Cystic fibrosis is a heterogeneous, autosomal recessive genetic disease associated with abnormal exocrine gland function, which affects multiple organs, including the gastrointestinal, pulmonary, and reproductive systems. Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane regulator gene, which is associated with abnormal ion transport in epithelial cells. Due to early recognition and advances in treatment, the median survival in patients has increased from under 2 years to over 30 years of age.
Lung disease is the major cause of morbidity and mortality in cystic fibrosis, accounting for the majority of deaths . At least 50% of patients are hospitalized at least once a year for treatment of a pulmonary exacerbation. Recurrent infections are associated with a progressive decline in lung function leading to respiratory failure.
Patients with cystic fibrosis experience a chronic progressive loss of lung function associated with infection, inflammation, and tissue destruction. The most common bacteria implicated in lung infections associated with cystic fibrosis are Haemophilus influenzae, Staphylcoccus aureus, and Pseudomonas aeruginosa . Pseudomonas aeruginosa is found in the lower respiratory tract of nearly 70% of cystic fibrosis patients by age 17 years , and over 90% of patients have at least one culture positive for P. aeruginosa during their lifetime. Chronic pulmonary infection caused by P. aeruginosa contributes to a progressive decline in lung function and the development of obstructive lung disease. Additionally, lung function declines more rapidly once colonization with P. aeruginosa has occurred. When colonization with P. aeruginosa is present, the organism is commonly a mucoid phenotype that is more resistant to antibiotic penetration. Thus, antimicrobial therapy directed against this organism plays a central role in the management of acute exacerbation and potentially on a chronic basis.
Currently, the primary role of aerosolized antibiotics is for patients with cystic fibrosis. Patients with cystic fibrosis experience frequent and recurrent lung infections as a result of their disease. Aminoglycosides, including tobramycin, exhibit good activity against gram-negative bacteria that are frequently implicated in these infections, including P. aeruginosa.
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