The purpose of this study is to determine whether choosing antibiotics based on a biofilm antimicrobial susceptibility assay rather than a conventional planktonic antimicrobial susceptibility assay to treat CF patients with chronic P. aeruginosa infection with an acute pulmonary exacerbation is a safe intervention that will result in improved microbiological and clinical outcomes and decrease markers of pulmonary inflammation.

Cystic fibrosis (CF) is the most common fatal genetic condition in the Caucasian population and affects over 3,000 Canadians. Respiratory failure caused by chronic pulmonary infection is the primary cause of death in CF patients. The improved life expectancy of CF patients in the past several decades is due in part to the more aggressive use of antibiotics in the treatment of respiratory infections. However, there is currently no antimicrobial susceptibility assay that can predict which antibiotics will result in improved patient outcomes. Since Pseudomonas aeruginosa is known to grow as a resistant biofilm in the CF lung, antimicrobial susceptibility testing based on biofilm growth of P. aeruginosa may lead to different antibiotic choices that significantly decrease the pulmonary bacterial density of P. aeruginosa. A biofilm antimicrobial susceptibility assay thus has the ability to change the way antibiotics are chosen to treat CF patients and result in improved lung function and longer lives for all CF patients.

Inclusion Criteria:

• Diagnosis of CF based on the following: sweat chloride > 60 mEq/L or genotype with 2 identifiable mutations consistent with CF; and one or more clinical features consistent with CF
• Chronically infected with P. aeruginosa (>50% of respiratory specimens positive for P. aeruginosa in the 24 months prior to screening)
• Able to produce sputum (expectorated or induced)
• Able to reproducibility perform pulmonary function testing
• Written informed consent provided

Exclusion Criteria:

• Sputum culture negative for P. aeruginosa or with a density of less that 10^5 CFU/g at screening
• Sputum culture positive for Burkholderia cepacia at screening
• History of B. cepacia positive respiratory culture within 24 months prior to screening
• Use of antibiotics other than those prescribed by the principal investigator
• History of allergy (urticarial rash, diffuse erythroderma, serum sickness) to more than two groups of antibiotics (aminoglycosides, penicillins, cephalosporins, monobactams, macrolides, or quinolones) that are a therapeutic option
• History of anaphylaxis or other life threatening complication to any antibiotic in the six groups that are a therapeutic option
• Post lung transplantation or listed for lung transplantation
• Pregnancy
• A septic or clinically unstable patient
• Presence of a condition or abnormality that in the opinion of an investigator would compromise the safety of the patient or the quality of the data