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Pharmacology

Pharmacokinetics of Cefepime during Continuous Renal Replacement Therapy in Critically Ill Patients

Rebecca S. Malone, Douglas N. Fish, Edward Abraham, Isaac Teitelbaum
Rebecca S. Malone
Department of Pharmacy Practice and Science, University of Arizona Health Sciences Center, Tucson, Arizona, and
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Douglas N. Fish
Department of Pharmacy Practice,
Division of Pulmonary Sciences and Critical Care Medicine, and
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Edward Abraham
Division of Pulmonary Sciences and Critical Care Medicine, and
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Isaac Teitelbaum
Division of Renal Diseases and Hypertension, University of Colorado Health Sciences Center, Denver, Colorado
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DOI: 10.1128/AAC.45.11.3148-3155.2001
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    Fig. 1.

    Mean concentrations of cefepime in serum with various dosage regimens during CVVH and CVVHDF. The cefepime concentrations are shown in micrograms per milliliter. The x axis represents postinfusion times. Error bars represent standard deviations.

Tables

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  • Table 1.

    Demographic and clinical characteristics of the 12 study patients

    PatientAge (yr)Ht (cm)Wt (kg)SexaAPACHE II scorebPrincipal diagnosis(es)Infectious diagnosisIsolated pathogen (MIC [μg/ml])Outcome
    15516671.0F30End-stage liver diseaseFUOcNoneDied
    248183107.4M27End-stage liver diseasePneumoniaP. aeruginosa (4),Enterobacter cloacae (1)Died
    34216988.4M25End-stage liver diseaseIntra-abdominal sepsisNoneSurvived
    45418289.0M31End-stage heart disease, sepsisPneumoniaNoneDied
    53416899.9F23Idiopathic thrombocytopenia purpura, respiratory failurePneumoniaKlebsiella pneumoniae (1), Moraxella catarrhalis (0.03)Survived
    66317399.3M29Congestive heart failure, cardiogenic shockPneumoniaKlebsiella oxytoca(0.125)Survived
    75917882.2M24End-stage liver disease, sepsisIntra-abdominal sepsisEscherichia coli (0.03)Died
    841178133.8M32Thoracic aortic dissectionPneumoniaNoneSurvived
    933173108.0F26End-stage heart diseaseFUONoneSurvived
    1070204125.3F29Sepsis, rhabdomyolysisCellulitisGroup B streptococci (0.25)Survived
    1173172136.0M28Intra-abdominal sepsisIntra-abdominal sepsisNoneSurvived
    125217082.8M29Congestive heart failure, cardiogenic shockPneumoniaE. coli (0.06),Haemophilus influenzae (0.016)Survived
    • ↵a F, female; M, male.

    • ↵b APACHE II score, Acute Physiology and Chronic Health Evaluation II score on admission to the intensive care unit.

    • ↵c FUO, fever of unknown origin.

  • Table 2.

    Etiologies of renal failure and details of CRRT

    PatientEtiology of renal failureaUrine output/ 24 h (ml)bType of CRRTBlood flow rate (ml/min)bDialysis rate (ml/h)b, c, dUltrafiltration rate (ml/min)b, dConcomitant vasoactive drug(s)
    1Ischemic ATN0CVVH15019 ± 2Dopamine
    2ATN 2° unknown etiology134CVVH1509 ± 8None
    3Hepatorenal syndrome12CVVH15019 ± 4Dopamine
    4Sepsis with MODS155CVVH15015 ± 2Dopamine, norepinephrine
    5Idiopathic thrombocytopenia purpura35CVVH15017 ± 12None
    6Cardiogenic shock0CVVHDF150957 ± 8118 ± 2Dopamine, isoproteranol
    7Sepsis with MODS29CVVHDF150857 ± 22720 ± 10Norepinephrine
    8Ischemic ATN0CVVHDF150940 ± 2814 ± 1Dopamine, norepinephrine
    9ATN 2° unknown etiology0CVVHDF150954 ± 4720 ± 4Epinephrine
    10Rhabdomyolysis67CVVHDF150970 ± 16123 ± 7None
    11ATN 2° sepsis with MODS43CVVHDF1501,000 ± 013 ± 2Dopamine, norepinephrine
    12Cardiogenic shock0CVVHDF1501,020 ± 2614 ± 2Dopamine, epinephrine
    • ↵a ATN, acute tubular necrosis; 2°, secondary; MODS, multiple-organ dysfunction syndrome.

    • ↵b During time of pharmacokinetic sampling.

    • ↵c Applicable only to patients receiving CVVHDF.

    • ↵d Rates shown as means ± standard deviations.

  • Table 3.

