Multicenter Study of Method-Dependent Epidemiological Cutoff Values for Detection of Resistance in Candida spp. and Aspergillus spp. to Amphotericin B and Echinocandins for the Etest Agar Diffusion Method

A Espinel-Ingroff; M Arendrup; E Cantón; S Cordoba; E Dannaoui; J García-Rodríguez; G M Gonzalez; N P Govender; E Martin-Mazuelos; M Lackner; C Lass-Flörl; M J Linares Sicilia; M A Rodriguez-Iglesias; T Pelaez; R K Shields; G Garcia-Effron; J Guinea; M Sanguinetti; J Turnidge

doi:10.1128/aac.01792-16

Multicenter Study of Method-Dependent Epidemiological Cutoff Values for Detection of Resistance in Candida spp. and Aspergillus spp. to Amphotericin B and Echinocandins for the Etest Agar Diffusion Method

A Espinel-Ingroff, M Arendrup, E Cantón, S Cordoba, E Dannaoui, J García-Rodríguez, G M Gonzalez, N P Govender, E Martin-Mazuelos, M Lackner, C Lass-Flörl, M J Linares Sicilia, M A Rodriguez-Iglesias, T Pelaez, R K Shields, G Garcia-Effron, J Guinea, M Sanguinetti, J Turnidge

Department of Clinical Medicine

30 Citations (Scopus)

Abstract

Method-dependent Etest epidemiological cutoff values (ECVs) are not available for susceptibility testing of either Candida or Aspergillus species with amphotericin B or echinocandins. In addition, reference caspofungin MICs for Candida spp. are unreliable. Candida and Aspergillus species wild-type (WT) Etest MIC distributions (microorganisms in a species-drug combination with no detectable phenotypic resistance) were established for 4,341 Candida albicans, 113 C. dubliniensis, 1,683 C. glabrata species complex (SC), 709 C. krusei, 767 C. parapsilosis SC, 796 C. tropicalis, 1,637 Aspergillus fumigatus SC, 238 A. flavus SC, 321 A. niger SC, and 247 A. terreus SC isolates. Etest MICs from 15 laboratories (in Argentina, Europe, Mexico, South Africa, and the United States) were pooled to establish Etest ECVs. Anidulafungin, caspofungin, micafungin, and amphotericin B ECVs (in micrograms per milliliter) encompassing ≥97.5% of the statistically modeled population were 0.016, 0.5, 0.03, and 1 for C. albicans; 0.03, 1, 0.03, and 2 for C. glabrata SC; 0.06, 1, 0.25, and 4 for C. krusei; 8, 4, 2, and 2 for C. parapsilosis SC; and 0.03, 1, 0.12, and 2 for C. tropicalis The amphotericin B ECV was 0.25 μg/ml for C. dubliniensis and 2, 8, 2, and 16 μg/ml for the complexes of A. fumigatus, A. flavus, A. niger, and A. terreus, respectively. While anidulafungin Etest ECVs classified 92% of the Candida fks mutants evaluated as non-WT, the performance was lower for caspofungin (75%) and micafungin (84%) cutoffs. Finally, although anidulafungin (as an echinocandin surrogate susceptibility marker) and amphotericin B ECVs should identify Candida and Aspergillus isolates with reduced susceptibility to these agents using the Etest, these ECVs will not categorize a fungal isolate as susceptible or resistant, as breakpoints do.

Original language	English
Article number	e01792-16
Journal	Antimicrobial Agents and Chemotherapy
Volume	61
Issue number	1
Number of pages	10
ISSN	0066-4804
DOIs	https://doi.org/10.1128/aac.01792-16
Publication status	Published - Jan 2017

Keywords

Amphotericin B/pharmacology
Antifungal Agents/pharmacology
Aspergillus/drug effects
Candida/drug effects
Disk Diffusion Antimicrobial Tests
Drug Resistance, Fungal
Echinocandins/pharmacology
Europe
Latin America
South Africa
United States

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Espinel-Ingroff, A., Arendrup, M., Cantón, E., Cordoba, S., Dannaoui, E., García-Rodríguez, J., Gonzalez, G. M., Govender, N. P., Martin-Mazuelos, E., Lackner, M., Lass-Flörl, C., Linares Sicilia, M. J., Rodriguez-Iglesias, M. A., Pelaez, T., Shields, R. K., Garcia-Effron, G., Guinea, J., Sanguinetti, M., & Turnidge, J. (2017). Multicenter Study of Method-Dependent Epidemiological Cutoff Values for Detection of Resistance in Candida spp. and Aspergillus spp. to Amphotericin B and Echinocandins for the Etest Agar Diffusion Method. Antimicrobial Agents and Chemotherapy, 61(1), Article e01792-16 . https://doi.org/10.1128/aac.01792-16

Multicenter Study of Method-Dependent Epidemiological Cutoff Values for Detection of Resistance in Candida spp. and Aspergillus spp. to Amphotericin B and Echinocandins for the Etest Agar Diffusion Method. / Espinel-Ingroff, A; Arendrup, M; Cantón, E et al.
In: Antimicrobial Agents and Chemotherapy, Vol. 61, No. 1, e01792-16 , 01.2017.

