pharmaceuticals, BioTest AG, and Abbott Point of Care. Dr. Hou has served as a paid consultant for Cheetah Medical. Dr. Kurz has received honoraria from Zoll Medical Corporation, and has received research funding from Zoll Medical Corporation and Boehringer-Ingelheim. Dr. Sambursky is an executive at RPS Diagnostics that receives a salary and owns stock options.

Additional information

Funding

This work was supported by RPS Diagnostics, the maker of FebriDx. None of the clinical investigators have any financial interest in RPS Diagnostics. Dr. Sambursky has a financial interest in the company as described above.