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Pharmacology

Cefepime Pharmacokinetics in Critically Ill Pediatric Patients Receiving Continuous Renal Replacement Therapy

Gideon Stitt, Jennifer Morris, Lindsay Schmees, Joseph Angelo, Ayse Akcan Arikan
Gideon Stitt
aDepartment of Pharmacy Services, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
bDepartment of Pharmacy Services, Texas Children’s Hospital, Houston, Texas, USA
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Jennifer Morris
bDepartment of Pharmacy Services, Texas Children’s Hospital, Houston, Texas, USA
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Lindsay Schmees
bDepartment of Pharmacy Services, Texas Children’s Hospital, Houston, Texas, USA
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Joseph Angelo
cDepartment of Pediatrics, Renal Section, Baylor College of Medicine, Houston, Texas, USA
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Ayse Akcan Arikan
cDepartment of Pediatrics, Renal Section, Baylor College of Medicine, Houston, Texas, USA
dDepartment of Pediatrics, Section of Critical Care Medicine, Baylor College of Medicine, Houston, Texas, USA
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DOI: 10.1128/AAC.02006-18
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Tables

  • TABLE 1

    Patient demographics

    CharacteristicData by patient
    1234
    Age (yr)1.10.60.55
    SexMaleFemaleMaleMale
    Hospital admission diagnosisLiver transplantLiver failureHyponatremiaHLHa
    Estimated dry wt (kg)1065.425
    Body surface area (m2)0.450.330.330.94
    Baseline SCr (mg/dl)b0.14Unknownc0.150.3
    SCr at CRRT initiation (mg/dl)0.410.530.593.37
    Mean urine output at CRRT initiation (ml/kg/h)d1.31.61.40.25
    Mean urine output at sampling (ml/kg/h)e0.220.640.070
    Cefepime dose (mg/kg)f48575564
    Dosing interval (h)88612
    Infusion time (h)30.50.50.5
    No. of samples collected3233
    No. of doses received prior to first sample18372
    • ↵a HLH, hemophagocytic lymphohistiocytosis.

    • ↵b SCr, serum creatinine.

    • ↵c Unknown baseline SCr level due to transfer from outside hospital.

    • ↵d 24 h prior to CRRT initiation.

    • ↵e 48 h around the time of sampling.

    • ↵f Based on estimated dry weight.

  • TABLE 2

    CVVHDF parameters

    ParameterData by patient
    1234
    Dialysate (ml/h)1,5001,000550650
    Pre-filter replacement (ml/h)500450500600
    Post-filter replacement (ml/h)50505050
    Blood flow (ml/min)904070100
    Blood flow (ml/kg/min)96.7134
    Normalized effluent rate (ml/1.73 m2/h)8,7508,5936,0893,076
    Effluent urea/BUN ratioa0.750.750.750.77
    Delivered CVVHDF clearance (ml/1.73 m2/h)b6,5636,4454,5672,369
    Circuit age (h)c22.633.815.211.2
    • ↵a BUN, blood urea nitrogen.

    • ↵b Delivered CVVHDF clearance = normalized effluent rate × BUN/effluent urea nitrogen ratio.

    • ↵c Measured from circuit change to time of cefepime dose prior to sampling.

  • TABLE 3

    Calculated PK and PD parameters

    ParameterData by patient
    1234
    ke (h−1)0.240.440.670.31
    T1/2 (h)a2.91.612.2
    Vd (liters/kg)0.230.170.120.04
    Cl (liters/h/kg)0.0550.0750.080.012
    Calculated free Cmax (μg/ml)b138.6244.8306.41,268.2
    Calculated free Cmin (μg/ml)c22.79.17.738.6
    %fT>1×MICd10010098.3100
    %fT>4×MICd82.363.865100
    • ↵a T1/2, half-life.

    • ↵b Back-extrapolated to the end of the infusion.

    • ↵c Extrapolated to the end of the scheduled dosing interval.

    • ↵d Based on a presumed MIC of 8 μg/ml.

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Cefepime Pharmacokinetics in Critically Ill Pediatric Patients Receiving Continuous Renal Replacement Therapy
Gideon Stitt, Jennifer Morris, Lindsay Schmees, Joseph Angelo, Ayse Akcan Arikan
Antimicrobial Agents and Chemotherapy Mar 2019, 63 (4) e02006-18; DOI: 10.1128/AAC.02006-18

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Cefepime Pharmacokinetics in Critically Ill Pediatric Patients Receiving Continuous Renal Replacement Therapy
Gideon Stitt, Jennifer Morris, Lindsay Schmees, Joseph Angelo, Ayse Akcan Arikan
Antimicrobial Agents and Chemotherapy Mar 2019, 63 (4) e02006-18; DOI: 10.1128/AAC.02006-18
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KEYWORDS

intensive care units
pediatrics
pharmacodynamics
pharmacokinetics
renal replacement therapy

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