[Show abstract][Hide abstract] ABSTRACT: ECVs (epidemiological cutoff values) are not available for Cryptococcus spp. and isavuconazole. Isavuconazole ECVs based on wild type MIC distributions for 438 Cryptococcus neoformans nongenotyped, 870 genotype VNI and 406 C. gattii from six laboratories and different geographical areas were: 0.06, 0.12 and 0.25 μg/ml, respectively. These ECVs may aid in detecting isavuconazole non-WT isolates with reduced susceptibility to this agent.
Antimicrobial Agents and Chemotherapy 10/2014; · 4.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although ECVs (epidemiologic cutoff values) have been established for Candida spp. and the triazoles, they are based on MIC data from a single laboratory. We have established ECVs for eight Candida species and fluconazole, posaconazole and voriconazole based on wild-type (WT) MIC distributions for isolates of C. albicans (11, 241), C. glabrata (7, 538), C. parapsilosis (6, 023), C. tropicalis (3, 748), C. krusei (1, 073), C. lusitaniae (574), C. guilliermondii (373), and C. dubliniensis (162). The 24-h CLSI broth microdilution MICs were collated from multiple laboratories (Canada, Brazil, Europe, Mexico, Peru, and the United States). ECVs for distributions originating from ≥6 laboratories, which included ≥95% of the modelled WT population (fluconazole, posaconazole, and voriconazole, respectively) were: 0.5, 0.06 and 0.03 μg/ml for C. albicans; 0.5, 0.25, and 0.03 μg/ml for C. dubliniensis; 8, 1 and 0.25 μg/ml for C. glabrata; 8, 0.5 and 0.12 μg/ml for C. guilliermondii; 32, 0.5 and 0.25 μg/ml for C. krusei; 1, 0.06 and 0.06 μg/ml for C. lusitaniae; 1, 0.25 and 0.03 μg/ml for C. parapsilosis; and 1, 0.12 and 0.06 μg/ml for C. 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 (harbouring mutations in or up-regulation of ERG11, MDR1, CDR1 and CDR2) and 64 WT isolates indicated that our ECVs may be useful in distinguishing WT from non-WT isolates.
Antimicrobial Agents and Chemotherapy 01/2014; · 4.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Since epidemiological cutoff values (ECVs) using CLSI MICs from multiple laboratories are not available for Candida spp. and the echinocandins, we established ECVs for anidulafungin and micafungin based on wild-type (WT) MIC distributions (organisms in a species-drug combination with no detectable acquired resistance mechanisms) for 8,210 Candida albicans, 3,102 C. glabrata, 3,976 C. parapsilosis, 2,042 C. tropicalis, 617 C. krusei, 258 C. lusitaniae, 234 C. guilliermondii, and 131 C. dubliniensis isolates. 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 (anidulafungin and micafungin, respectively) were 0.12 and 0.03 μg/mL for C. albicans, 0.12 and 0.03 μg/mL for C. glabrata, 8 and 4 μg/mL for C. parapsilosis, 0.12 and 0.06 μg/mL for C. tropicalis, 0.25 and 0.25 μg/mL for C. krusei, 1 and 0.5 μg/mL for C. lusitaniae, 8 and 2 μg/mL for C. guilliermondii, and 0.12 and 0.12 μg/mL for C. dubliniensis. Previously reported single and the multicenter ECVs defined in the present study were quite similar or within 1 two-fold dilution from each other. For a collection of 230 WT (no fks mutations) and 51 isolates with fks mutations, the species-specific ECVs for anidulafungin and micafungin correctly classified 47 (92.2%) and 51 (100%) of the fks mutants, respectively, as non-WT strains. These ECVs may aid in detecting non-WT isolates with reduced susceptibility to anidulafungin and micafungin due to fks mutations.
