Population Pharmacokinetics and Safety of Intravenous Ceftolozane/Tazobactam in Adult Cystic Fibrosis Patients

Participants will receive 4-6 doses of ceftolozane/tazobactam 3 grams every 8 hours, in
addition to standard intravenous antibiotic therapy selected by the site. Just prior and then
after the final dose, a total of six blood samples will be collected to measure ceftolozane
and tazobactam concentrations. Data will be fit to a population pharmacokinetic model. The
final model will be utilized in a Monte Carlo simulation to determine the probability of
several different dosing regimens retaining concentrations above the minimum inhibitory
concentration (MIC) for at least 39% of the dosing interval. These data will be utilized to
determine an optimized dosing regimen for adults with CF.

Inclusion Criteria:

1. Age 18 years or older

2. Documented diagnosis of CF

3. Acute pulmonary exacerbation as the primary reason for admission to the hospital with
requirement to receive systemic antibiotic treatment

4. If female, subjects must be non-pregnant and non-lactating. Females can be either not
of a child-bearing potential or if of a child-bearing potential, on acceptable modes
of birth control such as abstinence from sexual intercourse, oral/parenteral
contraceptives, or barrier method

Exclusion Criteria:

1. History of any moderate or severe hypersensitivity or allergic reaction to any
β-lactam antibiotic (a history of mild rash to a cephalosporin followed by uneventful
re-exposure is not a contraindication)

2. Prior (within 24 hours of first dose of study drug) or concomitant receipt of
piperacillin/tazobactam or probenecid

3. History of lung transplant

4. Moderate to severe renal dysfunction defined as a creatinine clearance < 50 mL/min (as
calculated by the Cockcroft-Gault equation using actual body weight) or requirement
for continuous renal replacement therapy or hemodialysis

5. A hemoglobin less than 8 gm/dl at baseline

6. Any rapidly-progressing disease or immediately life-threatening illness (defined as
imminent death within 48 hours in the opinion of the investigator)

7. Any condition or circumstance that, in the opinion of the investigator, would
compromise the safety of the patient or the quality of study data

8. Planned or prior participation in any other interventional drug study within 30 days