Use of Micafungin as a Surrogate Marker To Predict Susceptibility and Resistance to Caspofungin among 3,764 Clinical Isolates of Candida by Use of CLSI Methods and Interpretive Criteria

Pfaller, Michael A.; Messer, S. A.; Diekema, Daniel J.; Jones, Ronald N.; Castanheira, Mariana

doi:10.1128/jcm.02481-13

Cited by 66 publications

(39 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The recently reported YeastOne caspofungin epidemiological cutoff values (ECVs) were used to classify isolates as wild-type or non-wild-type isolates in this colorimetric assay (9). The rates of very major errors (VME), major errors (ME), and minor errors (mE) were also determined according to accepted definitions (10,11). Geometric mean (GM) MICs were calculated, and differences in GM MIC values among multiple groups were assessed for significance by analysis of variance (ANOVA) with Tukey's posttest for multiple comparisons.…”

Section: Discussionmentioning

confidence: 99%

Effects of Treated versus Untreated Polystyrene on Caspofungin In Vitro Activity against Candida Species

et al. 2016

View full text Add to dashboard Cite

Significant interlaboratory variability is observed in testing the caspofungin susceptibility of Candida species by both the CLSI and EUCAST broth microdilution methodologies. We evaluated the influence of treated versus untreated polystyrene microtiter trays on caspofungin MICs using 209 isolates of four Candida species, including 16 C. albicans and 11 C. glabrata isolates with defined FKS mutations. Caspofungin MICs were also determined using the commercially available YeastOne and Etest assays and 102 isolates. All C. glabrata isolates had caspofungin MICs of >0.5 g/ml, the clinical breakpoint for caspofungin resistance in this species, measured using trays made of treated polystyrene, regardless of the FKS status. In contrast, susceptible isolates could readily be distinguished from resistant/non-wild-type isolates when caspofungin MICs were measured using untreated polystyrene trays and both the YeastOne and Etest assays. Similar results were also observed for C. krusei isolates, as all isolates had caspofungin MICs above the threshold for resistance measured using treated polystyrene trays. In contrast, C. albicans isolates could be correctly identified as susceptible or resistant when caspofungin MICs were measured with treated or untreated trays and with the YeastOne and Etest assays. MICs falsely elevated above the resistance breakpoint were also not observed for C. tropicalis isolates. These results demonstrated that the use of treated polystyrene may be one factor that leads to falsely elevated caspofungin in vitro susceptibility results and that this may also be a greater issue for some Candida species than for others. Significant interlaboratory variability has been reported for caspofungin susceptibility testing, with some laboratories reporting MIC values elevated above the revised CLSI clinical breakpoints (1). The interlaboratory variability is not without consequences, as it may result in major errors for caspofungin use (i.e., falsely interpreting an isolate as resistant to this echinocandin). In a retrospective review of our antifungal susceptibility database using data from 2008 to 2012, we found that 95.6% of C. glabrata and 74.3% of C. krusei isolates would be classified as resistant to caspofungin on the basis of the revised CLSI echinocandin clinical breakpoints (2). Other laboratories have reported similar results (3). As the factors that lead to interlaboratory variability are unknown, we sought to determine if the choice of plastic used in the microtiter trays, either treated or untreated polystyrene, could affect caspofungin MIC values. These trays are designed for cell cultures, and treatment of the plastic, either by coating or corona discharge to impart an electrical charge to the plastic, allows the cells to adhere. Our laboratory has historically used 96-well microtiter trays made of treated polystyrene, while other laboratories have used those made of untreated plastic. The CLSI M27-A3 standard for yeast antifungal susceptibility testing has not addressed plastic type or recomm...

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of Treated versus Untreated Polystyrene on Caspofungin In Vitro Activity against Candida Species

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Numerous in vitro studies document comparable activities of these agents against a broad range of Candida species when tested using the broth microdilution methods of the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) (4)(5)(6)(7)(8)(9)(10). Both the CLSI and EUCAST have established clinical MIC breakpoints (CBPs) and epidemiological cutoff values (ECVs) for anidulafungin and micafungin tests against common species of Candida (10)(11)(12).…”

mentioning

confidence: 99%

Use of Anidulafungin as a Surrogate Marker To Predict Susceptibility and Resistance to Caspofungin among 4,290 Clinical Isolates of Candida by Using CLSI Methods and Interpretive Criteria

et al. 2014

Self Cite

View full text Add to dashboard Cite

bThis study addressed the application of anidulafungin as a surrogate marker to predict the susceptibility of Candida to caspofungin due to unacceptably high interlaboratory variation of caspofungin MIC values. CLSI reference broth microdilution methods and species-specific interpretive criteria were used to test 4,290 strains of Candida (eight species), including 71 strains with documented fks mutations. Caspofungin MIC values were compared with those of anidulafungin to determine the percentage of categorical agreement (CA) and very major (VME), major (ME), and minor error rates, as well as the ability to detect fks mutants. For all 4,290 isolates the CA was 97.1% (0.2% VME and ME, 2.5% minor errors) using anidulafungin as the surrogate. Among the 62 isolates of Candida albicans (4 isolates), C. tropicalis (5 isolates), C. krusei (4 isolates), C. kefyr (2 isolates), and C. glabrata (47 isolates) that were nonsusceptible (NS; either intermediate [I] or resistant [R]) to both caspofungin and anidulafungin, 52 (83.8%) contained a mutation in fks1 or fks2. Eight mutants of C. glabrata, two of C. albicans, and one each of C. tropicalis and C. krusei were classified as susceptible (S) to both antifungal agents. The remaining 7 mutants (2 C. albicans and 5 C. glabrata) were susceptible to one of the agents and either intermediate or resistant to the other. Using the epidemiological cutoff value (ECV) of 0.12 g/ml for both caspofungin and anidulafungin to differentiate wild-type (WT) from non-WT strains of C. glabrata, 42 of the 55 (76.4%) C. glabrata mutants were non-WT and 8 of the 55 (14.5%) were WT for both agents (90.9% concordance). Anidulafungin can accurately serve as a surrogate marker to predict S and R of Candida to caspofungin.

