Ceftolozane/Tazobactam Clearance During In Vitro Continuous Renal Replacement Therapy (CRRT)

Background: To determine ceftolozane/tazobactam (C/T) transmembrane clearances (CL_TM) and membrane adsorption in continuous hemofiltration (CVVH) and continuous hemodialysis (CVVHD).

Methods: A validated in vitro bovine blood CVVH & CVVHD model using polysulfone (HF1400) & AN69 (Multiflow 150-M) hemofilters was performed to evaluate transmembrane clearances at different effluent flow rates. Adsorption experiments of C/T over 1 hour were determined in the study for each filter type. Each experiment was repeated 6 times with a new filter.

Results: The mean C/T sieving coefficient (SC) values from CVVH with three different ultrafiltration flow rates (16, 33, and 50 mL/min) ranged from 1.01-1.05 for ceftolozane and 1.27-1.31 for tazobactam from both hemofilters. For CVVHD with either filter, the mean saturation coefficients (SA) determined from four different dialysis flow rates (16, 33, 50 and 100 mL/min) of ceftolozane ranged from 0.70-1.04. Mean tazobactam SAs ranged from 1.09-1.32. Both SC and SA values were not different at any effluent rates. CVVH and CVVHD CL_TM of C/T were shown in the Table. CVVH & CVVHD CL_TM for both hemodiafilter types were not significantly different from each other. No C/T adsorption occurred for either hemodiafilter.

Conclusion: CRRT clearances of C/T depend on effluent flow rates but not hemofilter type. Adsorption of C/T did not influence CRRT clearance substantially. The C/T CRRT clearance with commonly prescribed CRRT rates (35-50 mL/min) are approximately 90%/25% (respectively) of reported non-renal C/T clearance values in anuric patients. Dosage adjustment is likely necessary for CRRT.

Table C/T CVVH and CVVHD Transmembrane Clearances

Effluent rates	Mean(SD) Ceftolozane CLTM (mL/min)		Mean(SD)Tazobactam CLTM (mL/min)
	HF 1400	AN 69	HF 1400	AN 69
CVVH
16 mL/min	17.46 (1.27)	16.97 (2.51)	21.82 (1.53)	21.10 (3.43)
33 mL/min	33.93 (5.86)	34.55 (2.67)	37.78 (10.94)	42.85 (4.36)
50 mL/min	50.56 (4.39)	51.06 (3.79)	64.13 (7.16)	64.83 (9.13)
CVVHD
16 mL/min	16.31 (3.48)	17.28 (2.52)	19.50 (2.71)	20.01 (1.70)
33 mL/min	33.97 (8.69)	30.14 (9.09)	42.52 (6.64)	36.25 (9.60)
50 mL/min	45.69 (12.28)	51.39 (13.18)	62.96 (12.98)	66.07 (17.04)
100 mL/min	86.06 (12.65)	70.23 (15.34)	124.29 (16.36)	110.33 (21.01)