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Susceptibility

Epidemiological Cutoffs and Cross-Resistance to Azole Drugs in Aspergillus fumigatus

Juan Luis Rodriguez-Tudela, Laura Alcazar-Fuoli, Emilia Mellado, Ana Alastruey-Izquierdo, Araceli Monzon, Manuel Cuenca-Estrella
Juan Luis Rodriguez-Tudela
Servicio de Micologia, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Majadahonda, Spain
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  • For correspondence: jlrtudela@isciii.es
Laura Alcazar-Fuoli
Servicio de Micologia, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Majadahonda, Spain
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Emilia Mellado
Servicio de Micologia, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Majadahonda, Spain
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Ana Alastruey-Izquierdo
Servicio de Micologia, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Majadahonda, Spain
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Araceli Monzon
Servicio de Micologia, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Majadahonda, Spain
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Manuel Cuenca-Estrella
Servicio de Micologia, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Majadahonda, Spain
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DOI: 10.1128/AAC.00156-08
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    FIG. 1.

    MIC distribution for itraconazole, voriconazole, ravuconazole, and posaconazole for all strains except those with an itraconazole MIC of ≥8 mg/liter.

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  • TABLE 1.

    Geometric means and ranges of MICs obtained at 24 and 48 h for A. fumigatus isolates susceptible and resistant to azole drugs

    Isolate type and mechanism of resistanceItraconazoleVoriconazoleRavuconazolePosaconazole
    GM (range)MIC90GM (range)MIC90GM (range)MIC90GM (range)MIC90
    Susceptible (n = 361)0.32 (0.06-2)0.50.53 (0.06-2)10.60 (0.06-2)10.08 (0.015-2)0.125
    Resistant (n = 32)
        G54 mutationa (n = 9)16 (16-16)0.42 (0.12-1)0.32 (0.12-1)1.6 (0.25-16)
        M220 mutationb (n = 6)16 (16-16)1.0 (0.5-2)1.85 (1-4)0.65 (0.25-2)
        TRc (n = 17)16 (16-16)3.7 (2-8)6.8 (4-16)0.68 (0.5-8)
    • ↵ a At position 54, nine strains had a substitution of glycine for valine (three), glutamic acid (three), arginine (one), or tryptophan (two).

    • ↵ b At position 220, six strains had a substitution of methionine for valine (three), lysine (one), threonine (one), or isoleucine (one).

    • ↵ c At position 98, 17 strains had a substitution of leucine for histidine and two copies of a 34-bp sequence in tandem in the promoter of the cyp51A gene were present.

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    • Supplemental file 1 - Supplemental table listing the A. fumigatus strains used in the study.
      Zipped MS Word document, 24K.
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Epidemiological Cutoffs and Cross-Resistance to Azole Drugs in Aspergillus fumigatus
Juan Luis Rodriguez-Tudela, Laura Alcazar-Fuoli, Emilia Mellado, Ana Alastruey-Izquierdo, Araceli Monzon, Manuel Cuenca-Estrella
Antimicrobial Agents and Chemotherapy Jun 2008, 52 (7) 2468-2472; DOI: 10.1128/AAC.00156-08

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Epidemiological Cutoffs and Cross-Resistance to Azole Drugs in Aspergillus fumigatus
Juan Luis Rodriguez-Tudela, Laura Alcazar-Fuoli, Emilia Mellado, Ana Alastruey-Izquierdo, Araceli Monzon, Manuel Cuenca-Estrella
Antimicrobial Agents and Chemotherapy Jun 2008, 52 (7) 2468-2472; DOI: 10.1128/AAC.00156-08
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KEYWORDS

antifungal agents
Aspergillus fumigatus
azoles

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