Research Into Infections

Infections are a problem for people with cystic fibrosis because they can cause fever, difficulty breathing, coughing, and excessive inflammation. A cycle of recurring infections and inflammation gradually destroys lung tissue.

People with CF are more susceptible to infections from bacteria, viruses, and fungi because abnormally thick, sticky mucus in their lungs traps these germs in the airways. They also are prone to infections because their mucus does not have the same infection-fighting properties as normal mucus. This abnormal mucus provides an ideal environment for bacteria to form protective layers — known as biofilms — that make them more difficult to kill.

To make meaningful progress against this complex challenge, in 2018 we established the five-year Infection Research Initiative to help improve the detection, diagnosis, prevention, and treatment of infections. From 2018 through 2023, we invested more than $170 million to fund research and the development of new treatments. We also conducted a comprehensive review of our research portfolio, identifying and filling gaps, evaluating our investments, and recalibrating our infection research strategy. This initiative helped us set the agenda going forward for a robust infection research program so that we can continue to meet the needs of the CF community.

Chronic infections and drug-resistant bacteria remain key challenges — even for those who take cystic fibrosis transmembrane conductance regulator (CFTR) modulators, such as Trikafta (elexacaftor/tezacaftor/ivacaftor). Therefore, research into infections remains a priority for the CF Foundation. We are continuing to invest in the development of new, innovative therapies to address chronic and difficult-to-treat infections. 

Scientists are researching how germs interact with each other — including how they compete, how they cooperate, and how they affect the strength or degree of damage they can cause to the lungs. Studying these interactions helps researchers develop better strategies to manage and treat infections.

Researchers also are exploring how microorganisms, such as bacteria, respond to the changing environment in the lungs once people start taking modulators and eventually other drugs that target the underlying defect of CF. To assess the impact of the modulator Trikafta on CF infections, the Foundation dedicated a portion of the PROMISE study to increase our understanding of the changes in key bacterial infections in the lung. The PROMISE study is evaluating the overall impact that Trikafta has on people with CF. 

One PROMISE-related study indicates that a minority of people with CF starting Trikafta may be able to clear some bacterial infections from their airways. This did not occur for most people in the study starting Trikafta, but those remaining infected generally had a lower amount of bacteria in their sputum (mucus or phlegm coughed up from the lungs).

Difficult-to-treat infections are another area of focus for researchers. One such example is nontuberculous mycobacteria (NTM). Because a substantial minority of people with CF become infected with NTM, we have funded ongoing research to learn more about these infections. 

We’re supporting researchers who are conducting the PREDICT and PATIENCE studies to create standard ways to diagnose and treat NTM. 

To combat the growing challenge of antibiotic resistance, the Foundation is supporting clinical research into unique treatments that work differently than traditional antibiotics.

• Bacteriophage (phage) therapy is an experimental treatment that uses specialized viruses to kill specific bacterial strains. Currently, people with CF can only access phage treatment in the U.S. through a clinical trial or by using the U.S. Food and Drug Administration compassionate use program, which allows the use of experimental therapies for life-threatening conditions. We are supporting several studies to explore the feasibility of phage therapy as a treatment for drug-resistant infections. For example, the POSTSTAMP study will assess people with CF who receive phage therapy to treat persistent M. abscessus lung disease.
• A majority of chronic infections involve bacteria that have formed biofilms, protective structures that shield bacteria from both the immune system and antibiotics. The Foundation is funding the development of drugs that would disrupt these biofilms, making bacteria more susceptible to antibiotics.
• To grow, bacteria rely on some processes that require iron. If gallium — an atom nearly identical to iron — is taken up by the bacteria instead, it can disrupt these processes and kill the bacteria. The ABATE trial will evaluate IV gallium in people with CF who have NTM. 

In addition to exploring these unique treatments, one of our other strategies is pursuing new drug candidates that can target several types of bacteria at once. This approach might help people with less common — but problematic — bacterial infections where it's harder to develop drugs because of the rarity of these kinds of infections outside CF.

For more information on anti-infectives in development, visit our Drug Development Pipeline or Research We Fund. 

Researchers are exploring when to treat, how long to treat, and what medications to use to fight CF infections. They are especially interested in how best to use antibiotics, so they are most effective.

The STOP 2 trial found that in people with CF who experienced a pulmonary exacerbation, 10 days of IV antibiotic treatment was no worse than 14 days of antibiotic treatment when comparing differences in lung function improvement among those who responded early to treatment. Also, among those slower to respond, 21 days of treatment was not significantly better than 14 days of antibiotic treatment when it comes to lung function improvements.

The STOP-PEDS 2.0 trial will compare the immediate use of oral antibiotics and airway clearance techniques versus just airway clearance techniques to treat pulmonary exacerbations in children with CF. Ultimately, researchers want to determine whether the benefits of starting antibiotics at the first sign of illness outweigh the possible risks, such as side effects and antibiotic resistance. An initial study to test feasibility showed that 70% of participants were able to prevent the use of oral antibiotics.

The STOP 360 trial will compare the improvement of lung function and symptoms in those treated with a single IV antibiotic versus those treated with a similar IV antibiotic plus IV tobramycin — the current standard of care when treating exacerbations caused by Pseudomonas aeruginosa. 

To learn more about current treatments for infections, visit Antibiotics.

It is becoming more difficult for care centers and researchers to test for infections because people with CF are less able to produce sputum while taking CFTR modulators. In addition, it is challenging to obtain sputum samples from children, and some sputum cultures can miss early signs of infection. We are focused on developing alternative diagnostic tests that do not rely on sputum — following up on promising work to use blood, urine, or even breath to determine which infections are present in the lung. 

To enable this research and other opportunities, the Therapeutics Development Network, working with Dr. Gina Hong at the University of Pennsylvania, has launched a new study called SEND-CF that will collect specimens, including breath, blood, and urine samples, from people with CF.

We also are supporting researchers at universities who are working to develop better ways to detect Pseudomonas or NTM lung infections. 
 

People with CF who are on modulators are having fewer exacerbations caused by infections. As a result, researchers have smaller recruitment pools for anti-infective clinical trials. To help address enrollment challenges, we are exploring clinical trials and programs that would include people with CF as well as people who have chronic infections and bronchiectasis caused by other underlying diseases. (Bronchiectasis occurs when infections or other conditions damage the walls of the airways, causing them “to widen and become loose and scarred” and less able to clear mucus.¹)

Supporting combination clinical trials for potential therapies for people with CF is not new. In the past, we have used this approach for trials of potential NTM treatments. In the end, we believe this strategy will help make therapies available to people with CF sooner. 

¹ What Is Bronchiectasis? National Heart, Lung, and Blood Institute. Updated Oct. 27, 2023. Accessed May 24, 2024. https://www.nhlbi.nih.gov/health/bronchiectasis

• Infections
• Championing a Sustainable Pipeline for Antibiotics
• Research Into Complications