Imipenem/Cilastatin/Relebactam Pharmacokinetics, Safety, and Outcomes in Adults and Adolescents With Cystic Fibrosis

Participants will receive 10-14 days of imipenem/cilastatin/relebactam every 6 hours with dose determined per renal function, with or without adjunctive aminoglycoside or fluoroquinolone therapy as determined by local study site. After receiving at least 3 doses (i.e. steady-state), a total of eight blood samples will be collected over one dosing interval to measure imipenem and relebactam 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 both (1) free imipenem concentrations above the minimum inhibitory concentration (MIC) for at least 40% of the dosing interval and (2) free relebactam area under the concentration-time curve at least eight times greater than the MIC. These data will be utilized to determine an optimized dosing regimen for adults and adolescents with CF. Additionally, two weeks after treatment, as part of the exploratory clinical endpoint, patients will complete follow-up pulmonary function tests to determine relative percent increase in FEV1 and return to baseline FEV1 after treatment. These outcomes will be reported descriptively.