scholarly journals 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

2016 ◽  
Vol 61 (1) ◽  
Author(s):  
A. Espinel-Ingroff ◽  
M. Arendrup ◽  
E. Cantón ◽  
S. Cordoba ◽  
E. Dannaoui ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Susceptibility Testing ◽  
The United States ◽  
Fungal Isolate ◽  
Diffusion Method ◽  
Wild Type ◽  
Candida Spp ◽  
Content Type ◽  
Phenotypic Resistance ◽  
Cutoff Values

ABSTRACTMethod-dependent Etest epidemiological cutoff values (ECVs) are not available for susceptibility testing of eitherCandidaorAspergillusspecies with amphotericin B or echinocandins. In addition, reference caspofungin MICs forCandidaspp. are unreliable.CandidaandAspergillusspecies wild-type (WT) Etest MIC distributions (microorganisms in a species-drug combination with no detectable phenotypic resistance) were established for 4,341Candida albicans, 113C. dubliniensis, 1,683C. glabrataspecies complex (SC), 709C. krusei, 767C. parapsilosisSC, 796C. tropicalis, 1,637Aspergillus fumigatusSC, 238A. flavusSC, 321A. nigerSC, and 247A. terreusSC 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 forC. albicans; 0.03, 1, 0.03, and 2 forC. glabrataSC; 0.06, 1, 0.25, and 4 forC. krusei; 8, 4, 2, and 2 forC. parapsilosisSC; and 0.03, 1, 0.12, and 2 forC. tropicalis. The amphotericin B ECV was 0.25 μg/ml forC. dubliniensisand 2, 8, 2, and 16 μg/ml for the complexes ofA. fumigatus,A. flavus,A. niger, andA. terreus, respectively. While anidulafungin Etest ECVs classified 92% of theCandida fksmutants 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 identifyCandidaandAspergillusisolates with reduced susceptibility to these agents using the Etest, these ECVs will not categorize a fungal isolate as susceptible or resistant, as breakpoints do.

scholarly journals Multicenter Study of Epidemiological Cutoff Values and Detection of Resistance in Candida spp. to Anidulafungin, Caspofungin, and Micafungin Using the Sensititre YeastOne Colorimetric Method

2015 ◽  
Vol 59 (11) ◽  
pp. 6725-6732 ◽  
Author(s):  
A. Espinel-Ingroff ◽  
M. Alvarez-Fernandez ◽  
E. Cantón ◽  
P. L. Carver ◽  
S. C.-A. Chen ◽  
...  
Keyword(s):  
South Africa ◽  
Colorimetric Method ◽  
The United States ◽  
Wild Type ◽  
Candida Spp ◽  
Content Type ◽  
Phenotypic Resistance ◽  
Cutoff Values ◽  
Species Specific ◽  
Broth Dilution

ABSTRACTNeither breakpoints (BPs) nor epidemiological cutoff values (ECVs) have been established forCandidaspp. with anidulafungin, caspofungin, and micafungin when using the Sensititre YeastOne (SYO) broth dilution colorimetric method. In addition, reference caspofungin MICs have so far proven to be unreliable.Candidaspecies wild-type (WT) MIC distributions (for microorganisms in a species/drug combination with no detectable phenotypic resistance) were established for 6,007Candida albicans, 186C. dubliniensis, 3,188C. glabratacomplex, 119C. guilliermondii, 493C. krusei, 205C. lusitaniae, 3,136C. parapsilosiscomplex, and 1,016C. tropicalisisolates. SYO MIC data gathered from 38 laboratories in Australia, Canada, Europe, Mexico, New Zealand, South Africa, and the United States were pooled to statistically define SYO ECVs. ECVs for anidulafungin, caspofungin, and micafungin encompassing ≥97.5% of the statistically modeled population were, respectively, 0.12, 0.25, and 0.06 μg/ml forC. albicans, 0.12, 0.25, and 0.03 μg/ml forC. glabratacomplex, 4, 2, and 4 μg/ml forC. parapsilosiscomplex, 0.5, 0.25, and 0.06 μg/ml forC. tropicalis, 0.25, 1, and 0.25 μg/ml forC. krusei, 0.25, 1, and 0.12 μg/ml forC. lusitaniae, 4, 2, and 2 μg/ml forC. guilliermondii, and 0.25, 0.25, and 0.12 μg/ml forC. dubliniensis. Species-specific SYO ECVs for anidulafungin, caspofungin, and micafungin correctly classified 72 (88.9%), 74 (91.4%), 76 (93.8%), respectively, of 81Candidaisolates with identifiedfksmutations. SYO ECVs may aid in detecting non-WT isolates with reduced susceptibility to anidulafungin, micafungin, and especially caspofungin, since testing the susceptibilities ofCandidaspp. to caspofungin by reference methodologies is not recommended.

