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 top priority for the CF Foundation. Building on the success of the initiative, we continue to provide significant financial support for this important issue — more than any other CF complication — including investments 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 modulators have on people with CF, including inflammation, gastrointestinal symptoms and function, liver function, body composition/growth, and CF-related diabetes. 

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. In addition, the participating study sites with expertise in NTM have formed the NTM Consortium, which will be able to accelerate future NTM clinical studies.

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 emergency Investigational New Drug process, 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.
• A large 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.
• Inhaled nitric oxide is being tested in clinical trials as a treatment for Pseudomonas and NTM. Nitric oxide is a molecule produced by our bodies that kills bacteria, breaks up biofilms, and improves the movement of cilia — hair-like structures that help move mucus out of the lungs.
• 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. 

Other potential treatments that are being tested include:

• New formulations and new uses of existing antibiotics
• A drug that would protect the inner ear and prevent hearing loss caused by aminoglycosides — commonly used antibiotics, such as tobramycin and amikacin
• A drug that would prevent Aspergillus fungal infections in lung transplant recipients  
• A drug that could eventually be used to treat NTM infections

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

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 upcoming 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. 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 (mucus or phlegm coughed up from the lungs) while taking CFTR modulators. 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. 

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 include people with CF and other people who suffer chronic infections such as individuals with non-CF bronchiectasis. (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 and an antifungal treatment for lung transplant recipients. 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

During Plenary 2 of the 2023 North American Cystic Fibrosis Conference, Lucas Hoffman, MD, PhD, and Natalie West, MD, MHS, discussed the current landscape of CF infections, including the latest clinical research. Dr. Hoffman provided an overview of infections in cystic fibrosis, how they are changing in the context of modulators, and what challenges are emerging. Dr. West focused on the development of new treatments in CF and described novel approaches to managing CF infections with the goal of improving the lives of all people with CF.

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