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 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 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 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 Establishing Genotypic Cutoff Values To Measure Antimicrobial Resistance in Salmonella

2016 ◽  
Vol 61 (3) ◽  
Author(s):  
Gregory H. Tyson ◽  
Shaohua Zhao ◽  
Cong Li ◽  
Sherry Ayers ◽  
Jonathan L. Sabo ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Large Scale ◽  
Acquired Resistance ◽  
Resistance Mechanisms ◽  
Wild Type ◽  
Content Type ◽  
Phenotypic Resistance ◽  
Large Scale Assessment ◽  
Resistance Determinants ◽  
Cutoff Values

ABSTRACT Whole-genome sequencing (WGS) has transformed our understanding of antimicrobial resistance, helping us to better identify and track the genetic mechanisms underlying phenotypic resistance. Previous studies have demonstrated high correlations between phenotypic resistance and the presence of known resistance determinants. However, there has never been a large-scale assessment of how well resistance genotypes correspond to specific MICs. We performed antimicrobial susceptibility testing and WGS of 1,738 nontyphoidal Salmonella strains to correlate over 20,000 MICs with resistance determinants. Using these data, we established what we term genotypic cutoff values (GCVs) for 13 antimicrobials against Salmonella. For the drugs we tested, we define a GCV as the highest MIC of isolates in a population devoid of known acquired resistance mechanisms. This definition of GCV is distinct from epidemiological cutoff values (ECVs or ECOFFs), which currently differentiate wild-type from non-wild-type strains based on MIC distributions alone without regard to genetic information. Due to the large number of isolates involved, we observed distinct MIC distributions for isolates with different resistance gene alleles, including for ciprofloxacin and tetracycline, suggesting the potential to predict MICs based on WGS data alone.

scholarly journals Interlaboratory Variability of Caspofungin MICs for Candida spp. Using CLSI and EUCAST Methods: Should the Clinical Laboratory Be Testing This Agent?

2013 ◽  
Vol 57 (12) ◽  
pp. 5836-5842 ◽  
Author(s):  
A. Espinel-Ingroff ◽  
M. C. Arendrup ◽  
M. A. Pfaller ◽  
L. X. Bonfietti ◽  
B. Bustamante ◽  
...  
Keyword(s):  
Storage Time ◽  
Clinical Laboratory ◽  
The United States ◽  
Candida Spp ◽  
Routine Testing ◽  
Content Type ◽  
Interlaboratory Variability ◽  
Clinical Breakpoints ◽  
Species Specific ◽  
Excessive Number

ABSTRACTAlthough Clinical and Laboratory Standards Institute (CLSI) clinical breakpoints (CBPs) are available for interpreting echinocandin MICs forCandidaspp., epidemiologic cutoff values (ECVs) based on collective MIC data from multiple laboratories have not been defined. While collating CLSI caspofungin MICs for 145 to 11,550Candidaisolates 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 to 0.5 μg/ml forC. albicansandC. tropicalis, 0.031 to 0.5 μg/ml forC. glabrata, and 0.063 to 1 μg/ml forC. krusei. Variability was also similar among MIC distributions forC. dubliniensisandC. lusitaniae. The exceptions wereC. parapsilosisandC. guilliermondiiMIC distributions, where most modes were within one 2-fold dilution of each other. These findings were consistent with available data from the European Committee on Antimicrobial Susceptibility Testing (EUCAST) (403 to 2,556 MICs) forC. albicans,C. glabrata,C. krusei, andC. 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) isolates (e.g.,C. glabrataandC. krusei) as either non-WT or resistant isolates. Until this problem is resolved, routine testing or reporting of CLSI caspofungin MICs forCandidais not recommended; micafungin or anidulafungin data could be used instead.

