The Avisa BreathTest

The Avisa BreathTest (ABT) is a simple, quantitative, point-of-care test for rapidly detecting pulmonary infections due to certain virulent pathogens without the need to collect and culture sputum or other biological samples. The ABT is intended for use in pediatric and adult pneumonia patients. The test is based on the presence of the urease enzyme found in certain bacterial species that cause pneumonia, such as S. aureus, P. aeruginosa, Klebsiella, Acinetobacter, and H. influenza. Urease activity can be detected using inhaled, nebulized 13C-urea which is converted by these bacteria to labeled carbon dioxide (13CO2) and ammonia. The non-radioactive, isotopic ratio of 13CO2 to naturally occurring 12CO2 is measured in the exhaled breath and large differences in this isotopic ratio (δ13CO2) indicate an active pulmonary infection with a urease pathogen. In combination with clinical signs and symptoms, the ABT will aid clinical decision making as to use and choice of antibiotics for patients diagnosed with pneumonia in the Emergency Department and for Intensive Care Unit (ICU) patients on mechanical ventilation at risk for or suspected of having ventilator associated respiratory infections.

The anticipated value of the ABT is the decreased use of powerful, broad spectrum antibiotics in the Emergency Department and corresponding decrease in hospital admissions because of its high negative predictive value for certain urease bacterial pneumonias.  In addition, the ABT will find application in ventilated patients for early detection of and antibiotic decision guidance for ventilator associated respiratory infections to decrease length of stay, morbidity and mortality.

Previous Clinical Study

Cystic Fibrosis (CF): In 2014 Avisa collaborated withUniversity of New Mexico (UNM) to conduct a proof-of-concept study in human subjects to determine whether inhalation of 13C-urea can be safely used to detect the presence of urease producing bacteria in the lungs. The study cohort consisted of three subjects with cystic fibrosis and known to be colonized with P. aeruginosa but otherwise healthy and three healthy control subjects. The study subjects were administered 20 mg and 50 mg doses of 13C-urea on different days via a jet nebulizer and the resulting exhaled δ13CO2 (DOB) was measured at 5, 10 and 15 minutes after completion of the nebulized dose. Both doses of the nebulized 13C-urea were well tolerated by all study subjects and there were no adverse events. As shown in the figure to the right, the CF subjects colonized with P. aeruginosa had significantly higher DOB levels than the controls at both the 5 and 10 minute breath collection time points and the 50 mg dose of 13C-urea produced better separation between the groups. The exponential decay of the DOB signal suggested that breath collection at time points early than 5 minutes might yield even greater separation between the groups. Details of this study can be found in a recent journal article (H. Raissy, G. Timmins, L Davies, T. Heynekamp, M. Harkins, Z. Sharp, H. W. Kelly, A Proof of Concept Study to Detect Urease Producing Bacteria in Lungs Using Aerosolized 13C Urea. Pediatric Allergy, Immunology, and Pulmonary, 29:68-73, 2016).

Current Clinical Studies

Pneumonia in the Emergency Department (PED): An investigator sponsored clinical of the Avisa BreathTest to detect urease pathogens in patients diagnosed with pneumonia in the Emergency Department is currently enrolling patients at the  University of New Mexico Medical Center Emergency Department as the lead clinical site and a second site at Henry Ford Hospital in Detroit. This trial will provide critical information for planning the pivotal clinical trial for the detection of urease pathogens in patients diagnosed with pneumonia in the Emergency Department, the ABT’s first indication for use.

Chronic Obstructive Pulmonary Disease (COPD): The purpose of this study was to evaluate urease activity in the oral cavity of current and former smokers with COPD, and test its utility as a biomarker for chronic daily respiratory symptoms. The results of this study provide background on oral cavity urease activity in stable COPD subjects and found that COPD subjects that were former smokers had higher levels of urease activity than COPD subjects that still smoke and healthy controls. The study was presented at the 2018 annual American Thoracic Society conference.

A follow-on study is planned to examine urease activity in both the oral cavity and lung of stable COPD subjects and those with exacerbations.

Planned Clinical Studies

Ventilator Associated Pneumonia (VAP): Avisa is planning a pilot study of the ABT’s ability to detect and monitor urease pathogens in 40 mechanically ventilated ICU subjects who are suspected of having a lower respiratory tract infection. The primary study endpoint is the safety and feasibility of performing the ABT in mechanically ventilated patients with a suspected lower respiratory tract infection.  This trial is expected to inform additional studies of the ABT in mechanically ventilated subjects who are at risk for developing lower respiratory tract infections while in the hospital.

Clostridium Difficile (C. Diff)Avisa recently received a U.S Patent for use of the ABT platform technology for detection and monitoring of C. difficile infections using ingested 13C-tyrosine as the drug substrate instead of 13C-urea. Avisa is developing study plans to test the safety and efficacy of our C. difficile test in a series of in-vivo and human studies.

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