Search

ABSTRACTAlthough epidemiological cutoff values (ECVs) have been established for Candidaspp. and the triazoles, they are based on MIC data from a single laboratory. We have established ECVs for eight Candidaspecies and fluconazole, posaconazole, and voriconazole based on wild-type (WT) MIC distributions for isolates of C. 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), and C. 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 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 (harboring mutations in or upregulation of ERG11, MDR1, CDR1, or CDR2) and 64 WT isolates indicated that our ECVs may be useful in distinguishing WT from non-WT isolates. more...

ABSTRACTSince epidemiological cutoff values (ECVs) using CLSI MICs from multiple laboratories are not available for Candidaspp. 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 8,210 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. 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 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 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 (no fksmutations) and 51 isolates with fksmutations, the species-specific ECVs for anidulafungin and micafungin correctly classified 47 (92.2%) and 51 (100%) of the fksmutants, respectively, as non-WT strains. These ECVs may aid in detecting non-WT isolates with reduced susceptibility to anidulafungin and micafungin due to fksmutations. more...

ABSTRACTAlthough Clinical and Laboratory Standards Institute (CLSI) clinical breakpoints (CBPs) are available for interpreting echinocandin MICs for Candidaspp., 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 Candidaisolates 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 for C. albicansand C. tropicalis, 0.031 to 0.5 μg/ml for C. glabrata, and 0.063 to 1 μg/ml for C. krusei. Variability was also similar among MIC distributions for C. dubliniensisand C. lusitaniae. The exceptions were C. parapsilosisand C. 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) 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) isolates (e.g., C. glabrataand C. krusei) as either non-WT or resistant isolates. Until this problem is resolved, routine testing or reporting of CLSI caspofungin MICs for Candidais not recommended; micafungin or anidulafungin data could be used instead. more...

ABSTRACTEpidemiological cutoff values (ECVs) for the Cryptococcus neoformans-Cryptococcus gattiispecies 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. neoformanswere 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. gattiinontyped, VGI, VGIIa, and VGIII), 16 μg/ml (C. neoformansnontyped, VNIII, and VGIV), and 32 μg/ml (VGII); itraconazole, 0.25 μg/ml (VNI), 0.5 μg/ml (C. neoformansand C. gattiinontyped and VGI to VGIII), and 1 μg/ml (VGIV); posaconazole, 0.25 μg/ml (C. neoformansnontyped and VNI) and 0.5 μg/ml (C. gattiinontyped and VGI); and voriconazole, 0.12 μg/ml (VNIV), 0.25 μg/ml (C. neoformansand C. gattiinontyped, 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. more...

ABSTRACTDuring a 2-year surveillance program (1996 to 1998) in Quebec, Canada, 442 strains of Candidaspecies were isolated from 415 patients in 51 hospitals. The distribution of species was as follows: Candida albicans,54%; C. glabrata,15%; C. parapsilosis,12%; C. tropicalis,9%; C. lusitaniae,3%; C. krusei,3%; and Candidaspp., 3%. These data, compared to those of a 1985 survey, indicate variations in species distribution, with the proportions of C. glabrataandC. parapsilosisincreasing by 9 and 4%, respectively, and those of C. albicansand C. tropicalisdecreasing by 10 and 7%, respectively. However, these differences are statistically significant for C. glabrataand C. tropicalisonly. MICs of amphotericin B were =4 µg/ml for 3% of isolates, all of which were non-C. albicansspecies. Three percent of C. albicansisolates were resistant to flucytosine (=32 µg/ml). Resistance to itraconazole (=1 µg/ml) and fluconazole (=64 µg/ml) was observed, respectively, in 1 and 1% of C. albicans, 14 and 9% of C. glabrata, 5 and 0% of C. tropicalis,and 0% of C. parapsilosisandC. lusitaniaeisolates. Clinical data were obtained for 343 patients. The overall crude mortality rate was 38%, reflecting the multiple serious underlying illnesses found in these patients. Bloodstream infections were documented for 249 patients (73%). Overall, systemic triazoles had been administered to 10% of patients before the onset of candidiasis. The frequency of isolation of non-C. albicansspecies was significantly higher in this group of patients. Overall, only two C. albicansisolates were found to be resistant to fluconazole. These were obtained from an AIDS patient and a leukemia patient, both of whom had a history of previous exposure to fluconazole. At present, it appears that resistance to fluconazole in Quebec is rare and is restricted to patients with prior prolonged azole treatment. more...

PURPOSE: To describe the frequency, characteristics and impact of invasive fungal infection in Canada.METHODS: Nominal case reporting with standardized data collection from selected sites across Canada. Cases were found primarily through laboratory review with supplementation by record review and clinical surveillance at some sites.RESULTS: The frequency of invasive fungal infection varied from 3.54 to 6.64/100,000 population per year. Candida species were responsible for 66% of all reports; 80% of candidal infections were bloodstream isolates. Crytococcus neoformans, Aspergillus species and Histoplasma capsulatum each accounted for 5% to 10% of cases, and all other organisms less than 5% each. Human immunodeficiency virus infection was an important comorbidity for cryptococcus and histoplasma infections, and was associated with increased mortality for only histoplasma infections. Geographical variation of histoplasma, blastomyces and coccidioidomyces infection was confirmed. Case fatality was high for all invasive fungal infections, except coccidioidomycosis, blastomycosis and sporotrichosis.CONCLUSIONS: Candida species infections are the major pathogens in invasive fungal infections in Canada; all other species occur relatively infrequently. The potential for therapeutic intervention to limit mortality requires further assessment. more...