289. Imipenem and Ciprofloxacin Pharmacokinetics (PK) in Critically-Ill Burn Patients Treated with Continuous Venovenous Hemofiltration (CVVH)
Session: Poster Abstract Session: Antimicrobial Therapy: Clinical Studies
Friday, October 21, 2011
Room: Poster Hall B1
Handouts
  • PK-PD IDSA 2011.pdf (555.4 kB)
  • Background: Antimicrobial PK data in burn patients treated with CVVH are scant. .  If clinicians caring for burn patients infected with multidrug resistant pathogens are to improve outcomes, antimicrobial pharmacodynamics (PD) must be optimized using population-specific PK data.  As such, we sought to evaluate PK of commonly-used antimicrobials in critically-ill burn patients receiving CVVH.

    Methods: Adult patients admitted to the US Army Burn ICU who received ciprofloxacin (n=1) or imipenem (n=2) for ≥48 hours and CVVH for ≥24 hours were prospectively enrolled.  Serial pre-filter plasma, post-filter plasma and ultrafiltrate samples were collected pre-dose and at 4 time points during a dosing interval.  Concentrations were measured using a validated high-performance liquid chromatography method.  Plasma concentration-time data was fitted to one- and two- compartment models for PK analysis.

    Results: 

    Patient characteristics, CVVH parameters and PK results are listed in the table.  Given an MIC90 of 1 mg/L for gram negative isolates at our institution, patient 1 achieved a suboptimal PK-PD target (free AUC24:MIC of 24.5), while imipenem-recipients had an appropriate time above MIC of 84.7%.

     

    Patient #1

    Patient #2

    Patient #3

    Patient Characteristics

     

     

     

     

    Weight (kg)

    88

    99

    62

     

    Burn Surface Area (%)

    56.3

    59.1

    4.0

     

    Urine Output (mL/day)

    137

    429

    4346

    CVVH Parameters

     

     

     

     

    CVVH Machine

    PRISMAFLEX®

    NxStage System One®

    PRISMAFLEX®

     

    Filter Type

    HF 1400

    Polyarylethysulfone

    CAR 500

    Polyethersulfone

    HF 1400

    Polyarylethysulfone

     

    Effluent rate (mL/kg/h)

    35.0

    35.0

    33.2

    PK Analysis

     

     

     

     

    Drug

    Ciprofloxacin

    Imipenem

    Imipenem

     

    Regimen

    400 mg IV q8h

    500 mg IV q6h

    500 mg IV q6h

     

    Free Cmax (mg/L)

    2.1

    16.5

    30.2

     

    Free Cmin (mg/L)

    0.5

    0.6

    0.8

     

    Free AUC24 (mg*L/h)

    24.5

    103.8

    326.8

     

    Half-life (h)

    4.0

    1.2

    1.0

     

    Sieving Coefficient

    0.91

    1.01

    0.96

     

    CVVH Clearance (L/h)

    6.2

    3.7

    3.1

     

    % CVVH Clearance

    17.9

    24.3

    68.1

    Conclusion: These preliminary PK results suggest that standard doses of ciprofloxacin may be inadequate in burn patients receiving CVVH, while current dosing of imipenem may be appropriate.


    Subject Category: A. Antimicrobial agents and Resistance

    Jason M. Cota, Pharm.D.1,2, Clinton K. Murray, MD3, Kevin K. Chung, MD4, Elsa C. Coates, RN4 and Kevin S. Akers, MD1, (1)San Antonio Military Medical Center, Fort Sam Houston, TX, (2)University of the Incarnate Word, San Antonio, TX, (3)Brooke Army Medical Center, Ft. Sam Houston, TX, (4)US Army Institute of Surgical Research, Fort Sam Houston, TX

    Disclosures:

    J. M. Cota, None

    C. K. Murray, None

    K. K. Chung, None

    E. C. Coates, None

    K. S. Akers, None

    Findings in the abstracts are embargoed until 12:01 a.m. EST Thursday, Oct. 20 with the exception of research findings presented at IDSA press conferences.