Cefiderocol Pharmacokinetics in Adult Patients With Cystic Fibrosis

Participants will receive 4-6 doses of cefiderocol 2 grams every 6-8 hours, in addition to standard intravenous antibiotic therapy selected by the site. Just prior and then after the final dose, a total of nine blood samples will be collected to measure cefiderocol 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 75% of the dosing interval. These data will be utilized to determine an optimized dosing regimen for adults with CF.

Inclusion criteria

• Documented diagnosis of CF
• Acute pulmonary exacerbation as the primary reason for admission to the hospital with requirement to receive systemic antibiotic treatment

Exclusion criteria

• Females that are pregnant and/or breastfeeding
• 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)
• History of a lung transplant at any time in the past or any other organ transplantation (e.g., liver) within the last 6 months
• Moderate to severe renal dysfunction defined as a creatinine clearance < 60 mL/min (as calculated by the Cockcroft-Gault equation using actual body weight) or requirement for continuous renal replacement therapy or hemodialysis
• A hemoglobin less than 8 gm/dL at baseline
• Any rapidly-progressing disease or immediately life-threatening illness (defined as imminent death within 48 hours in the opinion of the investigator)