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Date of Award

Spring 2023

Degree Name

Master of Medical Science (Physician Assistant)

Department

Physician Assistant; College of Health Sciences

First Advisor

Diana Hawthorne

Abstract

Mutations in both copies of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, located on chromosome 7, result in defective, absent, or insufficient quantities of the CFTR protein. This leads to mucus hyperviscocity and impaired mucociliary clearance. Additional abnormal processes lead to a cycle of inflammation, bronchial obstruction, and infection which ultimately leads to lung injury. This allows opportunistic pathogens, such as Pseudomonas aeruginosa, to cause infection in the lungs of cystic fibrosis patients. Treatment of Pseudomonas aeruginosa in the lungs of cystic fibrosis patients should be based on susceptibility reports, efficacy, adjunct properties, patient burden of treatment, and treatment adverse effects. P. aeruginosa has the highest resistance rate against cephems (48%) and the lowest against colistin (5%). Combination therapy of aztreonam lysine inhalation solution and tobramycin inhalation solution demonstrates the greatest efficacy based on change in P. aeruginosa sputum density, change in FEV1%, and exacerbation frequency. Furthermore, colistin was shown to be more effective in biofilm/mucus mixtures compared to tobramycin. Adjunct treatment options include azithromycin, novel monoclonal antibodies, and bacteriophages which provide anti-inflammatory properties. Effective treatment of P. aeruginosa increases the lifespan and quality of life of cystic fibrosis patients.

Additional Files

Capstone Poster.pdf (16229 kB)

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Therapeutic Approach to Pseudomonas aeruginosa Infection in Cystic Fibrosis Patients

Mutations in both copies of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, located on chromosome 7, result in defective, absent, or insufficient quantities of the CFTR protein. This leads to mucus hyperviscocity and impaired mucociliary clearance. Additional abnormal processes lead to a cycle of inflammation, bronchial obstruction, and infection which ultimately leads to lung injury. This allows opportunistic pathogens, such as Pseudomonas aeruginosa, to cause infection in the lungs of cystic fibrosis patients. Treatment of Pseudomonas aeruginosa in the lungs of cystic fibrosis patients should be based on susceptibility reports, efficacy, adjunct properties, patient burden of treatment, and treatment adverse effects. P. aeruginosa has the highest resistance rate against cephems (48%) and the lowest against colistin (5%). Combination therapy of aztreonam lysine inhalation solution and tobramycin inhalation solution demonstrates the greatest efficacy based on change in P. aeruginosa sputum density, change in FEV1%, and exacerbation frequency. Furthermore, colistin was shown to be more effective in biofilm/mucus mixtures compared to tobramycin. Adjunct treatment options include azithromycin, novel monoclonal antibodies, and bacteriophages which provide anti-inflammatory properties. Effective treatment of P. aeruginosa increases the lifespan and quality of life of cystic fibrosis patients.