Pharmacokinetics of cefiderocol during prolonged intermittent kidney replacement therapy in two patients with septic...

Cefiderocol is a new siderophore cephalosporin for treating severe bacterial infections by Gram-negative pathogens in adults. Significant elimination of the drug will probably occur as a result of kidney replacement therapy, but there are currently insufficient pharmacokinetic data to guide dosing during prolonged intermittent kidney replacement therapy (PIKRT) or the use of the pathogen adsorber Seraph 100.

Pharmacokinetic data were obtained from two critically ill patients undergoing PIKRT and hemoperfusion with the pathogen adsorber Seraph 100. Cefiderocol levels in plasma and dialysate samples were quantified using liquid chromatography with tandem mass spectrometry to evaluate the impact of extracorporeal therapy modalities on cefiderocol pharmacokinetics.

The median cefiderocol dialyser clearance was 80.94 (38.7-87) mL/min, while the Seraph 100 showed no significant clearance [-1.8 (-7.9 to 3.6) mL/min]. The cefiderocol concentration in the total spent dialysate suggests a total elimination of 1350 and 400 mg of cefiderocol, or 68% and 40% of the administered dose.

Cefiderocol is substantially eliminated by PIKRT, but not during hemoperfusion with the Seraph 100. Consequently, dosage adjustments may be necessary depending on the intensity of the PIKRT procedure. Doses used for patients with normal renal function may be required to prevent underdosing during intensive PIKRT.