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Susceptibility

In Vitro Activities of Posaconazole, Fluconazole, Itraconazole, Voriconazole, and Amphotericin B against a Large Collection of Clinically Important Molds and Yeasts

F. Sabatelli, R. Patel, P. A. Mann, C. A. Mendrick, C. C. Norris, R. Hare, D. Loebenberg, T. A. Black, P. M. McNicholas
F. Sabatelli
Schering-Plough Research Institute, Kenilworth, New Jersey
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R. Patel
Schering-Plough Research Institute, Kenilworth, New Jersey
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P. A. Mann
Schering-Plough Research Institute, Kenilworth, New Jersey
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C. A. Mendrick
Schering-Plough Research Institute, Kenilworth, New Jersey
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C. C. Norris
Schering-Plough Research Institute, Kenilworth, New Jersey
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R. Hare
Schering-Plough Research Institute, Kenilworth, New Jersey
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D. Loebenberg
Schering-Plough Research Institute, Kenilworth, New Jersey
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T. A. Black
Schering-Plough Research Institute, Kenilworth, New Jersey
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P. M. McNicholas
Schering-Plough Research Institute, Kenilworth, New Jersey
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  • For correspondence: paul.mcnicholas@spcorp.com
DOI: 10.1128/AAC.00163-06
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Tables

  • TABLE 1.

    In vitro activities of posaconazole, itraconazole, fluconazole, voriconazole, and amphotericin B against all fungi, molds, and yeasts tested

    Antifungal agentIn vitro activity againsta:
    All fungiAll moldsAll yeasts
    nMIC (μg/ml)nMIC (μg/ml)nMIC (μg/ml)
    50%90%50%90%50%90%
    POS22,8500.0631.04,4990.1251.018,3510.0631.0
    ITC18,8770.1251.03,2040.54.015,6730.1251.0
    FLC17,8840.5128.01,779256.0256.016,1050.516.0
    VRC9,5980.0310.51,8260.252.07,7720.0310.5
    AMB16,5671.01.03,0131.02.013,5541.01.0
    • ↵ a n is the number of MICs determined. 50% and 90%, MIC50 and MIC90, respectively.

  • TABLE 2.

    Comparative in vitro activities of posaconazole, itraconazole, voriconazole, and amphotericin B against mold isolates

    OrganismNo. of MICsMIC (μg/ml)a
    POSITCVRCAMB
    50%90%50%90%50%90%50%90%
    All molds1,7020.251.00.52.00.252.00.52.0
    All hyaline moldsb1,6360.251.00.5c2.0c0.251.00.52.0
    All Aspergillus spp.1,4230.1250.50.52.00.250.50.51.0
        A. flavus890.250.50.51.00.51.01.02.0
        A. fumigatus1,1190.1250.50.51.00.250.50.51.0
        A. niger1010.250.51.02.00.52.00.1251.0
        A. terreus220.250.250.50.50.250.52.02.0
        Other Aspergillus spp.d920.1251.00.52.00.251.01.02.0
    All zygomycetes860.54.01.032.016.0128.00.252.0
        Rhizopus spp.321.08.04.032.016.0128.01.02.0
        Mucor spp.181.016.02.032.064.0128.00.251.0
        Absidia spp.160.1250.250.1250.516.0128.00.250.5
        Cunninghamella spp.60.031-1.00.031-1.00.125-2.00.125-2.08.0-128.08.0-128.00.125-2.00.125-2.0
        Apophysomyces spp.50.031-4.00.031-4.00.031-8.00.031-8.016.0-128.016.0-128.00.031-4.00.031-4.0
        Saksenaea spp.40.016-2.00.016-2.00.016-0.1250.016-0.1250.5-4.00.5-4.00.063-0.50.063-0.5
        Rhizomucor spp.30.016-0.250.016-0.250.016-0.250.016-0.252.0-16.02.0-16.00.063-0.1250.063-0.125
        Cokeromyces spp.20.25-4.00.25-4.00.25-8.00.25-8.016.0-64.016.0-64.00.125-0.50.125-0.5
    All dimorphic fungi1510.0630.250.0310.25NDND0.250.5
        Histoplasma spp.530.0190.250.0190.063NDND0.250.5
        Blastomyces spp.380.0630.1250.0312.0NDND0.1250.5
        Coccidioides spp.250.1250.250.1250.25NDND0.50.5
        Paracoccidioides spp.130.0630.1250.0160.063NDND0.1250.25
        Penicillium marneffei120.0160.0160.0080.063NDND0.54.0
        Sporothrix spp.100.51.00.250.5NDND0.51.0
    All Fusarium spp.6716.032.016.0e32.0e16.032.08.032.0
        F. solani3932.032.0NDND16.032.016.032.0
        F. oxysporum122.04.0NDND4.032.08.016.0
        F. moniliforme21.01.0NDND1.01.01.0-4.01.0-4.0
        Other Fusarium spp.f1416.016.0NDND4.016.01.02.0
    Agents of chromoblastomycosis, mycetoma, and phaeohyphomycosis2410.2516.01.064.0NDND2.032.0
        Scedosporium prolificans8016.032.064.064.0NDND16.032.0
        Scedosporium apiospermum260.251.01.032.0NDND2.08.0
        Pseudallescheria spp.410.251.00.51.0NDND2.04.0
        Aspergillus nidulans200.0630.250.250.5NDND1.02.0
        Exophiala spp.140.250.50.51.0NDND0.51.0
        Alternaria spp.130.1250.250.51.0NDND0.54.0
        Cladosporium spp.110.06316.00.12516.0NDND1.04.0
        Bipolaris spp.100.0630.1250.0630.25NDND0.250.25
        Otherg260.1250.250.251.0NDND0.51.0
    Other moldsh580.250.50.0631.00.250.50.252.0
    • ↵ a 50% and 90%, MIC50 and MIC90, respectively. When n is <10, the MICs shown are ranges. ND, not determined.

