Experimental Therapeutics

Daptomycin Dose-Effect Relationship against Resistant Gram-Positive Organisms

Raymond Cha, Richard G. Grucz Jr., Michael J. Rybak
DOI: 10.1128/AAC.47.5.1598-1603.2003

Article Figures & Data

Figures

  • FIG. 1.
    FIG. 1.

    Pharmacodynamic time-kill analysis of MRSA-67. GC, growth control; D1 through D6, daptomycin at dose regimens ranging from 1 to 6 mg/kg every 24 h.

  • FIG. 2.
    FIG. 2.

    Pharmacodynamic time-kill analysis of GISA-992. GC, growth control; D2 through D8, daptomycin at dose regimens simulating 2 to 8 mg/kg every 24 h.

  • FIG. 3.
    FIG. 3.

    Pharmacodynamic time-kill analysis of VREF-12366. GC, growth control; D3 through D9, daptomycin at dose regimens simulating 3 to 9 mg/kg every 24 h.

  • FIG. 4.
    FIG. 4.

    Pharmacokinetic-pharmacodynamic dose modeling to effect for MRSA isolates. ED50, dose correlating to 50% bacterial density reduction from growth control; ED80, dose correlating to 80% bacterial density reduction from growth control. •, MRSA-67 bacterial densities at 48 h; ○, MRSA-R515 bacterial densities at 48 h.

  • FIG. 5.
    FIG. 5.

    Pharmacokinetic-pharmacodynamic dose modeling to effect for GISA isolates. ED50, dose correlating to 50% bacterial density reduction from growth control; ED80, dose correlating to 80% bacterial density reduction from growth control. •, GISA-992 bacterial densities at 48 h; ○, GISA-147398 bacterial densities at 48 h.

  • FIG. 6.
    FIG. 6.

    Pharmacokinetic-pharmacodynamic dose modeling to effect for VREF isolates. ED50, dose correlating to 50% bacterial density reduction from growth control; ED80, dose correlating to 80% bacterial density reduction from growth control. •, VREF-12366 bacterial densities at 48 h; ○, VREF-SF12047 bacterial densities at 48 h.

Tables

  • TABLE 1.

    Results of pharmacokinetic analyses

    Dosing regimen (mg/kg)No. of simulationsParametera
    Cp-free (μg/ml)Ct-free (μg/ml)AUC24-free (μg · h/ml)
    1.0040.91 ± 0.040.12 ± 0.0211 ± 2.1
    1.5041.56 ± 0.020.17 ± 0.0113 ± 1.4
    2.00121.82 ± 0.050.22 ± 0.0318 ± 2.8
    2.5042.41 ± 0.110.29 ± 0.0322 ± 4.5
    3.00122.94 ± 0.210.37 ± 0.0726 ± 2.8
    3.5043.22 ± 0.190.41 ± 0.0531 ± 3.7
    4.00123.61 ± 0.070.45 ± 0.0235 ± 5.0
    5.00124.58 ± 0.220.60 ± 0.0741 ± 7.3
    5.5025.20 ± 0.150.65 ± 0.0544 ± 8.9
    6.00125.95 ± 0.190.73 ± 0.0947 ± 12.5
    6.5026.22 ± 0.110.76 ± 0.1150 ± 8.1
    7.0086.60 ± 0.140.85 ± 0.0756 ± 9.2
    8.0087.42 ± 0.290.90 ± 0.1062 ± 16.2
    9.0048.51 ± 0.131.05 ± 0.1181 ± 11.0

    • ↵ a C p-free, free peak concentration; Ct-free, free trough concentration. Values are presented as means ± standard deviations for all simulations.

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KEYWORDS

Anti-Bacterial Agents
daptomycin
Gram-positive bacteria

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