Antimicrobial Agents and Chemotherapy 11/2013; · 4.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although CLSI clinical breakpoints (CBPs) are available for interpreting echinocandin MICs for Candida spp., epidemiologic cutoff values (ECVs) based on collective MIC data from multiple laboratories have not been defined. While collating CLSI caspofungin MICs for 145 to 11,550 Candida isolates from 17 laboratories (Brazil, Canada, Europe, Mexico, Peru and the United States), we observed an extraordinary amount of modal variability (wide ranges) among laboratories as well as truncated and bimodal MIC distributions. The species-specific modes across different laboratories ranged from: 0.016-0.5 μg/ml for C. albicans and C. tropicalis; 0.031-0.5 μg/ml for C. glabrata; 0.063-1 μg/ml for C. krusei; variability was also similar among C. dubliniensis and C. lusitaniae. The exceptions were C. parapsilosis and C. guilliermondii MIC distributions, where most modes were within one twofold dilution of each other. These findings were consistent with available EUCAST data (403 to 2,556 MICs) for C. albicans, C. glabrata, C. krusei, and C. tropicalis. Although many factors (caspofungin powder source, stock solution solvent, powder storage time length and temperature, and MIC determination testing parameters) were examined as a potential cause of such unprecedented variability, a single specific cause was not identified. Therefore, it seems highly likely that the use of the CLSI species-specific caspofungin CBPs could lead to reporting an excessive number of wild-type [WT] (e.g., C. glabrata and C. krusei) as either non-WT or resistant isolates. Until this problem is resolved, routine testing or reporting of CLSI caspofungin MICs for Candida is not recommended; micafungin or anidulafungin data could be used instead.
Antimicrobial Agents and Chemotherapy 09/2013; · 4.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Epidemiologic cutoff values (ECVs) were established for the new triazole isavuconazole and Aspergillus spp. Wild type (WT) MIC distributions (organisms in a species/drug combination with no detectable acquired resistance mechanisms) were defined with the available isolates of the following Aspergillus species complexes: 855 A. fumigatus, 444 A. flavus, 106 A. nidulans, 207 A. niger, 384 A. terreus, and 75 A. versicolor; 29 Aspergillus section Usti isolates were also included. CLSI broth microdilution MIC data gathered in Europe, India, Mexico and the United States were aggregated to statistically define ECVs. ECVs expressed in μg/ml were: A. fumigatus species complex 1; A. flavus species complex 1; A. nidulans species complex 0.25; A. niger species complex 4, A. terreus species complex 1 and A. versicolor species complex 1; due to the low number of isolates, an ECV was not proposed for Aspergillus section Usti. These ECVs may aid in detecting isavuconazole non-WT isolates with reduced susceptibility to this agent due to cyp51A (an A. fumigatus species complex resistance mechanism among the triazoles) or other mutations.
Antimicrobial Agents and Chemotherapy 05/2013; · 4.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The U.S. Clinical and Laboratory Standards Institute (CLSI) and the European Committee of Antimicrobial Susceptibility Testing (AFST-EUCAST) have developed broth microdilution methodologies for testing yeasts and filamentous fungi (molds). The mission of these methodologies is to identify in vitro antifungal resistance, which is accomplished by the use of either clinical breakpoints (CBPs), or to a lesser degree, epidemiologic cutoff values (ECVs). The newly adjusted and species-specific CLSI CBPs for Candida spp. versus fluconazole and voriconazole have ameliorated some of the differences between the two methodologies. In the absence of CBPs for mold testing, CLSI ECVs are available for six Aspergillus species versus the triazoles, caspofungin and amphotericin B. Recently, breakpoints were developed by the EUCAST for certain Aspergillus spp. versus amphotercin B, itraconazole and posaconazole, which to some extent are comparable to ECVs. We summarize these latest accomplishments, which have made possible the harmonization of some susceptibility cutoffs, if not methodologies for some agent/species combinations.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES: Candida lusitaniae fungaemia, although infrequent (1%), is more common in immunocompromised patients than Candida albicans. Although infections produced by Candida spp. are therapeutic targets for treatment with echinocandins, little information is available regarding their killing kinetics against C. lusitaniae. The objectives of this study were to determine the killing kinetics of anidulafungin, micafungin and caspofungin against four blood isolates of C. lusitaniae by time-kill methodology. METHODS: Time-kill studies were performed in RMPI 1640 medium (5 mL, inoculum ∼10(5) cfu/mL). The number of cfu/mL was determined at 0, 2, 4, 6 and 24 h. The anidulafungin concentrations assayed were 0.03, 0.12, 0.5, 2 and 8 mg/L, while micafungin and caspofungin concentrations were 0.25, 1, 4, 16 and 32 mg/L. RESULTS: MIC ranges were 0.03-1 mg/L (anidulafungin), 0.016-0.06 mg/L (micafungin) and 0.03-1 mg/L (caspofungin). The mean maximum log decrease in cfu/mL was reached with 2 mg/L anidulafungin (1.85 ± 0.4 log), 32 mg/L caspofungin (5.5 ± 0.2 log) and 32 mg/L micafungin (2.65 ± 1.9 log). Only caspofungin and micafungin reached the fungicidal endpoint (99.9% growth reduction or a 3 log decrease) with 32 mg/L at 22.8 h (caspofungin) and 26.5 h (micafungin). Analysis of variance showed significant differences in killing activity among isolates, but not among concentrations reached in serum or echinocandins. CONCLUSIONS: Anidulafungin and micafungin exhibit greater killing rates than caspofungin. Caspofungin was the only echinocandin that reached the fungicidal endpoint before 24 h, but at drug concentrations (≥16 mg/L) not usually reached in serum. The echinocandin killing rate was isolate dependent and concentration independent.