scholarly journals Wild-Type MIC Distributions and Epidemiological Cutoff Values for Amphotericin B and Aspergillus spp. for the CLSI Broth Microdilution Method (M38-A2 Document)

2011 ◽  
Vol 55 (11) ◽  
pp. 5150-5154 ◽  
Author(s):  
A. Espinel-Ingroff ◽  
M. Cuenca-Estrella ◽  
A. Fothergill ◽  
J. Fuller ◽  
M. Ghannoum ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Acquired Resistance ◽  
The United States ◽  
Resistance Mechanisms ◽  
Broth Microdilution ◽  
Wild Type ◽  
Content Type ◽  
Microdilution Method ◽  
Cutoff Values ◽  
Broth Microdilution Method

ABSTRACTAlthough clinical breakpoints have not been established for mold testing, epidemiological cutoff values (ECVs) are available forAspergillusspp. versus the triazoles and caspofungin. Wild-type (WT) MIC distributions (organisms in a species-drug combination with no acquired resistance mechanisms) were defined in order to establish ECVs for sixAspergillusspp. and amphotericin B. Two sets (CLSI/EUCAST broth microdilution) of available MICs were evaluated: those forA. fumigatus(3,988/833),A. flavus(793/194),A. nidulans(184/69),A. niger(673/140),A. terreus(545/266), andA. versicolor(135/22). Three sets of data were analyzed: (i) CLSI data gathered in eight independent laboratories in Canada, Europe, and the United States; (ii) EUCAST data from a single laboratory; and (iii) the combined CLSI and EUCAST data. ECVs, expressed in μg/ml, that captured 95%, 97.5%, and 99% of the modeled wild-type population (CLSI and combined data) were as follows: forA. fumigatus, 2, 2, and 4; forA. flavus, 2, 4, and 4; forA. nidulans, 4, 4, and 4; forA. niger, 2, 2, and 2; forA. terreus, 4, 4, and 8; and forA. versicolor, 2, 2, and 2. Similar to the case for the triazoles and caspofungin, amphotericin B ECVs may aid in the detection of strains with acquired mechanisms of resistance to this agent.

scholarly journals Molecular Analysis of Resistance and Detection of Non-Wild-Type Strains Using Etest Epidemiological Cutoff Values for Amphotericin B and Echinocandins for Bloodstream Candida Infections from a Tertiary Hospital in Qatar

2018 ◽  
Vol 62 (9) ◽  
Author(s):  
Saad J. Taj-Aldeen ◽  
Husam Salah ◽  
Winder B. Perez ◽  
Muna Almaslamani ◽  
Mary Motyl ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Hot Spot ◽  
Antifungal Susceptibility ◽  
Tertiary Hospital ◽  
Wild Type ◽  
Content Type ◽  
Cutoff Values ◽  
Echinocandin Resistance ◽  
Candida Infections ◽  
Type Strains

ABSTRACT A total of 301 Candida bloodstream isolates collected from 289 patients over 5 years at a tertiary hospital in Qatar were evaluated. Out of all Candida infections, 53% were diagnosed in patients admitted to the intensive care units. Steady increases in non-albicans Candida species were reported from 2009 to 2014 (30.2% for Candida albicans versus 69.8% for the other Candida species). Etest antifungal susceptibility testing was performed on all recovered clinical isolates to determine echinocandin (micafungin and anidulafungin) and amphotericin B susceptibilities and assess non-wild-type (non-WT) strains (strains for which MICs were above the epidemiological cutoff values). DNA sequence analysis was performed on all isolates to assess the presence of FKS mutations, which confer echinocandin resistance in Candida species. A total of 3.9% of isolates (12/301) among strains of C. albicans and C. orthopsilosis contained FKS hot spot mutations, including heterozygous mutations in FKS1. For C. tropicalis, the Etest appeared to overestimate strains non-WT for micafungin, anidulafungin, and amphotericin B, as 14%, 11%, and 35% of strains, respectively, had values above the epidemiological cutoff value. However, no FKS mutations were identified in this species. For all other species, micafungin best reported the echinocandin non-WT strains relative to the FKS genotype, as anidulafungin tended to overestimate non-wild-type strains. Besides C. tropicalis, few strains were classified as non-WT for amphotericin B.

