730. Colistin Pharmacokinetics and Pharmacodynamics in Burn Patients During Continuous Venovenous Hemofiltration
Session: Poster Abstract Session: Antimicrobials: PK/PD Studies
Friday, October 4, 2013
Room: The Moscone Center: Poster Hall C
Posters
  • Colistin CVVH PK-PD IDSA 2013.pdf (227.0 kB)
  • Background:   There are few reports describing the pharmacokinetic (PK) behavior of colistin during continuous venovenous hemofiltration (CVVH), often used in critical care settings for acute kidney injury.  We determined colistin PK parameters in two burn patients, including one with and without CVVH.

    Methods:   Plasma and ultrafiltrate samples were obtained from 2 burn patients undergoing treatment with colistin methanesulfonate (CMS) before, and at 1, 2, 4, 8 and 12 hours after the start of 30-min infusions.  Patient 1 was sampled during CVVH, while Patient 2 was sampled before (2A) and during (2B) CVVH therapy.  Free and total colistin concentrations were measured as the sum of colistin E1 and E2 by high-performance liquid chromatography using a validated assay.  PK parameters were estimated by non-compartmental analysis (WinNonLin, Pharsight, Inc.).  The sieving coefficient, representing the fraction of colistin crossing the filter membrane, and clearance attributable to CVVH were calculated. 

    Results:   Determination of PK parameters in Patient 2B were limited by filter clotting at hour 8.  Clinical and PK parameters were:

     

    Patient 1

    Patient 2A

    Patient 2B

    Age/Gender

    68yo M

    37yo M

    37yo M

    % TBSA Burn

    10.6%

    51%

    51%

    CVVH Dose (mL/kg/h)

    23.4

    --

    32.0

    Machine & Filter Type

     

    PrismaFlex®, HF1400 (Polyarylethersulfone)

    --

    NxStage®, CAR500 (Polyethersulfone)

    CMS Dose (mg/kg)

    2.2

    1.5

    2.2

    Cmax (µg/mL)

    13.6

    3.4

    6.7

    AUC12 (h·µg/mL)

    111.1

    27.5

    50.0*

    Vd (L)

    86.1

    99.7

    --

    T-1/2 (h)

    22.0

    11.9

    --

    Sieving Coefficient

    0.44

    --

    0.14*

    Mean % Free Drug

    11.9 ± 9.2%

    13.7 ± 6.4%

    10.9 ± 4.6%

    Total Clearance (L/h)

    2.7

    4.7

    --

    CVVH Clearance (L/h)

    1.4

    --

    0.04

    % CVVH Clearance

    51.6%

    --

    --

                                                                                                * determined using hour 0 to 8 data

    The ratio of the area under the 24-hour time-concentration curve to minimal inhibitory concentration (AUC24:MIC) ≥ 60 was achieved at colistin MICs of 2, 0.75 and 1 µg/mL for Patient 1, 2A and 2B, respectively. 

    Conclusion:   Colistin pharmacokinetics and pharmacodynamics can vary significantly between individuals, as a result of dosing and physiologic circumstances.   Additional data are required to fully characterize the impact of adjunctive life support therapies such as CVVH.

    Kevin S. Akers, MD1,2, Jason M. Cota, PharmD, MSc3, Kevin K. Chung, MD1 and Clinton K. Murray, MD4, (1)US Army Institute of Surgical Research, Fort Sam Houston, TX, (2)Brooke Army Medical Center, Ft. Sam Houston, TX, (3)Univ. of the Incarnate Word, Feik Sch. of Pharmacy, San Antonio, TX, (4)Brooke Army Medical Center, Fort Sam Houston, TX

    Disclosures:

    K. S. Akers, None

    J. M. Cota, None

    K. K. Chung, None

    C. K. Murray, None

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