show abstract

“…According to the newest EUCAST antifungal clinical breakpoint table, "EUCAST breakpoints have not yet been established for caspofungin, due to significant interlaboratory variation in MIC ranges for caspofungin" (33). However, Pfaller and colleagues recommend testing anidulafungin and micafungin for predicting caspofungin MIC (26,34). Sensititre YeastOne (SYO; TREK Diagnostic Systems), a well-described colorimetric antifungal panel that includes itraconazole in addition to the 8 antifungal agents included in SQ, is already equipped with 11 dilution steps, e.g., for CAS, 0.008 to 8 g/ml.…”

Section: Discussionmentioning

confidence: 99%

“…Comparisons of the performance of SQ and SYO have not yet been reported and should be determined. However, several studies have reported that the SYO method achieves excellent results in terms of reproducibility and CAs with both the EUCAST BMD protocol and the CLSI broth microdilution reference method (19,20,32,(34)(35)(36).…”

Section: Discussionmentioning

confidence: 99%

Comparative Evaluation of a New Commercial Colorimetric Microdilution Assay (SensiQuattro Candida EU) with MIC Test Strip and EUCAST Broth Microdilution Methods for Susceptibility Testing of Invasive Candida Isolates

et al. 2015

View full text Add to dashboard Cite

Candidemia is an important cause of morbidity and mortality in immunosuppressed patients. Candida isolates must be cultivated, identified, and tested for susceptibility. We compared the performance of a new colorimetric broth microdilution panel (SensiQuattro Candida EU) for antifungal susceptibility testing to that of Liofilchem's MIC test strip and the EUCAST reference broth microdilution protocol. We tested 187 blood culture isolates of 5 Candida spp. (120 C. albicans, 38 C. glabrata, 10 C. parapsilosis, 12 C. tropicalis, and 7 C. krusei) against seven antifungal agents (amphotericin B, fluconazole, voriconazole, posaconazole, caspofungin, anidulafungin, and micafungin) and interpreted the MICs according to the EUCAST recommendations. If applicable, the overall essential agreement (EA) of the SensiQuattro panel with the reference broth microdilution was slightly higher for C. albicans (87%) than for other species (85.8%). We found that SensiQuattro performed best in testing amphotericin B (EA, 100%), voriconazole (EA, 93.7%), and posaconazole (EA, 94.8%) against C. albicans, but its error rate for this species was high (29.6%) because of mainly major errors (26.7%) in testing anidulafungin and micafungin. Compared to the SensiQuattro panel, the MIC test strip exhibited a higher level of agreement for most isolates. SensiQuattro assays are easy to perform, but they are currently not suitable for testing echinocandins against Candida spp. Bloodstream infections caused by Candida spp. are the most common invasive fungal infections (1, 2). Patients at risk of candidemia are those who are immunocompromised, e.g., those with hematologic and solid-organ malignancies, those receiving immunosuppressive therapy, those with chronic renal failure, and those treated with antibiotics or invasive catheters (2, 3). In the population of the United States, the incidence of hospital-acquired candidemia is as high as 10 cases per 100,000 patients (4). The 2013 annual epidemiological report of the European Centre for Disease Prevention and Control (ECDC) stated that Candida spp. are the fifth most frequently isolated microorganism in intensive care unit (ICU)-acquired bloodstream infections in the European Union (5). Mortality rates due to Candida bloodstream infections vary from 45% to 53% depending on the population investigated (6, 7). Although C. albicans is still the most frequently isolated Candida species in candidemia, non-albicans Candida species are increasingly found to be the causative agents (8-12).Of particular concern is emerging resistance to both the antifungal classes of azoles and the newer echinocandins, as recently reported in the World Health Organization's "Antimicrobial Resistance: Global Report on Surveillance 2014" (13). Resistance to antifungal drugs varies among the various species of Candida because of the intrinsically low susceptibility of C. glabrata to azole antifungals, such as fluconazole (FLC) (14), and because of multifactorial processes or mutations in the fks1 and fks2 genes (15,16). For the...

show abstract

Use of Micafungin as a Surrogate Marker To Predict Susceptibility and Resistance to Caspofungin among 3,764 Clinical Isolates of Candida by Use of CLSI Methods and Interpretive Criteria

Cited by 66 publications

References 43 publications

Effects of Treated versus Untreated Polystyrene on Caspofungin In Vitro Activity against Candida Species

Effects of Treated versus Untreated Polystyrene on Caspofungin In Vitro Activity against Candida Species

Use of Anidulafungin as a Surrogate Marker To Predict Susceptibility and Resistance to Caspofungin among 4,290 Clinical Isolates of Candida by Using CLSI Methods and Interpretive Criteria

Comparative Evaluation of a New Commercial Colorimetric Microdilution Assay (SensiQuattro Candida EU) with MIC Test Strip and EUCAST Broth Microdilution Methods for Susceptibility Testing of Invasive Candida Isolates

Contact Info

Product

Resources

About