Journal of Antimicrobial Chemotherapy 12/2012; · 5.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Epidemiological cutoff values (ECVs) for the Cryptococcus neoformans-Cryptococcus gattii species complex versus fluconazole, itraconazole, posaconazole, and voriconazole are not available. We established ECVs for these species and agents based on wild-type (WT) MIC distributions. A total of 2,985 to 5,733 CLSI MICs for C. neoformans (including isolates of molecular type VNI [MICs for 759 to 1,137 isolates] and VNII, VNIII, and VNIV [MICs for 24 to 57 isolates]) and 705 to 975 MICs for C. gattii (including 42 to 260 for VGI, VGII, VGIII, and VGIV isolates) were gathered in 15 to 24 laboratories (Europe, United States, Argentina, Australia, Brazil, Canada, Cuba, India, Mexico, and South Africa) and were aggregated for analysis. Additionally, 220 to 359 MICs measured using CLSI yeast nitrogen base (YNB) medium instead of CLSI RPMI medium for C. neoformans were evaluated. CLSI RPMI medium ECVs for distributions originating from at least three laboratories, which included ≥95% of the modeled WT population, were as follows: fluconazole, 8 μg/ml (VNI, C. gattii nontyped, VGI, VGIIa, and VGIII), 16 μg/ml (C. neoformans nontyped, VNIII, and VGIV), and 32 μg/ml (VGII); itraconazole, 0.25 μg/ml (VNI), 0.5 μg/ml (C. neoformans and C. gattii nontyped and VGI to VGIII), and 1 μg/ml (VGIV); posaconazole, 0.25 μg/ml (C. neoformans nontyped and VNI) and 0.5 μg/ml (C. gattii nontyped and VGI); and voriconazole, 0.12 μg/ml (VNIV), 0.25 μg/ml (C. neoformans and C. gattii nontyped, VNI, VNIII, VGII, and VGIIa,), and 0.5 μg/ml (VGI). The number of laboratories contributing data for other molecular types was too low to ascertain that the differences were due to factors other than assay variation. In the absence of clinical breakpoints, our ECVs may aid in the detection of isolates with acquired resistance mechanisms and should be listed in the revised CLSI M27-A3 and CLSI M27-S3 documents.
Antimicrobial Agents and Chemotherapy 09/2012; 56(11):5898-906. · 4.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We tested the susceptibility of caspofungin, micafungin, and anidulafungin against Aspergillus spp. isolates by the new Clinical and Laboratory Standards Institute M51-A disk diffusion (DD) and the broth microdilution methods. A total of 65 clinical isolates of Aspergillus spp. were evaluated. The DD assay was performed on nonsupplemented Müeller-Hinton agar using caspofungin 2-μg, micafungin 1-μg, and anidulafungin 2-μg disks. Echinocandin minimal effective concentrations (MECs) and inhibition zones (IZs) were read after 24 to 48 (A. terreus) h at 35 °C. Caspofungin MECs for all Aspergillus spp. strains tested were ≤ 0.25 μg/mL; IZs were ≥ 15 mm for most species except for A. terreus (11-22 mm). Both micafungin and anidulafungin MECs were ≤ 0.015 μg/mL, but micafungin IZs were ≥ 14 mm while anidulafungin IZs were ≥ 22 mm. As for caspofungin, the DD method could be a useful method for susceptibility testing of micafungin and anidulafungin against Aspergillus spp.