scholarly journals Comparing Etest and Broth Microdilution for Antifungal Susceptibility Testing of the Most-Relevant Pathogenic Molds

2015 ◽  
Vol 53 (10) ◽  
pp. 3176-3181 ◽  
Author(s):  
Frédéric Lamoth ◽  
Barbara D. Alexander
Keyword(s):  
Amphotericin B ◽  
Antifungal Therapy ◽  
Susceptibility Testing ◽  
Antifungal Susceptibility ◽  
Multidrug Resistant ◽  
Antifungal Susceptibility Testing ◽  
Diffusion Method ◽  
Broth Microdilution ◽  
Content Type ◽  
Broth Microdilution Method

Invasive mold infections are life-threatening diseases for which appropriate antifungal therapy is crucial. Their epidemiology is evolving, with the emergence of triazole-resistantAspergillusspp. and multidrug-resistant non-Aspergillusmolds. Despite the lack of interpretive criteria, antifungal susceptibility testing of molds may be useful in guiding antifungal therapy. The standard broth microdilution method (BMD) is demanding and requires expertise. We assessed the performance of a commercialized gradient diffusion method (Etest method) as an alternative to BMD. The MICs or minimal effective concentrations (MECs) of amphotericin B, voriconazole, posaconazole, caspofungin, and micafungin were assessed for 290 clinical isolates of the most representative pathogenic molds (154Aspergillusand 136 non-Aspergillusisolates) with the BMD and Etest methods. Essential agreements (EAs) within ±2 dilutions of ≥90% between the two methods were considered acceptable. EAs for amphotericin B and voriconazole were >90% for most potentially susceptible species. For posaconazole, the correlation was acceptable forMucoromycotinabut Etest MIC values were consistently lower forAspergillusspp. (EAs of <90%). Excellent EAs were found for echinocandins with highly susceptible (MECs of <0.015 μg/ml) or intrinsically resistant (MECs of >16 μg/ml) strains. However, MEC determinations lacked consistency between methods for strains exhibiting mid-range MECs for echinocandins. We concluded that the Etest method is an appropriate alternative to BMD for antifungal susceptibility testing of molds under specific circumstances, including testing with amphotericin B or triazoles for non-Aspergillusmolds (MucoromycotinaandFusariumspp.). Additional study of molecularly characterized triazole-resistantAspergillusisolates is required to confirm the ability of the Etest method to detect voriconazole and posaconazole resistance amongAspergillusspp.

scholarly journals Wild-Type MIC Distributions and Epidemiological Cutoff Values for Amphotericin B, Flucytosine, and Itraconazole and Candida spp. as Determined by CLSI Broth Microdilution

2012 ◽  
Vol 50 (6) ◽  
pp. 2040-2046 ◽  
Author(s):  
M. A. Pfaller ◽  
A. Espinel-Ingroff ◽  
E. Canton ◽  
M. Castanheira ◽  
M. Cuenca-Estrella ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Broth Microdilution ◽  
Wild Type ◽  
Candida Spp ◽  
Cutoff Values

scholarly journals Multicenter Evaluation of MIC Distributions for Epidemiologic Cutoff Value Definition To Detect Amphotericin B, Posaconazole, and Itraconazole Resistance among the Most Clinically Relevant Species of Mucorales

2015 ◽  
Vol 59 (3) ◽  
pp. 1745-1750 ◽  
Author(s):  
A. Espinel-Ingroff ◽  
A. Chakrabarti ◽  
A. Chowdhary ◽  
S. Cordoba ◽  
E. Dannaoui ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Acquired Resistance ◽  
The United States ◽  
Resistance Mechanisms ◽  
Wild Type ◽  
Content Type ◽  
Syncephalastrum Racemosum ◽  
Mucor Indicus ◽  
Clinical Breakpoints ◽  
Lichtheimia Corymbifera