Research output: Contribution to journal › Journal article › Research › peer-review

Espinel-Ingroff, A, Arendrup, M, Cantón, E, Cordoba, S, Dannaoui, E, García-Rodríguez, J, Gonzalez, GM, Govender, NP, Martin-Mazuelos, E, Lackner, M, Lass-Flörl, C, Linares Sicilia, MJ, Rodriguez-Iglesias, MA, Pelaez, T, Shields, RK, Garcia-Effron, G, Guinea, J, Sanguinetti, M & Turnidge, J 2017, 'Multicenter Study of Method-Dependent Epidemiological Cutoff Values for Detection of Resistance in Candida spp. and Aspergillus spp. to Amphotericin B and Echinocandins for the Etest Agar Diffusion Method', Antimicrobial Agents and Chemotherapy, vol. 61, no. 1, e01792-16 . https://doi.org/10.1128/aac.01792-16

Espinel-Ingroff A, Arendrup M, Cantón E, Cordoba S, Dannaoui E, García-Rodríguez J et al. Multicenter Study of Method-Dependent Epidemiological Cutoff Values for Detection of Resistance in Candida spp. and Aspergillus spp. to Amphotericin B and Echinocandins for the Etest Agar Diffusion Method. Antimicrobial Agents and Chemotherapy. 2017 Jan;61(1):e01792-16 . doi: 10.1128/aac.01792-16

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title = "Multicenter Study of Method-Dependent Epidemiological Cutoff Values for Detection of Resistance in Candida spp. and Aspergillus spp. to Amphotericin B and Echinocandins for the Etest Agar Diffusion Method",

abstract = "Method-dependent Etest epidemiological cutoff values (ECVs) are not available for susceptibility testing of either Candida or Aspergillus species with amphotericin B or echinocandins. In addition, reference caspofungin MICs for Candida spp. are unreliable. Candida and Aspergillus species wild-type (WT) Etest MIC distributions (microorganisms in a species-drug combination with no detectable phenotypic resistance) were established for 4,341 Candida albicans, 113 C. dubliniensis, 1,683 C. glabrata species complex (SC), 709 C. krusei, 767 C. parapsilosis SC, 796 C. tropicalis, 1,637 Aspergillus fumigatus SC, 238 A. flavus SC, 321 A. niger SC, and 247 A. terreus SC isolates. Etest MICs from 15 laboratories (in Argentina, Europe, Mexico, South Africa, and the United States) were pooled to establish Etest ECVs. Anidulafungin, caspofungin, micafungin, and amphotericin B ECVs (in micrograms per milliliter) encompassing ≥97.5% of the statistically modeled population were 0.016, 0.5, 0.03, and 1 for C. albicans; 0.03, 1, 0.03, and 2 for C. glabrata SC; 0.06, 1, 0.25, and 4 for C. krusei; 8, 4, 2, and 2 for C. parapsilosis SC; and 0.03, 1, 0.12, and 2 for C. tropicalis The amphotericin B ECV was 0.25 μg/ml for C. dubliniensis and 2, 8, 2, and 16 μg/ml for the complexes of A. fumigatus, A. flavus, A. niger, and A. terreus, respectively. While anidulafungin Etest ECVs classified 92% of the Candida fks mutants evaluated as non-WT, the performance was lower for caspofungin (75%) and micafungin (84%) cutoffs. Finally, although anidulafungin (as an echinocandin surrogate susceptibility marker) and amphotericin B ECVs should identify Candida and Aspergillus isolates with reduced susceptibility to these agents using the Etest, these ECVs will not categorize a fungal isolate as susceptible or resistant, as breakpoints do.",

keywords = "Amphotericin B/pharmacology, Antifungal Agents/pharmacology, Aspergillus/drug effects, Candida/drug effects, Disk Diffusion Antimicrobial Tests, Drug Resistance, Fungal, Echinocandins/pharmacology, Europe, Latin America, South Africa, United States",

author = "A Espinel-Ingroff and M Arendrup and E Cant{\'o}n and S Cordoba and E Dannaoui and J Garc{\'i}a-Rodr{\'i}guez and Gonzalez, {G M} and Govender, {N P} and E Martin-Mazuelos and M Lackner and C Lass-Fl{\"o}rl and {Linares Sicilia}, {M J} and Rodriguez-Iglesias, {M A} and T Pelaez and Shields, {R K} and G Garcia-Effron and J Guinea and M Sanguinetti and J Turnidge",

note = "Copyright {\textcopyright} 2016 American Society for Microbiology.",

year = "2017",

month = jan,

doi = "10.1128/aac.01792-16",

language = "English",

volume = "61",

journal = "Antimicrobial Agents and Chemotherapy",

issn = "0066-4804",

publisher = "American Society for Microbiology",

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T1 - Multicenter Study of Method-Dependent Epidemiological Cutoff Values for Detection of Resistance in Candida spp. and Aspergillus spp. to Amphotericin B and Echinocandins for the Etest Agar Diffusion Method

