Employing Viruses to Treat Bacterial Infections

Innovations in Pulmonology, Critical Care & Sleep Medicine | Winter 2024

Bronchiectasis is a specific type of damage to airways in the lungs caused by a variety of conditions other than cystic fibrosis (CF). Damaged airways tend to accumulate mucus, which predisposes people with bronchiectasis to lung infections that the immune system cannot totally eliminate.

Alex Gifford, MD, FCCP

That combination of mucus build-up, infection and inflammation causes even more lung damage. At University Hospitals Cleveland Medical Center, Alex Gifford, MD, FCCP, is studying a novel approach to treat adults with bronchiectasis not caused by CF, also called non-CF bronchiectasis.

Non-CF bronchiectasis historically has been underdiagnosed because symptoms are not specific and are sometimes attributed to other lung problems, like asthma, chronic obstructive pulmonary disease (COPD) and/or pneumonia. Widespread use of computed tomography (CT or CAT) scans to screen for lung cancer and evaluate health problems in the emergency department has increased the number of people diagnosed with bronchiectasis.

Citing reports in the medical literature, Dr. Gifford says that there are 350,000 to 500,000 cases of non-CF bronchiectasis in the U.S. and that the condition is more common in women and older adults.

Pseudomonas Aeruginosa: A Formidable Threat

Pseudomonas aeruginosa (P. aeruginosa) is a species of bacteria found in natural and man-made environments that can infect the lungs of people with non-CF bronchiectasis. P. aeruginosa enters the lungs when a person inhales water vapor created by showers, hot tubs, saunas and natural water sources. The fact that P. aeruginosa exists so widely is a major reason it’s harmful to people with non-CF bronchiectasis.

“Once Pseudomonas gains a foothold in the lungs of patients with bronchiectasis, it can adapt to the airway environment and evade the immune system,” Dr. Gifford says. “Pseudomonas is also notoriously capable of becoming resistant to antibiotics, limiting treatment options, so the discovery of new therapies is always necessary. At UH, we’re participating in a new clinical trial focused on that goal.”

Tailwind Trial

“This phase 2 study, called Tailwind [Study to Evaluate the Safety, Phage Kinetics, and Efficacy of Inhaled AP-PA02 in Subjects With Non-Cystic Fibrosis Bronchiectasis and Chronic Pulmonary Pseudomonas aeruginosa Infection (ClinicalTrials.gov ID NCT05616221)], takes advantage of the fact that, in nature, there are viruses called bacteriophages that might be harnessed to fight bacterial infections,” Dr. Gifford says. “This is an attractive strategy to fight infections because bacteriophages specifically kill bacteria and leave human cells alone.”

Bacteriophages designed to kill P. aeruginosa were recently studied in people with bronchiectasis caused by CF who had this type of bacterial infection (SWARM-P.a.; ClinicalTrials.gov ID NCT04596319).

“Positive results from SWARM-P.a. support the conduct of Tailwind in people with non-CF bronchiectasis,” Dr. Gifford says.

According to Dr. Gifford, Tailwind is enrolling “adults with non-CF bronchiectasis demonstrated by chest CT scan with evidence of P. aeruginosa infection within 24 months of screening.” He further states that participants are allowed to have moderately decreased lung function, but cannot be severely malnourished, have a history of solid organ transplant or a diagnosis of immunodeficiency.

The Tailwind study design involves the use of placebo control because bacteriophages are not part of the standard of care for people with non-CF bronchiectasis. There are two recruiting arms; one arm includes participants who have not used inhaled antibiotics to treat P. aeruginosa infection. A second arm includes participants who have used inhaled antibiotics for at least three months to treat P. aeruginosa infection.

“The primary objective of Tailwind is to evaluate the efficacy, safety and distribution properties of the inhaled AP-PA02 bacteriophage product,” Dr. Gifford says. “The hypothesis is that AP-PA02 will significantly reduce the number of P. aeruginosa bacteria in sputum samples collected after a pre-treatment baseline sample.”

Dr. Gifford says the study has a few additional exploratory outcomes, including measuring changes in lung function from baseline, changes in breathing symptoms from baseline and assessing other chemical aspects of patients' sputum samples.

Looking Ahead

Typically, if the results of a phase 2 clinical trial like Tailwind are promising, the next step in development is a phase 3 clinical trial designed to confirm safety and efficacy of a drug candidate in a larger group of patients, and sometimes to compare the effects of a drug candidate to existing therapies. 

“The adult pulmonary division at UH is participating in this study because it supports our institutional mission and allows us to potentially help a group of patients whose health is always compromised to some extent,” Dr. Gifford says. “We’re fighting an infection that can overcome antibiotics, so we need new options. Although Tailwind is a multicenter trial, UH is the only participating academic institution in our region.”

For more information about the Tailwind trial, contact Jennie Pexa, RN, Research Manager for the Division of Pulmonary, Critical Care, & Sleep Medicine at 216-844-2381 or Dr. Gifford at 216-286-7415.

Contributing Expert:
Alex Gifford, MD, FCCP
Pulmonary and Critical Care
University Hospitals Cleveland Medical Center
University Hospitals Rainbow Babies & Children’s Hospital
Associate Professor of Medicine and Pediatrics
Case Western Reserve University School of Medicine