ABSTRACTClinical breakpoints (CBPs) have not been established for theMucoralesand any antifungal agent. In lieu of CBPs, epidemiologic cutoff values (ECVs) are proposed for amphotericin B, posaconazole, and itraconazole and fourMucoralesspecies. Wild-type (WT) MIC distributions (organisms in a species-drug combination with no detectable acquired resistance mechanisms) were defined with available pooled CLSI MICs from 14 laboratories (Argentina, Australia, Canada, Europe, India, Mexico, and the United States) as follows: 10Apophysomyces variabilis, 32Cunninghamella bertholletiae, 136Lichtheimia corymbifera, 10Mucor indicus, 123M. circinelloides, 19M. ramosissimus, 349Rhizopus arrhizus, 146R. microsporus, 33Rhizomucor pusillus, and 36Syncephalastrum racemosumisolates. CLSI broth microdilution MICs were aggregated for the analyses. ECVs comprising ≥95% and ≥97.5% of the modeled populations were as follows: amphotericin B ECVs forL. corymbiferawere 1 and 2 μg/ml, those forM. circinelloideswere 1 and 2 μg/ml, those forR. arrhizuswere 2 and 4 μg/ml, and those forR. microsporuswere 2 and 2 μg/ml, respectively; posaconazole ECVs forL. corymbiferawere 1 and 2, those forM. circinelloideswere 4 and 4, those forR. arrhizuswere 1 and 2, and those forR. microsporuswere 1 and 2, respectively; both itraconazole ECVs forR. arrhizuswere 2 μg/ml. ECVs may aid in detecting emerging resistance or isolates with reduced susceptibility (non-WT MICs) to the agents evaluated.

scholarly journals In VitroActivity of ASP2397 against Aspergillus Isolates with or without Acquired Azole Resistance Mechanisms

2015 ◽  
Vol 60 (1) ◽  
pp. 532-536 ◽  
Author(s):  
Maiken Cavling Arendrup ◽  
Rasmus Hare Jensen ◽  
Manuel Cuenca-Estrella
Keyword(s):  
Amphotericin B ◽  
Target Gene ◽  
Antifungal Agents ◽  
Susceptibility Testing ◽  
Resistance Mechanisms ◽  
Azole Resistance ◽  
Wild Type ◽  
Resistance Mutations ◽  
Content Type

ABSTRACTASP2397 is a new compound with a novel and as-yet-unknown target different from that of licensed antifungal agents. It has activity againstAspergillusandCandida glabrata. We compared itsin vitroactivity against wild-type and azole-resistantA. fumigatusandA. terreusisolates with that of amphotericin B, itraconazole, posaconazole, and voriconazole. Thirty-four isolates, including 4 wild-typeA. fumigatusisolates, 24A. fumigatusisolates with alterations in CYP51A TR/L98H (5 isolates), M220 (9 isolates), G54 (9 isolates), and HapE (1 isolate), andA. terreusisolates (2 wild-type isolates and 1 isolate with an M217I CYP51A alteration), were analyzed. EUCAST E.Def 9.2 and CLSI M38-A2 MIC susceptibility testing was performed. ASP2397 MIC50values (in milligrams per liter, with MIC ranges in parentheses) determined by EUCAST and CLSI were 0.5 (0.25 to 1) and 0.25 (0.06 to 0.25) againstA. fumigatusCYP51A wild-type isolates and were similarly 0.5 (0.125 to >4) and 0.125 (0.06 to >4) against azole-resistantA. fumigatusisolates, respectively. These values were comparable to those for amphotericin B, which were 0.25 (0.125 to 0.5) and 0.25 (0.125 to 0.25) against wild-type isolates and 0.25 (0.125 to 1) and 0.25 (0.125 to 1) against isolates with azole resistance mechanisms, respectively. In contrast, MICs for the azole compounds were elevated and highest for itraconazole: >4 (1 to >4) and 4 (0.5 to >4) against isolates with azole resistance mechanisms compared to 0.125 (0.125 to 0.25) and 0.125 (0.06 to 0.25) against wild-type isolates, respectively. ASP2397 was active againstA. terreusCYP51A wild-type isolates (MIC 0.5 to 1), whereas MICs of both azole and ASP2397 were elevated for the mutant isolate. ASP2397 displayedin vitroactivity againstA. fumigatusandA. terreusisolates which was independent of the presence or absence of azole target gene resistance mutations inA. fumigatus. The findings are promising at a time when azole-resistantA. fumigatusis emerging globally.

