731. Population Pharmacokinetics and Pharmacodynamics of Imipenem in Burn Patients Receiving Continuous Venovenous Hemofiltration
Session: Poster Abstract Session: Antimicrobials: PK/PD Studies
Friday, October 4, 2013
Room: The Moscone Center: Poster Hall C
Posters
  • IMP CVVH IDSA 2013.pdf (283.9 kB)
  • Background: Critically ill patients may require continuous venovenous hemofiltration (CVVH) for renal support, and therapy with imipenem/cilastatin for infection by resistant bacteria. We used a population pharmacokinetic (PK) approach to estimate imipenem PK parameters during CVVH.

    Methods: Plasma samples were obtained from burn patients undergoing treatment before, and at 1, 2, 4 and 6 hours after the start of 30-min infusions of 500mg imipenem/cilastatin while receiving CVVH. Sampling was truncated in two subjects due to death and filter clotting. Imipenem concentrations were measured by high-performance liquid chromatography (HPLC) using a validated assay. Data were optimally fit to a one-compartment model with first-order elimination, and time above arbitrary MICs (T>MIC) was determined using WinNonLin (Pharsight, Inc.), using 40% of the dose interval as a target. Typical values (tv) for volume of distribution (V), clearance (CL) and a lag-time parameter (Tlag) required for optimal fitting, were estimated by population PK software (NLME, Pharsight, Inc.). Potential covariates were screened for significance, and the model was validated by 250 bootstrap replicates. Parameter estimates were compared to available literature values.

    Results: 20 samples from 5 subjects (2 male/3 female, 56 19 yrs, 42.7 25.5% total body surface area burned, CVVH dose 27.5 7.2 mL/kg/h) were available for inclusion. T>MIC could not be determined for two subjects due to limited sampling. T>MIC ≥ 40% was achieved for MICs of 4 g/mL (2 subjects) and 8 g/mL (1 subject). Significant covariates for V included current body weight, serum creatinine and CVVH clearance of imipenem.

     

    Model

    tvV (L)

    tvCL (L/h)

    tvTlag (h)

    Base

    22.2

    9.1

    0.9

    Covariate (95% CI)

    26.5 (26.4-26.7)

    9.1 (9.19.2)

    0.9 (0.90-0.91)

    Bootstrap median (95% CI)

    26.6 (18.5-57.6)

    9.1 (8.0-14.8)

    0.9 (0.3-1.0)

    Conclusion: Our estimates of V and CL of imipenem in burn patients during CVVH are consistent with published values. Individual achievement of T>MIC ≥ 40% could be compromised for MICs above 4 g/mL.

    Kevin S. Akers, MD1,2, Jason M. Cota, PharmD, MSc3, Kevin K. Chung, MD1 and Clinton K. Murray, MD2, (1)US Army Institute of Surgical Research, Fort Sam Houston, TX, (2)Brooke Army Medical Center, Fort Sam Houston, TX, (3)Univ. of the Incarnate Word, Feik Sch. of Pharmacy, San Antonio, TX

    Disclosures:

    K. S. Akers, None

    J. M. Cota, None

    K. K. Chung, None

    C. K. Murray, None

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