IV Colistin for Pulmonary Exacerbations: Improving Safety and Efficacy

Inclusion Criteria: 1. Male or female ≥ 18 years of age at Visit 1. 2. Documentation of CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype and one or more of the following criteria: * Sweat chloride equal or greater than 60 mEq/L by quantitative pilocarpine iontophoresis test. * Two well-characterized mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene * Abnormal nasal potential difference (NPD) as measured by a change in NPD in response to a low chloride solution and isoproterenol of less than -5 mV. 3. Documentation of the presence of an acute pulmonary exacerbation, based on CF Foundation guidelines, as diagnosed by a faculty member of the Denver Adult CF Program. 4. Respiratory culture(s) demonstrating evidence of Pseudomonas aeruginosa or Achromobacter species airway infection. 5. Subject is able to produce sputum, undergo phlebotomy, and provide written consent. 6. The subject's treating physician has determined that they should receive either tobramycin or colistin intravenously as one of the designated agents for their APE treatment. Subjects who are able to receive either tobramycin or colistin as part of their antibiotic regimen will be randomized into one of three arms. If a treating physician deems that a subject cannot receive tobramycin due to vestibular toxicity, ototoxicity or bacterial resistance, the subject will be randomized to either standard or PK-adjusted colistin. Exclusion Criteria: 1. Concomitant administration of bactrim (due to effects on creatinine). 2. Concomitant administration of inhaled colistin for patients in the colistin PK arm, as this will create inaccuracies in colistin sputum concentration measurements. 3. Patients being treated for B. cepacia, due to colistin resistance by the pathogen. 4. Presence of chronic renal insufficiency, with abnormal baseline creatinine \>1.2mg/dL. 5. Presence of a condition or abnormality that in the opinion of the investigator would compromise the safety of the patient or the quality of the data. 6. Inability to perform reproducible spirometry. 7. Inability to expectorate sputum. -