1967. Ceftolozane/Tazobactam Clearance During In Vitro Continuous Renal Replacement Therapy (CRRT)
Session: Poster Abstract Session: Antimicrobial Pharmacokinetics and Pharmacodynamics
Saturday, October 29, 2016
Room: Poster Hall
Posters
  • In vitro ceftolozaneBAMfinal2016.pdf (308.7 kB)
  • Background: To determine ceftolozane/tazobactam (C/T) transmembrane clearances (CLTM) 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 CLTM of C/T were shown in the Table. CVVH & CVVHD CLTM 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)

    Weerachai Chaijamorn, BSc (Pharmacy), BCP, BCPS1, Alexander Shaw, Pharm D2, Susan J. Lewis, PharmD3 and Bruce Mueller, PharmD2, (1)College of Pharmacy, University of Michigan/Faculty of Pharmacy, Siam University, Ann Arbor, MI, (2)College of Pharmacy, University of Michigan, Ann Arbor, MI, (3)College of Pharmacy, University of Findlay, Findlay, OH

    Disclosures:

    W. Chaijamorn, None

    A. Shaw, None

    S. J. Lewis, None

    B. Mueller, None

    Findings in the abstracts are embargoed until 12:01 a.m. CDT, Wednesday Oct. 26th with the exception of research findings presented at the IDWeek press conferences.