The purpose of this study is to find the safest and most effective way to administer IV antibiotics to treat acute pulmonary exacerbations (APEs) in patients with cystic fibrosis (CF) that are caused by pathogens, like Pseudomonas aeruginosa. This study will test the safety and effectiveness of two commonly prescribed IV antibiotics: tobramycin and colistin. Though regularly used, not much is known about how these drugs compare with each other in terms of their toxicities, both during short term treatment of an APE and after many treatment courses with these drugs over many years. There are currently no guidelines on the safest and most effective antibiotics to use when treating APEs. We will study kidney function, sputum cultures, and treatment outcomes in patients receiving routine administration of one of these two IV antibiotics. We will also test these outcomes in patients receiving a less frequent dosing schedule for IV colistin. The hope is that this new schedule for IV colistin, which is twice a day and adjusted based on blood and urine tests, will reduce harmful side effects, such as kidney damage, while still being a powerful treatment against CF microbial pathogens.

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. -

14 days

The total number of participants at risk in each arm of the study represents the number enrolled in each arm of the study, not the total number enrolled. The study arms were not enrolled equally.