scholarly journals Multicenter Study of Anidulafungin and Micafungin MIC Distributions and Epidemiological Cutoff Values for Eight Candida Species and the CLSI M27-A3 Broth Microdilution Method

2013 ◽  
Vol 58 (2) ◽  
pp. 916-922 ◽  
Author(s):  
M. A. Pfaller ◽  
A. Espinel-Ingroff ◽  
B. Bustamante ◽  
E. Canton ◽  
D. J. Diekema ◽  
...  
Keyword(s):  
Acquired Resistance ◽  
The United States ◽  
Resistance Mechanisms ◽  
Broth Microdilution ◽  
Wild Type ◽  
Content Type ◽  
Microdilution Method ◽  
Cutoff Values ◽  
Broth Microdilution Method ◽  
Species Specific

ABSTRACTSince epidemiological cutoff values (ECVs) using CLSI MICs from multiple laboratories are not available forCandidaspp. and the echinocandins, we established ECVs for anidulafungin and micafungin on the basis of wild-type (WT) MIC distributions (for organisms in a species-drug combination with no detectable acquired resistance mechanisms) for 8,210Candida albicans, 3,102C. glabrata, 3,976C. parapsilosis, 2,042C. tropicalis, 617C. krusei, 258C. lusitaniae, 234C. guilliermondii, and 131C. dubliniensisisolates. CLSI broth microdilution MIC data gathered from 15 different laboratories in Canada, Europe, Mexico, Peru, and the United States were aggregated to statistically define ECVs. ECVs encompassing 97.5% of the statistically modeled population for anidulafungin and micafungin were, respectively, 0.12 and 0.03 μg/ml forC. albicans, 0.12 and 0.03 μg/ml forC. glabrata, 8 and 4 μg/ml forC. parapsilosis, 0.12 and 0.06 μg/ml forC. tropicalis, 0.25 and 0.25 μg/ml forC. krusei, 1 and 0.5 μg/ml forC. lusitaniae, 8 and 2 μg/ml forC. guilliermondii, and 0.12 and 0.12 μg/ml forC. dubliniensis. Previously reported single and multicenter ECVs defined in the present study were quite similar or within 1 2-fold dilution of each other. For a collection of 230 WT isolates (nofksmutations) and 51 isolates withfksmutations, the species-specific ECVs for anidulafungin and micafungin correctly classified 47 (92.2%) and 51 (100%) of thefksmutants, respectively, as non-WT strains. These ECVs may aid in detecting non-WT isolates with reduced susceptibility to anidulafungin and micafungin due tofksmutations.

scholarly journals Multilaboratory Study of Epidemiological Cutoff Values for Detection of Resistance in Eight Candida Species to Fluconazole, Posaconazole, and Voriconazole

2014 ◽  
Vol 58 (4) ◽  
pp. 2006-2012 ◽  
Author(s):  
A. Espinel-Ingroff ◽  
M. A. Pfaller ◽  
B. Bustamante ◽  
E. Canton ◽  
A. Fothergill ◽  
...  
Keyword(s):  
United States ◽  
Candida Species ◽  
The United States ◽  
Broth Microdilution ◽  
Wild Type ◽  
Content Type ◽  
Cutoff Values ◽  
Prevalent Species ◽  
Single Laboratory