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

2011 ◽  
Vol 55 (6) ◽  
pp. 2855-2859 ◽  
Author(s):  
A. Espinel-Ingroff ◽  
A. Fothergill ◽  
J. Fuller ◽  
E. Johnson ◽  
T. Pelaez ◽  
...  
Keyword(s):  
Antifungal Susceptibility ◽  
Acquired Resistance ◽  
The United States ◽  
Resistance Mechanisms ◽  
Broth Microdilution ◽  
Wild Type ◽  
Content Type ◽  
Microdilution Method ◽  
Cutoff Values ◽  
Broth Microdilution Method

ABSTRACTClinical breakpoints have not been established for mold testing. Epidemiologic cutoff values (ECVs) are available for sixAspergillusspp. 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 sixAspergillusspp. and caspofungin. The number of available isolates was as follows: 1,691A. fumigatus, 432A. flavus, 192A. nidulans, 440A. niger, 385A. terreus, and 75A. versicolorisolates. 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 forA. fumigatus0.5 and 1,A. flavus0.25 and 0.5,A. nidulans0.5 and 0.5,A. niger0.25 and 0.25,A. terreus0.25 and 0.5, andA. versicolor0.25 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.

scholarly journals Antimicrobial Susceptibility Testing and Tentative Epidemiological Cutoff Values for FiveBacillusSpecies Relevant for Use as Animal Feed Additives or for Plant Protection

2018 ◽  
Vol 84 (19) ◽  
Author(s):  
Yvonne Agersø ◽  
Birgitte Stuer-Lauridsen ◽  
Karin Bjerre ◽  
Michelle Geervliet Jensen ◽  
Eric Johansen ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Resistance Genes ◽  
Pathogenic Bacteria ◽  
Animal Feed ◽  
Bacterial Species ◽  
Feed Additives ◽  
Content Type ◽  
Cutoff Values ◽  
Antimicrobial Resistance Genes ◽  
Species Specific

ABSTRACTBacillus megaterium(n= 29),Bacillus velezensis(n= 26),Bacillus amyloliquefaciens(n= 6),Bacillus paralicheniformis(n= 28), andBacillus licheniformis(n= 35) strains from different sources, origins, and time periods were tested for the MICs for nine antimicrobial agents by the CLSI-recommended method (Mueller-Hinton broth, 35°C, for 18 to 20 h), as well as with a modified CLSI method (Iso-Sensitest [IST] broth, 37°C [35°C forB. megaterium], 24 h). This allows a proposal of species-specific epidemiological cutoff values (ECOFFs) for the interpretation of antimicrobial resistance in these species. MICs determined by the modified CLSI method were 2- to 16-fold higher than with the CLSI-recommended method for several antimicrobials. The MIC distributions differed between species for five of the nine antimicrobials. Consequently, use of the modified CLSI method and interpretation of resistance by use of species-specific ECOFFs is recommended. The genome sequences of all strains were determined and used for screening for resistance genes against the ResFinder database and for multilocus sequence typing. A putative chloramphenicol acetyltransferase (cat) gene was found in oneB. megateriumstrain with an elevated chloramphenicol MIC compared to the otherB. megateriumstrains. InB. velezensisandB. amyloliquefaciens, a putative tetracycline efflux gene,tet(L), was found in all strains (n= 27) with reduced tetracycline susceptibility but was absent in susceptible strains. AllB. paralicheniformisand 23% ofB. licheniformisstrains had elevated MICs for erythromycin and harboredermD. The presence of these resistance genes follows taxonomy suggesting they may be intrinsic rather than horizontally acquired. Reduced susceptibility to chloramphenicol, streptomycin, and clindamycin could not be explained in all species.IMPORTANCEWhen commercializing bacterial strains, likeBacillusspp., for feed applications or plant bioprotection, it is required that the strains are free of acquired antimicrobial resistance genes that could potentially spread to pathogenic bacteria, thereby adding to the pool of resistance genes that may cause treatment failures in humans or animals. Conversely, if antimicrobial resistance is intrinsic to a bacterial species, the risk of spreading horizontally to other bacteria is considered very low. Reliable susceptibility test methods and interpretation criteria at the species level are needed to accurately assess antimicrobial resistance levels. In the present study, tentative ECOFFs for fiveBacillusspecies were determined, and the results showed that the variation in MICs followed the respective species. Moreover, putative resistance genes, which were detected by whole-genome sequencing and suggested to be intrinsic rather that acquired, could explain the resistance phenotypes in most cases.

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.

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