[Show abstract][Hide abstract] ABSTRACT: Clinical breakpoints (CBPs) and epidemiological cutoff values (ECVs) have been established for several Candida spp. and the newer triazoles and echinocandins but are not yet available for older antifungal agents, such as amphotericin B, flucytosine, or itraconazole. We determined species-specific ECVs for amphotericin B (AMB), flucytosine (FC) and itraconazole (ITR) for eight Candida spp. (30,221 strains) using isolates from 16 different laboratories in Brazil, Canada, Europe, and the United States, all tested by the CLSI reference microdilution method. The calculated 24- and 48-h ECVs expressed in μg/ml (and the percentages of isolates that had MICs less than or equal to the ECV) for AMB, FC, and ITR, respectively, were 2 (99.8)/2 (99.2), 0.5 (94.2)/1 (91.4), and 0.12 (95.0)/0.12 (92.9) for C. albicans; 2 (99.6)/2 (98.7), 0.5 (98.0)/0.5 (97.5), and 2 (95.2)/4 (93.5) for C. glabrata; 2 (99.7)/2 (97.3), 0.5 (98.7)/0.5 (97.8), and 05. (99.7)/0.5 (98.5) for C. parapsilosis; 2 (99.8)/2 (99.2), 0.5 (93.0)/1 (90.5), and 0.5 (97.8)/0.5 (93.9) for C. tropicalis; 2 (99.3)/4 (100.0), 32 (99.4)/32 (99.3), and 1 (99.0)/2 (100.0) for C. krusei; 2 (100.0)/4 (100.0), 0.5 (95.3)/1 (92.9), and 0.5 (95.8)/0.5 (98.1) for C. lusitaniae; -/2 (100.0), 0.5 (98.8)/0.5 (97.7), and 0.25 (97.6)/0.25 (96.9) for C. dubliniensis; and 2 (100.0)/2 (100.0), 1 (92.7)/-, and 1 (100.0)/2 (100.0) for C. guilliermondii. In the absence of species-specific CBP values, these wild-type (WT) MIC distributions and ECVs will be useful for monitoring the emergence of reduced susceptibility to these well-established antifungal agents.
Journal of clinical microbiology 03/2012; 50(6):2040-6. · 4.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Clinical breakpoints (CBPs) are not available for the Cryptococcus neoformans-Cryptococcus gattii species complex. MIC distributions were constructed for the wild type (WT) to establish epidemiologic cutoff values (ECVs) for C. neoformans and C. gattii versus amphotericin B and flucytosine. A total of 3,590 amphotericin B and 3,045 flucytosine CLSI MICs for C. neoformans (including 1,002 VNI isolates and 8 to 39 VNII, VNIII, and VNIV isolates) and 985 and 853 MICs for C. 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 for C. neoformans were 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 for C. neoformans VNI (97.2%) and C. gattii VGI and VGIIa (99.2 and 97.5%, respectively) and 1 μg/ml for C. neoformans (98.5%) and C. gattii nontyped (100%) and VGII (99.2%) isolates; for flucytosine, 4 μg/ml for C. gattii nontyped (96.4%) and VGI (95.7%) isolates, 8 μg/ml for VNI (96.6%) isolates, and 16 μg/ml for C. neoformans nontyped (98.6%) and C. gattii VGII (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.
Antimicrobial Agents and Chemotherapy 03/2012; 56(6):3107-13. · 4.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Methods developed for testing filamentous fungi (molds) include standardized broth microdilution (Clinical and Laboratory Standards Institute [CLSI] and European Committee for Antimicrobial Susceptibility Testing [AFST- EUCAST]) methods and disk diffusion (CLSI) methods. Quality control limits also are available from CLSI for MIC (minimal inhibitory concentration), MEC (minimal effective concentration), and zone diameters. Although clinical break- points based on correlations of in vitro results with clinical outcome have not been established, epidemiologic cutoff val- ues have been defined for six Aspergillus species and the triazoles, caspofungin, and amphotericin B. The link between resistance molecular mechanisms, elevated MICs, and clinical treatment failure has also been documented, especially for Aspergillus and the triazoles. Other insights into the potential clinical value of high MICs have also been reported. Various commercial methods (e.g., YeastOne, Etest, and Neo- Sensitabs) have been evaluated in comparison with reference methods. This review summarizes and discusses these developments.
Current Fungal Infection Reports 03/2012; 6(1):1-10.
