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Clinical Therapeutics

Pharmacodynamic Target Attainment for Various Ceftazidime Dosing Schemes in High-Flux Hemodialysis

Angela S. Loo, Michael Neely, Evan J. Anderson, Cybele Ghossein, Milena M. McLaughlin, Marc H. Scheetz
Angela S. Loo
New York-Presbyterian/Weill Cornell Medical Center, New York, New York, USAa
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Michael Neely
USC Keck School of Medicine, Los Angeles, California, USAb
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Evan J. Anderson
Emory University School of Medicine, Atlanta, Georgia, USAc
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Cybele Ghossein
Northwestern Memorial Hospital, Chicago, Illinois, USAd
Northwestern University Feinberg School of Medicine, Chicago, Illinois, USAe
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Milena M. McLaughlin
Northwestern Memorial Hospital, Chicago, Illinois, USAd
Midwestern University, Chicago College of Pharmacy, Downers Grove, Illinois, USAf
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Marc H. Scheetz
Northwestern Memorial Hospital, Chicago, Illinois, USAd
Midwestern University, Chicago College of Pharmacy, Downers Grove, Illinois, USAf
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DOI: 10.1128/AAC.00474-13
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Figures

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  • Fig 1
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    Fig 1

    Concentration-time profiles for 6 patients after receiving a 2-g ceftazidime dose (27).

  • Fig 2
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    Fig 2

    Two-compartment models of observed versus predicted serum concentrations of ceftazidime (R2 = 0.803 and 0.988). Predictions are based on the median population parameter values (left) and median individual Bayesian posterior parameter values (right).

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    Fig 3

    Probability of target attainment for 48-h dialysis.

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    Fig 4

    Probability of target attainment for 72-h dialysis.

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    Fig 5

    Simulated concentration-time curves for free ceftazidime for hemodialysis every 72 h (5th, 50th, and 95th percentiles are shown).

Tables

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  • Table 1

    Bayesian posterior density resultsa

    Support pointkel (1/h)V (liters)kCP (1/h)kPC (1/h)Weighting fraction
    10.0609.230.7180.6790.167
    20.0975.822.1831.8550.167
    30.05711.430.8301.6050.167
    40.05110.291.0991.1520.167
    50.0499.920.6441.0720.167
    60.02812.540.2960.6010.167
    • ↵a kel, elimination rate constant; V, volume of distribution; kCP, rate transfer constant from central to peripheral compartment; kPC, rate transfer constant from peripheral to central compartment.

  • Table 2

    Covariance matrix in the lower triangular forma

    ParameterCovariance
    kelVkCPkPC
    kel0.00043
    V−0.040944.420889
    kCP0.011582−1.121610.355167
    kPC0.007308−0.552110.2177210.205454
    • ↵a The full covariances were used in all simulations. See Table 1 and the text for parameter definitions.

  • Table 3

    PTA values for different dosing regimensa

    Dose and frequencyMIC (mg/liter)Probability of target attainment (%)
    45%TMIC, 72-h dialysis period70%TMIC, 72-h dialysis period45%TMIC, 48-h dialysis period70%TMIC, 48-h dialysis period
    Model 1Model 2Model 3Model 1Model 2Model 3Model 1Model 2Model 3Model 1Model 2Model 3
    500 mg q dialysis0.25100100100100100100100100100100100100
    0.5100100100100100100100100100100100100
    1100100100100100100100100100100100100
    2100100100100100100100100100100100100
    4100100100737369100100100100100100
    872705413137100100100767643
    1623001019203550
    32000000000000
    1,000 mg q dialysis0.25100100100100100100100100100100100100
    0.5100100100100100100100100100100100100
    1100100100100100100100100100100100100
    2100100100100100100100100100100100100
    4100100100100100100100100100100100100
    8100100100737369100100100100100100
    1672705413137100100100767643
    3223001019203550
    2000 mg q dialysis0.25100100100100100100100100100100100100
    0.5100100100100100100100100100100100100
    1100100100100100100100100100100100100
    2100100100100100100100100100100100100
    4100100100100100100100100100100100100
    8100100100100100100100100100100100100
    16100100100737369100100100100100100
    3272705413137100100100767643
    500 mg q24h0.25100100100100100100100100100100100100
    0.5100100100100100100100100100100100100
    1100100100100100100100100100100100100
    2100100100100100100100100100100100100
    4100100100100100100100100100100100100
    8100100100100100100100100100100100100
    161001001001009988100100100999844
    3224254119015161650
    1,000 mg q24h0.25100100100100100100100100100100100100
    0.5100100100100100100100100100100100100
    1100100100100100100100100100100100100
    2100100100100100100100100100100100100
    4100100100100100100100100100100100100
    8100100100100100100100100100100100100
    16100100100100100100100100100100100100
    3210010010010099881001001001009843
    • ↵a Model 1, primary model; model 2, primary model with covariance matrix × 3; model 3, full HFHD clearance. q dialysis, every dialysis session; q24h, every 24 h.

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Pharmacodynamic Target Attainment for Various Ceftazidime Dosing Schemes in High-Flux Hemodialysis
Angela S. Loo, Michael Neely, Evan J. Anderson, Cybele Ghossein, Milena M. McLaughlin, Marc H. Scheetz
Antimicrobial Agents and Chemotherapy Nov 2013, 57 (12) 5854-5859; DOI: 10.1128/AAC.00474-13

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Pharmacodynamic Target Attainment for Various Ceftazidime Dosing Schemes in High-Flux Hemodialysis
Angela S. Loo, Michael Neely, Evan J. Anderson, Cybele Ghossein, Milena M. McLaughlin, Marc H. Scheetz
Antimicrobial Agents and Chemotherapy Nov 2013, 57 (12) 5854-5859; DOI: 10.1128/AAC.00474-13
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