AU - Espinel-Ingroff, A

AU - Arendrup, M

AU - Cantón, E

AU - Cordoba, S

AU - Dannaoui, E

AU - García-Rodríguez, J

AU - Gonzalez, G M

AU - Govender, N P

AU - Martin-Mazuelos, E

AU - Lackner, M

AU - Lass-Flörl, C

AU - Linares Sicilia, M J

AU - Rodriguez-Iglesias, M A

AU - Pelaez, T

AU - Shields, R K

AU - Garcia-Effron, G

AU - Guinea, J

AU - Sanguinetti, M

AU - Turnidge, J

PY - 2017/1

Y1 - 2017/1

N2 - Method-dependent Etest epidemiological cutoff values (ECVs) are not available for susceptibility testing of either Candida or Aspergillus species with amphotericin B or echinocandins. In addition, reference caspofungin MICs for Candida spp. are unreliable. Candida and Aspergillus species wild-type (WT) Etest MIC distributions (microorganisms in a species-drug combination with no detectable phenotypic resistance) were established for 4,341 Candida albicans, 113 C. dubliniensis, 1,683 C. glabrata species complex (SC), 709 C. krusei, 767 C. parapsilosis SC, 796 C. tropicalis, 1,637 Aspergillus fumigatus SC, 238 A. flavus SC, 321 A. niger SC, and 247 A. terreus SC isolates. Etest MICs from 15 laboratories (in Argentina, Europe, Mexico, South Africa, and the United States) were pooled to establish Etest ECVs. Anidulafungin, caspofungin, micafungin, and amphotericin B ECVs (in micrograms per milliliter) encompassing ≥97.5% of the statistically modeled population were 0.016, 0.5, 0.03, and 1 for C. albicans; 0.03, 1, 0.03, and 2 for C. glabrata SC; 0.06, 1, 0.25, and 4 for C. krusei; 8, 4, 2, and 2 for C. parapsilosis SC; and 0.03, 1, 0.12, and 2 for C. tropicalis The amphotericin B ECV was 0.25 μg/ml for C. dubliniensis and 2, 8, 2, and 16 μg/ml for the complexes of A. fumigatus, A. flavus, A. niger, and A. terreus, respectively. While anidulafungin Etest ECVs classified 92% of the Candida fks mutants evaluated as non-WT, the performance was lower for caspofungin (75%) and micafungin (84%) cutoffs. Finally, although anidulafungin (as an echinocandin surrogate susceptibility marker) and amphotericin B ECVs should identify Candida and Aspergillus isolates with reduced susceptibility to these agents using the Etest, these ECVs will not categorize a fungal isolate as susceptible or resistant, as breakpoints do.

AB - Method-dependent Etest epidemiological cutoff values (ECVs) are not available for susceptibility testing of either Candida or Aspergillus species with amphotericin B or echinocandins. In addition, reference caspofungin MICs for Candida spp. are unreliable. Candida and Aspergillus species wild-type (WT) Etest MIC distributions (microorganisms in a species-drug combination with no detectable phenotypic resistance) were established for 4,341 Candida albicans, 113 C. dubliniensis, 1,683 C. glabrata species complex (SC), 709 C. krusei, 767 C. parapsilosis SC, 796 C. tropicalis, 1,637 Aspergillus fumigatus SC, 238 A. flavus SC, 321 A. niger SC, and 247 A. terreus SC isolates. Etest MICs from 15 laboratories (in Argentina, Europe, Mexico, South Africa, and the United States) were pooled to establish Etest ECVs. Anidulafungin, caspofungin, micafungin, and amphotericin B ECVs (in micrograms per milliliter) encompassing ≥97.5% of the statistically modeled population were 0.016, 0.5, 0.03, and 1 for C. albicans; 0.03, 1, 0.03, and 2 for C. glabrata SC; 0.06, 1, 0.25, and 4 for C. krusei; 8, 4, 2, and 2 for C. parapsilosis SC; and 0.03, 1, 0.12, and 2 for C. tropicalis The amphotericin B ECV was 0.25 μg/ml for C. dubliniensis and 2, 8, 2, and 16 μg/ml for the complexes of A. fumigatus, A. flavus, A. niger, and A. terreus, respectively. While anidulafungin Etest ECVs classified 92% of the Candida fks mutants evaluated as non-WT, the performance was lower for caspofungin (75%) and micafungin (84%) cutoffs. Finally, although anidulafungin (as an echinocandin surrogate susceptibility marker) and amphotericin B ECVs should identify Candida and Aspergillus isolates with reduced susceptibility to these agents using the Etest, these ECVs will not categorize a fungal isolate as susceptible or resistant, as breakpoints do.

KW - Amphotericin B/pharmacology

KW - Antifungal Agents/pharmacology

KW - Aspergillus/drug effects

KW - Candida/drug effects

KW - Disk Diffusion Antimicrobial Tests

KW - Drug Resistance, Fungal

KW - Echinocandins/pharmacology

KW - Europe

KW - Latin America

KW - South Africa

KW - United States

U2 - 10.1128/aac.01792-16

DO - 10.1128/aac.01792-16

M3 - Journal article

C2 - 27799206

SN - 0066-4804

VL - 61

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

IS - 1

M1 - e01792-16

ER -