NIH Study Will Assess Biomarker as Potential Indicator of Whether Lower Respiratory Tract Infections Improve with Antibacterial Treatment

February 13, 2018

A new clinical trial sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, aims to determine whether low blood levels of the protein procalcitonin can reliably indicate whether a person’s lower respiratory tract infection will improve with antibiotic treatment.

Lower respiratory tract infections (LRTIs) can cause a variety of symptoms, including persistent coughing, wheezing, chest pain, fever, and rapid or difficult breathing. Healthcare providers often prescribe a course of antibiotics as standard treatment without knowing for certain whether an infection is bacterial or viral. Taking antibiotics for viral infections is not only ineffective but can also introduce potential side effects and promote antimicrobial resistance.

Procalcitonin (PCT) is normally produced by the healthy human body in minute quantities, and serves as a precursor to calcitonin, a hormone which helps regulate calcium levels. Currently, medical professionals are able to test patients’ blood for high PCT levels, which are an indicator of bacterial sepsis, a life-threatening complication of infection that triggers inflammation throughout the body. The researchers leading the new clinical trial theorize that low PCT levels in patients with LRTIs may indicate that the infection is viral, not bacterial.

“Healthcare providers and patients benefit from precise diagnostic tests to guide treatment decisions,” said NIAID Director Anthony S. Fauci, M.D. “An effective biomarker for confirming that a lower respiratory tract infection is viral and thus not treatable with antibiotics would be a significant development in our collective efforts to reduce inappropriate use of antibiotics and combat antimicrobial resistance.”

The study is being led by principal investigator Ephraim Tsalik, M.D., Ph.D., associate professor of medicine at Duke University and a physician at the Durham VA Health Care System in Durham, N.C. It will enroll patients 18 years of age or older with suspected LRTIs and low PCT blood levels (0.25 ng/mL or less). The patients’ blood will be tested for PCT levels using bioMérieux’s VIDAS® BRAHMS PCT™ test. After their PCT levels have been confirmed, as many as 420 patients will be randomized to receive either a 5-day regimen of the oral antibiotic azithromycin (500 mg as a single dose on day one followed by 250 mg once daily for four days) or placebo. Patients whose symptoms worsen will be immediately referred for appropriate care. At day five, all the patients will be evaluated for improvement in their symptoms. Additional follow-up with the patients will occur on days 11 and 28 to determine their health status.

If no significant difference in improvement rates between volunteers treated with azithromycin and those receiving placebo is found, this result will suggest that low PCT levels could indeed identify patients who are unlikely to benefit from antibiotic treatment. Conversely, if the volunteers given antibiotics tend to recover faster or better than those given placebo, the results will indicate that low PCT levels are not a reliable biomarker to guide the use of antibiotics for LRTIs.

The study, which is expected to conclude by 2020, was developed by the NIAID-supported Antibacterial Resistance Leadership Group (ARLG) in collaboration with bioMérieux researchers and medical experts. It is being conducted through three NIAID-funded Vaccine and Treatment Evaluation Units and three VA Health Care Systems, with a total of five sites enrolling participants in Georgia, North Carolina and Texas.

For more information about the study, please visit ClinicalTrials.gov using the identifier NCT03341273.