The primary purpose of the study is to determine the degree of penetration of cefiderocol into infected lung tissue in hospitalized adults with bacterial pneumonia who are being mechanically ventilated.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
7
Administered intravenously, at a dosage determined based on renal function.
Standard of care antibiotic treatment for pneumonia
Anschutz Medical Campus
Aurora, Colorado, United States
Hartford Hospital
Hartford, Connecticut, United States
University of Florida
Jacksonville, Florida, United States
U Miami Health Tower
Miami, Florida, United States
Concentration of Cefiderocol in Epithelial Lining Fluid
Samples for determination of cefiderocol concentrations in the epithelial lining fluid (ELF) were collected by bronchoalveolar lavage (BAL) procedure on the inflamed section of the lung (ie, a lobe where pneumonia was expected to be present based on chest radiologic imaging) after multiple doses of cefiderocol sufficient to approximate steady state concentrations in blood. The ELF sample for the determination of cefiderocol concentrations was collected at 3 hours after the start of administration of cefiderocol for the first 4 enrolled participants and at 2 hours after the end of infusion for the following 3 participants. Cefiderocol concentrations were determined using liquid chromatography/tandem mass spectrometry (LC/MS/MS), with a lower limit of quantification of cefiderocol in ELF of 0.005 μg/mL. Cefiderocol concentrations in ELF were calculated using cefiderocol concentrations in BAL, adjusted by the ratio of urea concentrations in blood and BAL.
Time frame: At the third dosing (or sixth dosing for participants with severe renal impairment; 16 or 40 hours after first dose, respectively), at 3 hours after the start of the infusion or 2 hours after the end of infusion.
Ratio of the Concentration of Cefiderocol in Epithelial Lining Fluid Relative to Plasma
The concentration of cefiderocol in ELF to plasma ratio (RC,E/P) represents the penetration of cefiderocol into infected lung tissue. ELF and plasma cefiderocol concentrations were determined using liquid chromatography/tandem mass spectrometry (LC/MS/MS). The lower limit of quantification of cefiderocol in plasma and ELF was 0.1 μg/mL and 0.005 μg/mL, respectively.
Time frame: At the third dosing (or sixth dosing for participants with severe renal impairment; 16 or 40 hours after start of the first dose, respectively), at 3 hours after the start of the infusion or 2 hours after the end of infusion.
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North Western University
Chicago, Illinois, United States
Creighton University
Omaha, Nebraska, United States
Weill Cornell Medical College
New York, New York, United States