[Show abstract][Hide abstract] ABSTRACT: Although clinical breakpoints have not been established for mold testing, epidemiological cutoff values (ECVs) are available for Aspergillus spp. 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 six Aspergillus spp. and amphotericin B. Two sets (CLSI/EUCAST broth microdilution) of available MICs were evaluated: those for A. fumigatus (3,988/833), A. flavus (793/194), A. nidulans (184/69), A. niger (673/140), A. terreus (545/266), and A. 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: for A. fumigatus, 2, 2, and 4; for A. flavus, 2, 4, and 4; for A. nidulans, 4, 4, and 4; for A. niger, 2, 2, and 2; for A. terreus, 4, 4, and 8; and for A. 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.
Antimicrobial Agents and Chemotherapy 08/2011; 55(11):5150-4. · 4.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We reassessed the Clinical and Laboratory Standards Institute (CLSI) clinical breakpoints (CBPs) for voriconazole. We examined i) the essential (EA: ±2 dilutions) and categorical agreement between 24-h CLSI and EUCAST methods for voriconazole testing of Candida, ii) wild-type (WT) MICs and epidemiologic cutoff values (ECVs) for voriconazole by both CLSI and EUCAST methods, and iii) correlation of MICs with outcomes from previously published data using CLSI methods. We applied these findings to propose new 24-h species-specific CLSI CBPs. Adjusted 24-h CBPs for voriconazole and C. albicans, C. tropicalis, and C. parapsilosis (susceptible, ≤ 0.125 μg/mL; intermediate, 0.25-0.5 μg/mL; resistant, ≥ 1 μg/mL) should be more sensitive for detecting emerging resistance among common Candida species and provide consistency with EUCAST CBPs. In the absence of CBPs for voriconazole and C. glabrata (and less common species), we recommend that their respective ECVs be used to detect the emergence of non-WT strains.
[Show abstract][Hide abstract] ABSTRACT: Although Clinical and Laboratory Standards Institute (CLSI) disk diffusion assay standard conditions are available for susceptibility testing of filamentous fungi (molds) to antifungal agents, quality control (QC) disk diffusion zone diameter ranges have not been established. This multicenter study documented the reproducibility of tests for one isolate each of five molds (Paecilomyces variotii ATCC MYA-3630, Aspergillus fumigatus ATCC MYA-3626, A. flavus ATCC MYA-3631, A. terreus ATCC MYA-3633, and Fusarium verticillioides [moniliforme] ATCC MYA-3629) and Candida krusei ATCC 6258 by the CLSI disk diffusion method (M51-A document). The zone diameter ranges for selected QC isolates were as follows: P. variotii ATCC MYA-3630, amphotericin B (15 to 24 mm), itraconazole (20 to 31 mm), and posaconazole (33 to 43 mm); A. fumigatus ATCC MYA-3626, amphotericin B (18 to 25 mm), itraconazole (11 to 21 mm), posaconazole (28 to 35 mm), and voriconazole (25 to 33 mm); and C. krusei, amphotericin B (18 to 27 mm), itraconazole (18 to 26 mm), posaconazole (28 to 38 mm), and voriconazole (29 to 39 mm). Due to low testing reproducibility, zone diameter ranges were not proposed for the other three molds.
Journal of clinical microbiology 05/2011; 49(7):2568-71. · 4.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Micafungin Etest and Clinical and Laboratory Standards Institute (CLSI) MICs were compared for 337 Candida spp. isolates. The performance of Etest for testing the susceptibilities of Candida spp. to micafungin was evaluated by the assessment of both categorical (CA) and essential (EA) agreements. The CA was evaluated 2 ways: (i) by the ability of Etest to separate resistant (nontreatable) from susceptible (treatable) isolates by using the newly adjusted species-specific micafungin clinical breakpoints (CBPs) that are available for most of the common species tested and (ii) by the ability to separate wild type (WT) from non-WT isolates or those harboring FKS mutations (with reduced echinocandin susceptibility) by using micafungin epidemiologic cutoff values (ECVs). Etest and CLSI MICs were in EA when the MICs were within 2 log(2) dilutions. Based on agreement percentages, our data indicated that Etest is suitable to test micafungin for most of the Candida species evaluated (overall EA 94.7%; overall CA according to CBPs 97.2% and according to ECVs 97.3%). However, the number of resistant isolates was small, so further evaluations are needed with a higher number of such isolates including more resistant or those with known mechanisms of resistance (non-WT).