ABSTRACTAlthough epidemiological cutoff values (ECVs) have been established forCandidaspp. and the triazoles, they are based on MIC data from a single laboratory. We have established ECVs for eightCandidaspecies and fluconazole, posaconazole, and voriconazole based on wild-type (WT) MIC distributions for isolates ofC. albicans(n= 11,241 isolates),C. glabrata(7,538),C. parapsilosis(6,023),C. tropicalis(3,748),C. krusei(1,073),C. lusitaniae(574),C. guilliermondii(373), andC. dubliniensis(162). The 24-h CLSI broth microdilution MICs were collated from multiple laboratories (in Canada, Brazil, Europe, Mexico, Peru, and the United States). The ECVs for distributions originating from ≥6 laboratories, which included ≥95% of the modeled WT population, for fluconazole, posaconazole, and voriconazole were, respectively, 0.5, 0.06 and 0.03 μg/ml forC. albicans, 0.5, 0.25, and 0.03 μg/ml forC. dubliniensis, 8, 1, and 0.25 μg/ml forC. glabrata, 8, 0.5, and 0.12 μg/ml forC. guilliermondii, 32, 0.5, and 0.25 μg/ml forC. krusei, 1, 0.06, and 0.06 μg/ml forC. lusitaniae, 1, 0.25, and 0.03 μg/ml forC. parapsilosis, and 1, 0.12, and 0.06 μg/ml forC. tropicalis. The low number of MICs (<100) for other less prevalent species (C. famata,C. kefyr,C. orthopsilosis,C. rugosa) precluded ECV definition, but their MIC distributions are documented. Evaluation of our ECVs for some species/agent combinations using published individual MICs for 136 isolates (harboring mutations in or upregulation ofERG11,MDR1,CDR1, orCDR2) and 64 WT isolates indicated that our ECVs may be useful in distinguishing WT from non-WT isolates.

scholarly journals Cryptococcus neoformans-Cryptococcus gattii Species Complex: an International Study of Wild-Type Susceptibility Endpoint Distributions and Epidemiological Cutoff Values for Amphotericin B and Flucytosine

2012 ◽  
Vol 56 (6) ◽  
pp. 3107-3113 ◽  
Author(s):  
A. Espinel-Ingroff ◽  
A. Chowdhary ◽  
M. Cuenca-Estrella ◽  
A. Fothergill ◽  
J. Fuller ◽  
...  
Keyword(s):  
Cryptococcus Neoformans ◽  
Amphotericin B ◽  
Species Complex ◽  
Acquired Resistance ◽  
International Study ◽  
Resistance Mechanisms ◽  
Cryptococcus Gattii ◽  
Wild Type ◽  
Content Type ◽  
Cutoff Values

ABSTRACTClinical breakpoints (CBPs) are not available for theCryptococcus neoformans-Cryptococcus gattiispecies complex. MIC distributions were constructed for the wild type (WT) to establish epidemiologic cutoff values (ECVs) forC. neoformansandC. gattiiversus amphotericin B and flucytosine. A total of 3,590 amphotericin B and 3,045 flucytosine CLSI MICs forC. neoformans(including 1,002 VNI isolates and 8 to 39 VNII, VNIII, and VNIV isolates) and 985 and 853 MICs forC. gattii, respectively (including 42 to 259 VGI, VGII, VGIII, and VGIV isolates), were gathered in 9 to 16 (amphotericin B) and 8 to 13 (flucytosine) laboratories (Europe, United States, Australia, Brazil, Canada, India, and South Africa) and aggregated for the analyses. Additionally, 442 amphotericin B and 313 flucytosine MICs measured by using CLSI-YNB medium instead of CLSI-RPMI medium and 237 Etest amphotericin B MICs forC. neoformanswere evaluated. CLSI-RPMI ECVs for distributions originating in ≥3 laboratories (with the percentages of isolates for which MICs were less than or equal to ECVs given in parentheses) were as follows: for amphotericin B, 0.5 μg/ml forC. neoformansVNI (97.2%) andC. gattiiVGI and VGIIa (99.2 and 97.5%, respectively) and 1 μg/ml forC. neoformans(98.5%) andC. gattiinontyped (100%) and VGII (99.2%) isolates; for flucytosine, 4 μg/ml forC. gattiinontyped (96.4%) and VGI (95.7%) isolates, 8 μg/ml for VNI (96.6%) isolates, and 16 μg/ml forC. neoformansnontyped (98.6%) andC. gattiiVGII (97.1%) isolates. Other molecular types had apparent variations in MIC distributions, but the number of laboratories contributing data was too low to allow us to ascertain that the differences were due to factors other than assay variation. ECVs may aid in the detection of isolates with acquired resistance mechanisms.

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