Cystic Fibrosis (CF) is an inherited, life-limiting disease affecting over 11,300 people in the UK and approximately 188,000 people globally.
People with CF experience a build-up of thick sticky mucus in the lungs, digestive system and other organs. This causes a wide range of challenging symptoms affecting the entire body. In the lungs, thick sticky mucus traps bacteria, making cystic fibrosis infections difficult to clear.
New treatments like CFTR modulator therapies have improved outcomes for many people with CF. However, not everyone with CF can benefit from these treatments. The impact of CFTR modulator therapies on lung infections is not yet fully understood. Several critical gaps remain, underscoring the continued need for new antimicrobials and diagnostics.
Antibiotics are routinely used to manage infections which can be persistent. Over time and due to resistance, recurrent infections become difficult to treat, leading to irreversible lung damage. Antimicrobials are vital to managing acute infections, known as exacerbations, and long-term chronic infections.
The discovery and development of new antimicrobials and diagnostics to manage pulmonary infections in CF remains an urgent unmet need.
Antimicrobial Resistance
Antimicrobial Resistance: Persistent infections, such as those caused by Pseudomonas aeruginosa and nontuberculous mycobacteria (NTM), continue to threaten lung function and quality of life and long term survival for people with CF. These infections are often resistant to multiple antibiotics and require prolonged, complex treatment regimens, including inhaled, oral, and intravenous therapies.
The cumulative burden of care associated with managing chronic infection is substantial. People with CF report significant treatment fatigue, time commitment, and disruption to daily life, particularly where therapies are poorly tolerated or only partially effective. New therapeutic approaches are needed to address these CF treatment challenges and to reduce treatment duration while improving tolerability and effectiveness against resistant pathogens.
Diagnostic Limitations: Current diagnostic tools often fail to detect infections early or accurately, delaying treatment and leading to chronic infection or disease progression. Sputum remains the primary sample type used for diagnosis, but its availability is increasingly limited, particularly for people receiving CFTR modulator therapies who may produce little or no sputum.
People with CF and clinicians report that changes in symptoms and exacerbation patterns associated with CFTR modulator use can make infection harder to recognise, further complicating clinical decision making. Many people on modulators report changes in exacerbation symptoms, which can delay clinical management and allow infections to persist.
There is a strong unmet need for improved diagnostics that are sensitive, rapid, and suitable for routine monitoring, including tools that can detect infection earlier, guide targeted therapy, and reduce reliance on burdensome sampling methods.
Common Pathogens in Cystic Fibrosis
The common key problematic pathogens in CF are
- Pseudomonas aeruginosa (chronic and intermittent),
- Burkholderia cepacia complex, non-tuberculosis mycobacteria such as Mycobacterium abscessus,
- Haemophilus influenzae, methicillin-resistant Staphylococcus aureus, as well as Aspergillus species.
Why CF differs from other AMR diseases?
CF presents unique challenges for antimicrobial development:
- Biofilm Formation – CF bacteria form biofilms in the lung. Together with the thick mucus accumulating in the lung, this makes antimicrobial penetration very difficult.
- Two Disease States – Two disease states exist, chronic and acute (with periodic flare-ups or exacerbations). Both require different treatment strategies.
- Lab-to-Clinic Disconnect – The adaptation of microbes to the unique host environment creates a disconnect between antimicrobial susceptibility testing (data produced in the lab) and clinical outcomes (what is seen in patients). This necessitates the use of clinical strains for antimicrobial development.
CF as a Model for Chronic Respiratory Infection Research
The CF research landscape offers a uniquely focused and coordinated community, providing innovators with the environment and expertise needed to accelerate discovery and development. CF’s well-defined patient population, combined with established academic and clinical networks, makes it an ideal testbed for advancing new antimicrobial and diagnostic solutions.
Through the CF AMR Syndicate, innovators can access expertise spanning the entire discovery-to-clinic pathway. Established CF academic and clinical trial networks provide innovators with support to design and deliver robust studies.
Contact CF AMR Syndicate
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