[Show abstract][Hide abstract] ABSTRACT: The antifungal broth microdilution (BMD) method of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) was compared with CLSI BMD method M27-A3 for fluconazole, posaconazole, and voriconazole susceptibility testing of 1,056 isolates of Candida. The isolates were obtained in 2009 from more than 60 centers worldwide and included 560 isolates of C. albicans, 175 of C. glabrata, 162 of C. parapsilosis, 124 of C. tropicalis, and 35 of C. krusei. The overall essential agreement (EA) between EUCAST and CLSI results ranged from 96.9% (voriconazole) to 98.6% (fluconazole). The categorical agreement (CA) between methods and species of Candida was assessed using previously determined epidemiological cutoff values (ECVs). The ECVs (expressed as μg/ml) for fluconazole, posaconazole, and voriconazole, respectively, were as follows: 0.12, 0.06, and 0.03 for C. albicans; 32, 2, and 0.5 for C. glabrata; 2, 0.25, and 0.12 for C. parapsilosis; 2, 0.12, and 0.06 for C. tropicalis; 64, 0.5, and 0.5 for C. krusei. Excellent CA was observed for all comparisons between the EUCAST and CLSI results for fluconazole, posaconazole, and voriconazole, respectively, for each species: 98.9%, 93.6%, and 98.6% for C. albicans; 96.0%, 98.9%, and 93.7% for C. glabrata; 90.8%, 98.1%, and 98.1% for C. parapsilosis; 99.2%, 99.2%, and 96.8% for C. tropicalis; 97.1%, 97.1%, and 97.1% for C. krusei. We demonstrate high levels of EA and CA between the CLSI and EUCAST BMD methods for testing of triazoles against Candida when the MICs were determined after 24 h and ECVs were used to differentiate wild-type (WT) from non-WT strains. These results provide additional data in favor of the harmonization of these two methods.
Journal of clinical microbiology 03/2011; 49(3):845-50. · 4.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The echinocandins anidulafungin, caspofungin, and micafungin have a broad and similar spectrum of in vitro and in vivo activity against most Candida spp. Minimal inhibitory concentrations (MICs) for Candida spp. are usually below 1 μg/mL for most isolates. The exceptions are Candidaparapsilosis and C. guilliermondii. Species-specific clinical breakpoints (CBPs) and epidemiologic cutoff values (ECVs) have been proposed by the Clinical and Laboratory Standards Institute (CLSI) for the eight most common Candida spp. versus each echinocandin; these values are useful to detect in vitro antifungal resistance (CBPs) and to identify isolates harboring fks mutations or having reduced susceptibility (ECVs). This paper presents a review of the literature (2006-2010) regarding the in vitro activity similarities or differences among the three echinocandins against Candida spp.; different parameters or measurements of in vitro potency were evaluated. The focus of the review is the non-Candida albicans species.
[Show abstract][Hide abstract] ABSTRACT: Clinical breakpoints have not been established for mold testing. Epidemiologic cutoff values (ECVs) are available for six Aspergillus spp. and the triazoles, but not for caspofungin. Wild-type (WT) minimal effective concentration (MEC) distributions (organisms in a species-drug combination with no acquired resistance mechanisms) were defined in order to establish ECVs for six Aspergillus spp. and caspofungin. The number of available isolates was as follows: 1,691 A. fumigatus, 432 A. flavus, 192 A. nidulans, 440 A. niger, 385 A. terreus, and 75 A. versicolor isolates. CLSI broth microdilution MEC data gathered in five independent laboratories in Canada, Europe, and the United States were aggregated for the analyses. ECVs expressed in μg/ml that captured 95% and 99% of the modeled wild-type population were for A. fumigatus 0.5 and 1, A. flavus 0.25 and 0.5, A. nidulans 0.5 and 0.5, A. niger 0.25 and 0.25, A. terreus 0.25 and 0.5, and A. versicolor 0.25 and 0.5. Although caspofungin ECVs are not designed to predict the outcome of therapy, they may aid in the detection of strains with reduced antifungal susceptibility to this agent and acquired resistance mechanisms.
Antimicrobial Agents and Chemotherapy 03/2011; 55(6):2855-9. · 4.57 Impact Factor