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Susceptibility

In Vitro Antifungal Susceptibility Testing of Candida Isolates with the EUCAST Methodology, a New Method for ECOFF Determination

J. Meletiadis, I. Curfs-Breuker, J. F. Meis, J. W. Mouton
J. Meletiadis
aClinical Microbiology Laboratory, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
bDepartment of Medical Microbiology and Infectious Diseases, Erasmus Medical Center, Rotterdam, The Netherlands
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I. Curfs-Breuker
cDepartment of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands
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J. F. Meis
cDepartment of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands
dCenter of Expertise in Mycology, Radboudumc, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands
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J. W. Mouton
bDepartment of Medical Microbiology and Infectious Diseases, Erasmus Medical Center, Rotterdam, The Netherlands
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DOI: 10.1128/AAC.02372-16
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    FIG 1

    Examples of the derivatization method used with two previously published distributions of voriconazole. (Left) MIC distributions. ECOFFs were determined using the eyeball method. (Right) Second derivatives as functions of the MIC. ECOFFs were determined using the derivatization method. Inflection points, maximum second derivatives, and hypothetical MIC subpopulations are indicated.

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  • TABLE 1

    EUCAST clinical breakpoints and epidemiological cutoff values

    DrugClinical breakpoints and ECOFFs for isolates from indicated strains (mg/liter)a
    C. albicansC. parapsilosisC. kruseiC. glabrataC. tropicalis
    BPECOFFdECOFFBPECOFFdECOFFBPECOFFdECOFFBPECOFFdECOFFBPECOFFdECOFF
    Amphotericin B112112112112112
    Fluconazole2/4112/422–b12816/256d0.002/3232322/421
    Itraconazole0.060.060.030.120.120.06IEc11 220.120.120.06
    Voriconazole0.120.120.030.120.120.03IE11 110.120.120.06
    Posaconazole0.060.060.030.060.060.03IE0.50.5 110.060.060.06
    Anidulafungin0.030.030.060.002/4440.060.060.060.060.060.060.060.060.06
    Micafungin0.0160.0160.030.002/424IE0.250.250.030.030.06IE0.060.06
    • ↵a BP, breakpoint (S≤/R>). dECOFFs were determined in this study using the derivatization method applied to the MIC distributions on the EUCAST website.

    • ↵b Susceptibility testing is not recommended, as the species is a poor target for therapy with the drug.

    • ↵c Insufficient evidence to determine a breakpoint.

    • ↵d The two maximum 2nd derivatives are at MIC 16 to 256 mg/liter and represent a resistant population.

  • TABLE 2

    MIC distribution for each drug and Candida species in this study

    SpeciesDrugNo. of isolates showing resistance to indicated drug at an MIC (mg/liter) of:MIC50MIC90Rb
    >32321684210.50.250.1250.0630.0310.0160.0080.004
    C. albicans (n = 584)Amphotericin B 293461991 0.50.50.0
    Fluconazole4 31133543861263 0.250.51.4
    Itraconazole 122649524 ≤0.0160.03150.9
    Voriconazole 122 144570 ≤0.016≤0.0167.0
    Posaconazole 155139434 ≤0.0160.03151.0
    Anidulafungin 3133448 ≤0.0080.0160.0
    Micafungin 312431691620.0080.0160.7
    C. tropicalis (n = 180)Amphotericin B 172116 0.511.1
    Fluconazole 11371671 0.50.51.2
    Itraconazole 11219859 0.0310.0620.6
    Voriconazole 13147983 0.0310.0310.6
    Posaconazole 2321388 0.0310.0631.1
    Anidulafungin 1 12177782 0.0310.0631.1
    Micafungin 3218967 0.0310.0631.7
    C. parapsilosis (n = 122)aAmphotericin B 8636 110.0
    Fluconazole 2823744488 149.8
    Itraconazole 17465612 0.0310.0630.8
    Voriconazole 21383366 ≤0.0160.1252.7
    Posaconazole 57641 0.0630.0635.8
    Anidulafungin 33881 120.0
    Micafungin 15566 120.0
    C. glabrata (n = 86)Amphotericin B 274613 0.510.0
    Fluconazole213539315 482.3
    Itraconazole 1 183725113 0.250.51.2
    Voriconazole 1 1283539 0.1250.251.7
    Posaconazole 1 1 239376 0.1250.252.3
    Anidulafungin 115241 0.0310.0630.0
    Micafungin 9591260.0160.03150.0
    C. krusei (n = 30)Amphotericin B 237 110.0
    Fluconazole9174 32>64100
    Itraconazole 3121131 0.1250.250.0
    Voriconazole 48162 0.2510.0
    Posaconazole 61671 0.1250.250.0
    Anidulafungin 1263 0.0630.0633.3
    Micafungin 8211 0.1250.250.0
    Candida spp. (n = 97)Amphotericin B 20531842 0.51ND
    Fluconazole 1172015922193 14ND
    Itraconazole 71415143413 0.0630.25ND
    Voriconazole 712161250 ≤0.0160.125ND
    Posaconazole 11126251915 0.0630.25ND
    Anidulafungin 1 192017221512612 0.252ND
    Micafungin 1 201712168149 0.251ND
    • ↵a The MIC90s of fluconazole, voriconazole, and echinocandins were 1 2-fold dilution higher for C. parapsilosissensu stricto than for sibling species.

    • ↵b Percent of resistant or non-wild-type isolates.

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In Vitro Antifungal Susceptibility Testing of Candida Isolates with the EUCAST Methodology, a New Method for ECOFF Determination
J. Meletiadis, I. Curfs-Breuker, J. F. Meis, J. W. Mouton
Antimicrobial Agents and Chemotherapy Mar 2017, 61 (4) e02372-16; DOI: 10.1128/AAC.02372-16

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In Vitro Antifungal Susceptibility Testing of Candida Isolates with the EUCAST Methodology, a New Method for ECOFF Determination
J. Meletiadis, I. Curfs-Breuker, J. F. Meis, J. W. Mouton
Antimicrobial Agents and Chemotherapy Mar 2017, 61 (4) e02372-16; DOI: 10.1128/AAC.02372-16
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KEYWORDS

antifungal agents
Candida
microbial sensitivity tests
Candida
EUCAST
antifungal susceptibility testing
epidemiological cutoff value

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