The Experts below are selected from a list of 498 Experts worldwide ranked by ideXlab platform
M A Pfaller - One of the best experts on this subject based on the ideXlab platform.
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global trends in the antifungal susceptibility of cryptococcus neoformans 1990 to 2004
Journal of Clinical Microbiology, 2005Co-Authors: M A Pfaller, R J Hollis, S A Messer, Gary V Doern, L Boyken, C Rice, S Tendolkar, Daniel J DiekemaAbstract:The antifungal susceptibilities of 1,811 clinical isolates of Cryptococcus neoformans obtained from 100 laboratories in 5 geographic regions worldwide between 1990 and 2004 were determined. The MICs of amphotericin B, flucytosine, fluconazole, voriconazole, posaconazole, and Ravuconazole were determined by the National Committee for Clinical Laboratory Standards broth microdilution method. Isolates were submitted to a central reference laboratory (University of Iowa) from study centers in Africa (5 centers, 395 isolates), Europe (14 centers, 102 isolates), Latin America (14 centers, 82 isolates), the Pacific region (7 centers, 50 isolates), and North America (60 centers, 1,182 isolates). Resistance to amphotericin B, flucytosine, and fluconazole was ≤1% overall. Susceptibility to flucytosine (MIC, ≤4 μg/ml) ranged from 35% in North America to 68% in Latin America. Similarly, only 75% of isolates from North America were susceptible to fluconazole (MIC, ≤8 μg/ml) compared to 94 to 100% in the other regions. Isolates remained highly susceptible to amphotericin B (99% susceptibility at a MIC of ≤1 μg/ml) over the entire 15-year period. Susceptibility to flucytosine (MIC, ≤4 μg/ml) increased from 34% in 1990 to 1994 to 66% in 2000 to 2004. Susceptibility to fluconazole (MIC, ≤8 μg/ml) increased from 72% in 1990 to 1994 to 96% in 2000 to 2004. Voriconazole, posaconazole, and Ravuconazole all were very active (99% of isolates susceptible at MIC of ≤1 μg/ml) against this geographically diverse collection of isolates. We conclude that in vitro resistance to antifungal agents used in the treatment of cryptococcosis remains uncommon among isolates of C. neoformans from five broad geographic regions and has not increased over a 15-year period.
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Activities of Available and Investigational Antifungal Agents against Rhodotorula Species
Journal of clinical microbiology, 2005Co-Authors: Daniel J Diekema, B. Petroelje, Shawn A. Messer, Richard J. Hollis, M A PfallerAbstract:Rhodotorula species are emerging pathogens in immunocompromised patients. We report the in vitro activities of eight antifungals against 64 Rhodotorula isolates collected in surveillance programs between 1987 and 2003. Rhodotorula strains are resistant in vitro to fluconazole (MIC at which 50% of the isolates tested are inhibited [MIC(50)], >128 microg/ml) and caspofungin (MIC(50), >8 microg/ml). Amphotericin B (MIC(50),1 microg/ml) and flucytosine (MIC(50), 0.12 microg/ml) are both active in vitro, and the new and investigational triazoles all have some in vitro activity, with Ravuconazole being the most active (MIC(50), 0.25 microg/ml).
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cross resistance between fluconazole and Ravuconazole and the use of fluconazole as a surrogate marker to predict susceptibility and resistance to Ravuconazole among 12 796 clinical isolates of candida spp
Journal of Clinical Microbiology, 2004Co-Authors: M A Pfaller, R J Hollis, S A Messer, L Boyken, C Rice, S Tendolkar, Daniel J DiekemaAbstract:Cross-resistance within a class of antimicrobial agents is a problem that is often encountered with antibacterial agents, and it is also an issue with antifungal agents. A current example is Ravuconazole, a new triazole antifungal with an expanded spectrum and potency against Candida spp., Aspergillus spp., and other opportunistic fungal pathogens. The present study addresses the issue of cross-resistance between fluconazole and Ravuconazole and the use of fluconazole as a surrogate marker to predict the susceptibility of Candida spp. to Ravuconazole. Reference broth microdilution MIC results for 12,796 strains of Candida spp. isolated from more than 200 medical centers worldwide were used. Ravuconazole MICs and tentative interpretive categories (susceptible, ≤1 μg/ml; resistant, ≥2 μg/ml) were compared with those of fluconazole by using regression statistics and error rate bounding analyses. For all 12,796 isolates, the absolute categorical agreement rate was 92.5% (rate of false-susceptible results, or very major errors [VME], 0.1%). Ravuconazole was active (MIC, ≤1 μg/ml) against 99.9% of the fluconazole-susceptible isolates, 96% of the fluconazole-susceptible dose-dependent isolates, and 49% of the fluconazole-resistant isolates, including 99% of the Candida krusei isolates. Since Ravuconazole is 16- to 32-fold more potent than fluconazole, the performance of fluconazole as a surrogate marker for Ravuconazole susceptibility was improved by designating those isolates with fluconazole MICs of ≤32 μg/ml susceptible to Ravuconazole, resulting in a categorical agreement rate of 98.3%, with a VME rate of 0.3% (99 and 0.4%, respectively, when C. krusei was omitted). Cross-resistance between fluconazole and Ravuconazole applies most directly to fluconazole-resistant Candida glabrata and is variable among other species of Candida. Fluconazole may serve as a surrogate marker to predict the susceptibility of Candida spp. to Ravuconazole.
