Research Into Infections

Why Are Infections a Problem in CF?

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 susceptible to infections from bacteria, viruses, and fungi because abnormally thick, sticky mucus traps these germs in the airways. They also are prone to infections because their mucus and airway liquid 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.

Infections take a significant physical and mental toll on people with cystic fibrosis and remain a top concern. To make meaningful progress against this complex challenge, we have established the Infection Research Initiative to help improve the detection, diagnosis, prevention, and treatment of infections.

What Basic Research Is Being Conducted?

Long-term lung infections are a serious, ongoing threat to the lives of people with CF; therefore, the Foundation funds more research programs focused on infections than any other CF complication.

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 that other microorganisms can cause to the lungs. Studying these interactions helps researchers develop better strategies to manage and treat infections.

Jennifer Bomberger, PhD, an associate professor of medicine at the University of Pittsburgh, answers questions from the CF community, such as whether a less serious bacteria can prevent the dominance of a more dangerous bacteria.

A new area of research will explore how microorganisms, such as bacteria, respond to the changing environment in the lungs once people start taking cystic fibrosis transmembrane conductance regulator (CFTR) modulators and eventually other drugs that target the underlying defect of CF.

Difficult-to-treat infections are another area of focus for researchers. Because more people with CF are getting nontuberculous mycobacteria (NTM) infections, we have funded ongoing research to learn more about them. Work done by the Foundation-funded Colorado CF Research Development Program helps with clinical care and lays the groundwork for developing new treatments for NTM infections. 

The Therapeutics Development Network is conducting studies to create standard ways to diagnose and treat NTM. The participating study sites with expertise in NTM have formed the NTM Consortium, which will be able to accelerate future NTM clinical studies.

The CF Foundation also has funded several programs to identify promising molecules that could be used to treat NTM by capitalizing on advances made by the Bill and Melinda Gates Foundation during its efforts to improve treatment for tuberculosis. (NTM is a bacterial cousin of the bacteria that causes tuberculosis.)

What Treatments Are Being Developed?

The Foundation is funding the development of a wide range of treatments to address infections. In addition, researchers are exploring when to treat, how long to treat, and what medications to use. 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 is under development and aims to continue to study the use of oral antibiotics for outpatient pulmonary exacerbations in children with CF. The STOP 360 trial will compare the use of one IV antibiotic versus two IV antibiotics to treat certain infections in adults. 

To address drug-resistant bacteria, the Foundation is supporting clinical research into unique treatments — such as gallium, nitric oxide, and bacteriophage therapy — that work differently than typical antibiotics.

To grow, bacteria rely on some processes that require iron. If gallium — an atom nearly identical to iron — is used instead, it can disrupt these processes. For example, gallium has been shown to kill antibiotic-resistant strains of Pseudomonas in laboratory research. Intravenous (IV) gallium and an inhaled version are being tested in clinical trials in people with CF.

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.

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 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.

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

The Foundation also is supporting research into fungal infections, especially those caused by Aspergillus fumigatus. This type of fungus can cause complications when it becomes invasive or when it causes an allergic reaction called allergic bronchopulmonary aspergillosis (ABPA). A large-scale study into Aspergillus infections is being planned.

To learn more about key infection research priorities including NTM, Aspergillus, and phage therapy, you can read the Infection Research Handout or watch the webinar, “Research Overview: Infections.” The webinar, hosted on Aug. 25, 2020, brought together research experts and members of the Infection Research Initiative Steering Committee to discuss the latest updates in infection research.

What Are the Current Treatments?

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

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