Persistent Bacterial Infections in Cystic Fibrosis Patients: Exploring Lung Pathophysiology and Antibiotic Challenges

Abstract

Introduction: With over 100,000 people affected worldwide, Cystic Fibrosis (CF) is a genetic condition caused by the dysfunction of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein. This defect impacts the cells, tissues, and glands responsible for producing mucus and sweat. Normally, mucus acts as a protective barrier in the airways and the body. In CF, dysfunctional CFTR leads to thick and sticky mucus, clogging airways and impairing organ function. CF was an untreatable disease with high childhood fatality, but scientific advancements have now provided effective treatment options. Persistent bacterial infections significantly impact CF morbidity and mortality, necessitating comprehensive studies to understand these associations. This paper presents a clinician-targeted review investigating bacterial adaptations in CF lungs, their role in treatment-resistant infections, and strategies to mitigate these challenges.

Methods: A review analyzed factors influencing bacterial persistence in CF patients, utilizing sources including PubMed, ScienceDirect, Frontiers, and ATS Journals. Keywords used were CF pathophysiology, bacterial adaptations, treatment resistant, CFTR, antibiotic delivery. Existing research data were compared across different patient groups, antibiotics, and bacteria strains to identify patterns related to antimicrobial resistance, mucus properties, and population age. 

Results: Impaired mucociliary clearance and increased mucus viscosity are expected to contribute to bacterial colonization and treatment resistance. Dysfunctional immune responses facilitate persistent infections by impairing immune clearance mechanisms due to chronic neutrophil-dominated inflammation. Bacterial adaptations, particularly antibiotic resistance mechanisms, enable bacteria to evade treatment, perpetuating infections.  

Discussion: Bacterial persistence in CF patients is exacerbated by thick mucus and advanced bacterial resistance mechanisms such as biofilm formation and efflux pumps. Early initiation of therapies like Trikafta® significantly improves lung function and reduces infection rates, highlighting the importance of addressing both bacterial adaptations and the CF lung environment. Future research should focus on combination therapies and treatments personalized to genetic profiles.

Conclusion: The study emphasizes the critical interplay between CF lung conditions and bacterial resistance, underscoring the need for innovative therapies. Early intervention with treatments like Trikafta® improves outcomes by enhancing mucus clearance and reducing infection rates. Future research should prioritize combination therapies and personalized approaches to manage chronic infections and improve CF patient quality of life.