    • ↵ b Includes Aspergillus spp. and Fusarium spp. (MIC data for which are shown below), and other various species, including strains of Acremonium, Basidiomycetes, Bjerkandera, Coprinus, Paecilomyces, Pseudallescheria, and Schizophyllum.

    • ↵ c Fewer isolates (n = 1,501) were tested against ITC; therefore, the values for ITC cannot be compared directly.

    • ↵ d Includes strains of A. glaucus, A. nidulans, A. oryzae, Aspergillus spp., A. sydowii, A. ustus, and A. versicolor.

    • ↵ e Fewer isolates (n = 23) were tested against ITC; therefore, the values for ITC cannot be compared directly.

    • ↵ f Unspeciated Fusarium.

    • ↵ g Includes strains of Cladophialophora, Curvularia, Exserohilum, Fonsecaea, Pithomyces, Ramichloridium, Ulocladium, and Wangiella.

    • ↵ h Includes strains of Acremonium, Basidiomycetes, Bjerkandera, Coprinus, Paecilomyces, Pseudallescheria, Schizophyllum, and Trichophyton.

  • TABLE 3.

    Comparative in vitro activities of posaconazole, itraconazole, and fluconazole against isolates of dermatophytes

    OrganismNo. of MICsMIC (μg/ml)a
    POSITCFLC
    50%90%50%90%50%90%
    All dermatophytes1800.0310.250.0630.254.064.0
    Trichophyton rubrum 910.0630.1250.0630.252.032.0
    T. mentagrophytes 290.0160.1250.0310.258.064.0
    T. tonsurans 230.0310.250.0310.0634.032.0
    Other Trichophyton spp.b50.063-0.50.063-0.50.031-4.00.031-4.01.0-128.01.0-128.0
    Microsporum spp.c160.0160.1250.0160.52.0128.0
    Epidermophyton floccosum 150.0160.250.0160.252.02.0
    Arthroderma benhamiae 10.0310.0310.0310.0311.01.0
    • ↵ a 50% and 90%, MIC50 and MIC90, respectively. When n is <10, the MICs shown are ranges.

    • ↵ b Includes strains of T. krajdeneii, T. raubitschekii, T. soudanense, and T. terrestre.

    • ↵ c Includes strains of M. canis, M. gypseum, and M. persicolor.

  • TABLE 4.

    Comparative in vitro activities of posaconazole, itraconazole, fluconazole, voriconazole, and amphotericin B against isolates of Candida spp. and Cryptococcus spp.

