Activity of voriconazole, itraconazole, fluconazole and amphotericin B in vitro against 1763 yeasts from 472 patients in the voriconazole phase III clinical studies

Johnson, Elizabeth; Espinel-Ingroff, Ana; Székely, Adrien; Hockey, Hans; Troke, Peter F.

doi:10.1016/j.ijantimicag.2008.05.023

Cited by 36 publications

(21 citation statements)

References 27 publications

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“…Overall, the voriconazole modes were lower (0.016 to 0.03 g/ml) than those of the other two azoles for most of the species, with the exception of C. glabrata and C. krusei (voriconazole modes, 0.06 and 0.12 g/ ml, respectively). Our MIC distributions are similar to those observed by other authors (33)(34)(35)(36)(37). Previously reported azole MICs for C. dubliniensis (fluconazole MIC 90 range, 8 to 32 g/ml) and C. guilliermondii (fluconazole MIC 90 range, 16 to 32 g/ml; voriconazole MIC 90 range, 4 to 8 g/ml) were higher than those observed in the present study (Tables 1 to 3).…”

Section: Resultssupporting

confidence: 91%

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

Espinel-Ingroff

Pfaller

Bustamante

et al. 2014

Antimicrob Agents Chemother

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uAlthough epidemiological cutoff values (ECVs) 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 (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 g/ml for C. albicans, 0.5, 0.25, and 0.03 g/ml for C. dubliniensis, 8, 1, and 0.25 g/ml for C. glabrata, 8, 0.5, and 0.12 g/ml for C. guilliermondii, 32, 0.5, and 0.25 g/ml for C. krusei, 1, 0.06, and 0.06 g/ml for C. lusitaniae, 1, 0.25, and 0.03 g/ml for C. parapsilosis, and 1, 0.12, and 0.06 g/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.

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Section: Resultssupporting

confidence: 91%

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

Espinel-Ingroff

Pfaller

Bustamante

et al. 2014

Antimicrob Agents Chemother

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“…There is no lack of data concerning the in vitro susceptibility of isolates of C. albicans, C. glabrata, C. tropicalis, and C. parapsilosis to both fluconazole and voriconazole (24,55). Longitudinal surveillance studies from individual institutions, cities, countries, and broad geographic regions document the sustained activities of these agents versus C. albicans, C. tropicalis, and C. parapsilosis and the ongoing potential for C. glabrata to develop resistance to both triazoles (2,10,12,17,27,46,55,63).…”

Section: Discussionmentioning

confidence: 99%

Results from the ARTEMIS DISK Global Antifungal Surveillance Study, 1997 to 2007: a 10.5-Year Analysis of Susceptibilities of Candida Species to Fluconazole and Voriconazole as Determined by CLSI Standardized Disk Diffusion

Pfaller¹,

Diekema

Gibbs³

et al. 2010

J Clin Microbiol

601

507

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.2% of Candida isolates tested were susceptible (S) to fluconazole; however, 13 of 31 species identified exhibited decreased susceptibility (<75% S), similar to that seen with the resistant (R) species C. glabrata and C. krusei. Among 197,619 isolates of Candida spp. tested against voriconazole, 95.0% were S and 3% were R. About 30% of fluconazole-R isolates of C. albicans, C. glabrata, C. tropicalis, C. rugosa, C. lipolytica, C. pelliculosa, C. apicola, C. haemulonii, C. humicola, C. lambica, and C. ciferrii remained S to voriconazole. An increase in fluconazole resistance over time was seen with C. parapsilosis, C. guilliermondii, C. lusitaniae, C. sake, and C. pelliculosa. Among the emerging fluconazole-R species were C. guilliermondii (11.4% R), C. inconspicua (53.2% R), C. rugosa (41.8% R), and C. norvegensis (40.7% R). The rates of isolation of C. rugosa, C. inconspicua, and C. norvegensis increased by 5-to 10-fold over the 10.5-year study period. C. guilliermondii and C. rugosa were most prominent in Latin America, whereas C. inconspicua and C. norvegensis were most common in Eastern European countries. This survey identifies several less-common species of Candida with decreased susceptibility to azoles. These organisms may pose a future threat to optimal antifungal therapy and underscore the importance of prompt and accurate species identification and antifungal susceptibility testing.Antifungal susceptibility testing is playing an increasing role as a means to track the development of antifungal resistance in epidemiological studies (2, 10, 12, 17, 27, 45-47, 55, 63). One of the important by-products of the standardization of antifungal susceptibility testing has been the ability to conduct surveillance for antifungal resistance using uniform methods (44). Meaningful large-scale surveys of antifungal susceptibility and resistance conducted over time would not be possible without a standardized broth microdilution (BMD) or disk diffusion (DD) method for performing the in vitro studies (12,38,60). Global surveillance programs such as the ARTEMIS antifungal surveillance program for DD testing (49,57,60) and MIC testing (12, 13), the European Confederation of Medical Mycology (ECMM) survey of candidemia (68), and the SENTRY Antifungal Surveillance Program (36-38) promote the use of standardized DD and BMD methods and provide useful and consistent antifungal susceptibility data from a broad international network of hospitals and laboratories.The ARTEMIS global antifungal surveillance program is among the most comprehensive and long-running fungal surveillance programs (12,45,57,58,60). The ARTEMIS program was designed to address many of the potential limitations of resistance surveillance studies (26): (i) it is both longitudinal (1997 to present) and global (142 participating sites in 41 countries) in scope, (ii) it employs standardized DD (7) and BMD (9) antifungal susceptibility test methods, (iii) both internal quality control (QC) performed in each participating laboratory and external quality assurance...

