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Experimental Therapeutics

Activities of Sordarins in Murine Histoplasmosis

John R. Graybill, Laura Najvar, Annette Fothergill, Rosie Bocanegra, Federico Gomez de las Heras
John R. Graybill
University of Texas Health Science Center and
Veterans Administration Hospital, San Antonio, Texas, and
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Laura Najvar
University of Texas Health Science Center and
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Annette Fothergill
Veterans Administration Hospital, San Antonio, Texas, and
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Rosie Bocanegra
University of Texas Health Science Center and
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Federico Gomez de las Heras
Glaxo Wellcome SA, Tres Cantos, Madrid, Spain
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DOI: 10.1128/AAC.43.7.1716
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Tables

  • Table 1.

    Mean days of survival of mice infected withH. capsulatuma

    Drug or treatmentDose (mg/kg)No. of days of survivalNo. alive after 30 days
    MeanSEM
    ControlNone 9.52.41
    GM15027.7b2.58
    1025.2b3.17
    GM25025.7b3.58
    1028.4b2.69
    GM35030b0.39
    1030b010
    • ↵a Mice were infected intravenously with 1.2 × 107 CFU of H. capsulatum, treated from day 2 through 8, and observed for their rate of survival through day 30. Ten mice were in each treatment group.

    • ↵b P < 0.001 compared with the control group.

  • Table 2.

    Survival of mice infected intravenously withH. capsulatuma

    Study and inoculum (CFU)Drug or treatmentDose (mg/kg)No. of days of survivalNo. alive at day 30
    MeanSEM
    Study A (2.0 × 106)ControlNone15.22.92
    GM22030b010
    1028.4b2.69
    529.1b1.99
    230b010
    Amphotericin B130b010
    0.530b010
    Fluconazole1023.24.07
    520.13.75
    Study B (108)ControlNone 4.00.140
    GM35 6.7b0.90
    1.25 4.90.40
    0.3 4.00.30
    0.06 4.10.20
    Amphotericin B1.2528.4b2.69
    0.3 4.80.20
    Fluconazole1013.1b3.22
    • ↵a Mice were treated from day 2 through 8 after infection, and their rates of survival were observed through day 30. Ten mice were in each treatment group.

    • ↵b P < 0.001 compared with the control group.

  • Table 3.

    Lung and kidney tissue burdensa

    TissueDrug or treatmentDose (mg/kg)Mean burden95% CINo. of mice with counts of <20 CFU/g
    LowerUpper
    KidneyControlNone2.3 × 1071.2 × 1075.7 × 1070
    GM3104.8 × 104 b2.5 × 1041.2 × 1050
    58.0 × 105 b4.3 × 1052.0 × 1060
    1.251.3 × 1086.9 × 1073.2 × 1080
    Amphotericin B2.52.3 × 102 c1.2 × 1025.7 × 1023
    Fluconazole53.4 × 106 b1.8 × 1068.3 × 1060
    LungControlNone5.9 × 1073.1 × 1071.6 × 1081
    GM3101.1 × 105 b5.7 × 1042.6 × 1050
    52.9 × 106 b1.5 × 1067.8 × 1061
    1.251.9 × 1081.0 × 1084.8 × 1080
    Amphotericin B2.51.2 × 102 c6.7 × 1013.1 × 1026
    Fluconazole51.3 × 107 b6.8 × 1063.1 × 1070
    • ↵a Values are expressed as CFU per gram of tissue. Each treatment group consisted of seven mice. CI, confidence interval.

    • b P < 0.05 compared with control group.

    • c P < 0.01 compared with control group or groups receiving fluconazole or GM3.

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Activities of Sordarins in Murine Histoplasmosis
John R. Graybill, Laura Najvar, Annette Fothergill, Rosie Bocanegra, Federico Gomez de las Heras
Antimicrobial Agents and Chemotherapy Jul 1999, 43 (7) 1716-1718; DOI: 10.1128/AAC.43.7.1716

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Activities of Sordarins in Murine Histoplasmosis
John R. Graybill, Laura Najvar, Annette Fothergill, Rosie Bocanegra, Federico Gomez de las Heras
Antimicrobial Agents and Chemotherapy Jul 1999, 43 (7) 1716-1718; DOI: 10.1128/AAC.43.7.1716
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KEYWORDS

antifungal agents
Histoplasmosis

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