    OrganismNo. of MICsMIC (μg/ml)a
    POSITCFLCVRCAMB
    50%90%50%90%50%90%50%90%50%90%
    All Candida spp.6,9650.0631.00.1251.00.516.00.0310.51.0b1.0b
        C. albicans3,5350.0310.0630.0630.250.252.00.0080.0631.0b1.0b
        C. glabrata1,2181.02.01.04.08.064.00.252.01.0b1.0b
        C. parapsilosis9700.0630.250.250.51.04.00.0310.1251.01.0
        C. tropicalis7190.0630.250.1250.51.04.00.0630.51.01.0
        C. krusei1890.51.01.01.032.064.00.250.51.02.0
        C. lusitaniae840.0630.250.252.01.04.00.0310.0631.02.0
        C. guilliermondii260.251.00.54.04.032.00.0638.00.51.0
        C. dubliniensis1640.0310.1250.0630.50.2532.00.0160.1250.51.0
        Other Candida spp.c600.252.00.51.04.016.00.0630.251.01.0
    Cryptococcus spp.d2710.1250.250.1250.54.08.00.0630.1251.01.0
    • ↵ a 50% and 90%, MIC50 and MIC90, respectively.

    • ↵ b The number of strains of C. albicans and C. glabrata tested against AMB was slightly less (for all Candida spp., n = 6,921; for C. albicans, n = 3,517; and for C. glabrata, n = 1,192).

    • ↵ c Includes strains of C. famata, C. kefyr, C. lipolytica, C. pelliculosa, C. pseudotropicalis, C. rugosa, C. sphaerica, C. stellatoidea, and C. zeylanoides.

    • ↵ d Includes strains of C. laurentii and C. neoformans.

  • TABLE 5.

    Comparative in vitro activities of posaconazole, itraconazole, fluconazole, and voriconazole, against isolates of Candida spp. exhibiting resistance to itraconazole, fluconazole, and voriconazole

    Isolates (resistance level)No. of MICsaMIC (μg/ml)b
    POSITCFLCVRC
    50%90%50%90%50%90%50%90%
    FLC resistant (MIC, >32 μg/ml)
        All Candida4461.016.02.032.0128.0256.02.032.0
        C. albicans1670.516.02.032.0128.0256.02.032.0
        C. glabrata1492.016.04.016.0256.0256.04.08.0
        Other Candida spp.1300.54.01.032.0128.0128.00.532.0
    ITC resistant (MIC, >0.5 μg/ml)
        All Candida1,1511.04.01.016.016.0128.00.54.0
        C. albicans1761.016.04.032.064.0256.02.032.0
        C. glabrata7191.04.01.08.016.0128.00.54.0
        Other Candida spp.2560.52.01.08.032.0128.00.516.0
    VRC resistant (MIC, >2 μg/ml)
        All Candida2344.016.08.032.0128.0256.08.032.0
        C. albicans1012.016.08.032.0128.0256.08.032.0
        C. glabrata884.016.016.032.0128.0256.04.016.0
        Other Candida spp.452.032.02.032.0128.0128.032.032.0
    With POS MIC of >2 μg/ml
        All Candida1768.032.016.032.0128.0256.04.032.0
        C. albicans628.032.016.032.0128.0256.016.064.0
        C. glabrata868.016.016.032.0128.0256.04.08.0
        Other Candida spp.2816.032.08.032.0128.0128.032.032.0
    • ↵ a The data set is the same as that used in Table 4. There were a total of 6,595 MICs for all four drugs.

    • ↵ b 50% and 90%, MIC50 and MIC90, respectively.

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In Vitro Activities of Posaconazole, Fluconazole, Itraconazole, Voriconazole, and Amphotericin B against a Large Collection of Clinically Important Molds and Yeasts
F. Sabatelli, R. Patel, P. A. Mann, C. A. Mendrick, C. C. Norris, R. Hare, D. Loebenberg, T. A. Black, P. M. McNicholas
Antimicrobial Agents and Chemotherapy May 2006, 50 (6) 2009-2015; DOI: 10.1128/AAC.00163-06

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In Vitro Activities of Posaconazole, Fluconazole, Itraconazole, Voriconazole, and Amphotericin B against a Large Collection of Clinically Important Molds and Yeasts
F. Sabatelli, R. Patel, P. A. Mann, C. A. Mendrick, C. C. Norris, R. Hare, D. Loebenberg, T. A. Black, P. M. McNicholas
Antimicrobial Agents and Chemotherapy May 2006, 50 (6) 2009-2015; DOI: 10.1128/AAC.00163-06
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KEYWORDS

amphotericin B
antifungal agents
Aspergillus
Candida
Cryptococcus

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