    Summary of cefepime pharmacokinetic parameters for patients receiving CVVH

    PatientDosing regimenCmax(μg/ml)Cmin(μg/ml)AUC0–24(μg · h/ml)t1/2 (h)V (liter/kg)CLSUFRa (ml/min)CRRT CLbSb
    ml/minml/min/kgml/minml/min/kg%CLS
    12 g every 24 h61.618.7943.513.70.6438 ± 60.54 ± 0.0819 ± 216 ± 40.23 ± 0.0542 ± 30.92 ± 0.07
    22 g every 24 h67.413.51,050.910.20.3644 ± 40.41 ± 0.049 ± 83 ± 20.03 ± 0.028 ± 40.84 ± 0.05
    32 g every 24 h86.420.71,258.411.40.3833 ± 40.38 ± 0.0419 ± 417 ± 30.19 ± 0.0429 ± 190.89 ± 0.08
    41 g every 12 h44.627.9834.717.00.4328 ± 30.29 ± 0.0315 ± 213 ± 30.13 ± 0.0345 ± 140.81 ± 0.13
    52 g every 12 h94.948.01,677.812.20.3835 ± 10.36 ± 0.0117 ± 1214 ± 100.14 ± 0.1039 ± 280.83 ± 0.11
    Mean ± SD12.9 ± 2.60.46 ± 0.1436 ± 6c0.40 ± 0.09c16 ± 4a13 ± 4a0.15 ± 0.06c40 ± 16c0.86 ± 0.04c
    • ↵a UFR, ultrafiltration rate.

    • ↵b Values are means ± standard deviations calculated from parameter values determined during each of the four or five postdose sampling intervals for each patient: 1 to 2 h, 2 to 4 h, 4 to 8 h, 8 to 12 h, and 12 to 24 h (except with 12-h dosing interval regimens).

    • ↵c Means ± standard deviations calculated from means of the four or five parameter values determined for each individual patient.

  • Table 4.

    Summary of cefepime pharmacokinetic parameters for patients receiving CVVHDF

    PatientDosing regimenCmax(μg/ml)Cmin(μg/ml)AUC0–24(μg · h/ml)t1/2 (h)V (liter/kg)CLSUFRa (ml/min)CRRT CLbSab
    ml/minml/min/kgml/minml/min/kg%CLS
    61 g every 24 h44.85.8600.78.00.3038 ± 40.44 ± 0.0418 ± 225 ± 60.28 ± 0.0733 ± 100.73 ± 0.09
    71 g every 24 h25.73.5344.98.20.5867 ± 50.81 ± 0.0620 ± 1023 ± 80.27 ± 0.1066 ± 180.65 ± 0.09
    81 g every 12 h36.213.6581.88.30.3558 ± 10.49 ± 0.0114 ± 128 ± 10.24 ± 0.0248 ± 10.92 ± 0.02
    92 g every 24 h72.910.4979.28.40.3226 ± 60.24 ± 0.0620 ± 447 ± 50.44 ± 0.0556 ± 140.73 ± 0.12
    102 g every 24 h79.16.91,009.96.70.2136 ± 80.30 ± 0.0723 ± 745 ± 20.37 ± 0.0181 ± 190.93 ± 0.06
    112 g every 24 h63.612.2890.99.90.2623 ± 20.17 ± 0.0113 ± 242 ± 10.31 ± 0.0153 ± 40.78 ± 0.07
    122 g every 24 h90.820.41,306.810.90.3422 ± 10.27 ± 0.0214 ± 230 ± 10.36 ± 0.0176 ± 40.75 ± 0.05
    Mean ± SD8.6 ± 1.40.34 ± 0.1247 ± 0.12c0.46 ± 0.17c17 ± 4c26 ± 5c0.25 ± 0.04c59 ± 16c0.78 ± 0.10c
    • ↵a UFR, ultrafiltration rate.

    • ↵b Values are means ± standard deviations calculated from parameter values determined during each of the four or five postdose sampling intervals for each patient: 1 to 2 h, 2 to 4 h, 4 to 8 h, 8 to 12 h, and 12 to 24 h (except with 12-h dosing interval regimens).

    • ↵c Means ± standard deviations calculated from means of the four or five parameter values determined for each individual patient.

  • Table 5.

    Calculated pharmacodynamic parameters for cefepime with various dosage regimens during CRRT

    Pharmacodynamic parameterParameter value by different dosage regimens and treatments
    1 g every 24 h1 g every 12 h2 g every 24 h2 g every 12 h
    CVVHCVVHDF (n = 2)CVVH (n = 1)CVVHDF (n = 1)CVVH (n = 3)CVVHDF (n = 4)CVVH (n = 1)CVVHDF
    T > MICNAaNA
     MIC ≤ 4 μg/mlNA100%100%100%100%100%100%NA
     MIC = 8 μg/mlNA74%100%100%100%100%100%NA
     MIC = 16 μg/mlNA40%100%85%100%84%100%NA
    AUC0–24/MIC
     MIC ≤ 4 μg/mlNA118209145263262419NA
     MIC = 8 μg/mlNA5910473131131210NA
     MIC = 16 μg/mlNA3052366665105NA
    • ↵a NA, not available (dosage regimens not studied).

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Pharmacokinetics of Cefepime during Continuous Renal Replacement Therapy in Critically Ill Patients
Rebecca S. Malone, Douglas N. Fish, Edward Abraham, Isaac Teitelbaum
Antimicrobial Agents and Chemotherapy Nov 2001, 45 (11) 3148-3155; DOI: 10.1128/AAC.45.11.3148-3155.2001

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Pharmacokinetics of Cefepime during Continuous Renal Replacement Therapy in Critically Ill Patients
Rebecca S. Malone, Douglas N. Fish, Edward Abraham, Isaac Teitelbaum
Antimicrobial Agents and Chemotherapy Nov 2001, 45 (11) 3148-3155; DOI: 10.1128/AAC.45.11.3148-3155.2001
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KEYWORDS

cephalosporins
hemofiltration
Kidney Failure, Chronic

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