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“…Tables 1 and 2). The set included 150 resistant and 72 susceptible dose-dependent isolates (at 48 h) to voriconazole; some of these isolates were recovered from patients enrolled in the phase III voriconazole clinical trials (13), as well as from other patients. The CLSI QC isolates C. parapsilosis ATCC 22019 and C. krusei ATCC 6258 were tested each time a set of clinical isolates was evaluated in each laboratory; voriconazole and fluconazole MIC results were within the established QC MIC limits (5,6).…”

Section: Methodsmentioning

confidence: 99%

Comparison of 24-Hour and 48-Hour Voriconazole MICs as Determined by the Clinical and Laboratory Standards Institute Broth Microdilution Method (M27-A3 Document) in Three Laboratories: Results Obtained with 2,162 Clinical Isolates of Candida spp. and Other Yeasts

et al. 2009

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We evaluated the performance of the 24-h broth microdilution voriconazole MIC by obtaining MICs for 2,162 clinical isolates of Candida spp. and other yeasts; the 24-h results were compared to 48-h reference MICs to assess essential, as well as categorical, agreement. Although the overall essential agreement was 88.6%, it ranged from 96.4 to 100% for 6 of the 11 species or groups of yeasts tested. The overall categorical agreement was 93.2%, and it was above 90% for eight species. However, unacceptable percentages of very major errors (false susceptibility) were observed for Candida albicans (2.7%), C. glabrata (4.1%), C. tropicalis (9.7%), and other less common yeast species (9.8%). Since it is essential to identify potentially resistant isolates and breakpoints are based on 48-h MICs, it appears that the 24-h MIC is not as clinically useful as the 48-h reference MIC. However, further characterization of these falsely susceptible MICs for three of the four common Candida spp. is needed to understand whether these errors are due to trailing misinterpretation or if the 48-h incubation is required to detect voriconazole resistance. Either in vivo versus in vitro correlations or the determination of resistance mechanisms should be investigated.Candida spp. and Aspergillus spp. are responsible for the majority (80 to 90%) of fungal infections. During the last several years, new antifungal agents (echinocandins and triazoles) have been licensed for the systemic treatment of fungal infections. Among the triazoles, voriconazole is available for the oral or intravenous treatment of mold and yeast infections (e.g., primary treatment of invasive candidiasis, including candidemia, in neutropenic and nonneutropenic patients). These events have underscored the need for testing the antifungal susceptibilities of fungal pathogens to these agents. The Clinical and Laboratory Standards Institute (CLSI) has developed reference methods (CLSI M27-A3 and M44-A documents) for antifungal susceptibility testing of Candida spp. and Cryptococcus neoformans (3,5,6). In addition to the guidelines for testing voriconazole, the CLSI has established interpretive breakpoints for this agent versus Candida spp. (5,6,19). These microdilution MIC breakpoints were based on the determination of voriconazole MICs after 48 h of incubation. However, most common Candida spp. have suitable growth for MIC determination at 24 h; a shorter incubation time is more efficient and practical for use in the clinical laboratory and is currently used to determine endpoints for the echinocandins, amphotericin B, and fluconazole. The interlaboratory reproducibility of the 24-h voriconazole result, as well as the categorical agreement between 24-and 48-h MICs were previously addressed in a collaborative study for a small number of Candida isolates (8). The purpose of the present study was to further evaluate the suitability of CLSI 24 h voriconazole MIC results with 2,162 clinical isolates of Candida and other yeast species. The evaluation involved (i) the compatibilit...

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Activity of voriconazole, itraconazole, fluconazole and amphotericin B in vitro against 1763 yeasts from 472 patients in the voriconazole phase III clinical studies

Cited by 36 publications

References 27 publications

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

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

Results from the ARTEMIS DISK Global Antifungal Surveillance Study, 1997 to 2007: a 10.5-Year Analysis of Susceptibilities of Candida Species to Fluconazole and Voriconazole as Determined by CLSI Standardized Disk Diffusion

Comparison of 24-Hour and 48-Hour Voriconazole MICs as Determined by the Clinical and Laboratory Standards Institute Broth Microdilution Method (M27-A3 Document) in Three Laboratories: Results Obtained with 2,162 Clinical Isolates of Candida spp. and Other Yeasts

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