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geographic variation in the susceptibilities of invasive isolates of candida glabrata to seven systemically active antifungal agents a global assessment from the artemis antifungal surveillance program conducted in 2001 and 2002
Journal of Clinical Microbiology, 2004Co-Authors: M A Pfaller, R J Hollis, S A Messer, L Boyken, S Tendolkar, Daniel J DiekemaAbstract:We examined the susceptibilities to amphotericin B, flucytosine, fluconazole, posaconazole, Ravuconazole, voriconazole, and caspofungin of 601 invasive isolates of Candida glabrata and grouped the isolates by geographic location: North America (331 isolates), Latin America (58 isolates), Europe (135 isolates), and Asia-Pacific (77 isolates). Caspofungin (MIC at which 90% of isolates tested are susceptible [MIC(90)], 0.12 microg/ml; 100% of strains are susceptible [S] at a MIC of triazoles were most active in the Asia-Pacific region (90 to 96.1% S) and least active in North America (82.5 to 90.3% S). All 46 isolates that were resistant to fluconazole were susceptible to caspofungin (MIC(90), 0.06 microg/ml) and flucytosine (MIC(90), 0.12 microg/ml) and exhibited variable cross-resistance to posaconazole, Ravuconazole, and voriconazole.
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multicenter comparison of the sensititre yeastone colorimetric antifungal panel with the nccls m27 a2 reference method for testing new antifungal agents against clinical isolates of candida spp
Journal of Clinical Microbiology, 2004Co-Authors: Ana Espinelingroff, M A Pfaller, S A Messer, C C Knapp, N M Holliday, S B KillianAbstract:A multicenter (three centers) study compared MICs obtained by the Sensititre YeastOne Colorimetric Antifungal plate to reference microdilution broth (NCCLS M27-A2 document) MICs of three new triazoles (posaconazole, Ravuconazole, and voriconazole) and the echinocandin caspofungin acetate for 100 isolates of Candida spp. In addition, amphotericin B and fluconazole were tested as control drugs. Colorimetric MICs of caspofungin and amphotericin B corresponded to the first blue well (no growth), and MICs of the other agents corresponded to the first slightly purple or blue well. Two comparisons of MIC pairs by the two methods were evaluated: 24-h colorimetric MICs were compared to NCCLS MICs at 24 and at 48 h. The interlaboratory reproducibility of YeastOne and reference MICs was also examined. The best performance of the YeastOne plate was with 24-h MICs (overall, 95 to 99% agreement) for all the species and antifungal agents. These results suggest the potential value of the YeastOne plate for use in the clinical laboratory for the four new antifungal agents evaluated.
S A Messer - One of the best experts on this subject based on the ideXlab platform.
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international surveillance of candida spp and aspergillus spp report from the sentry antimicrobial surveillance program 2003
Journal of Clinical Microbiology, 2006Co-Authors: S A Messer, Ronald N Jones, Thomas R FritscheAbstract:During 2003, a total of 1,397 Candida isolates, 73 Aspergillus isolates, 53 Cryptococcus neoformans isolates, and 25 other fungal isolates from infected, normally sterile, body sites in patients hospitalized in North America, Europe, and Latin America were studied as a component of the longitudinal SENTRY Antimicrobial Surveillance Program. The MICs for seven antifungal agents were determined in a central laboratory (JMI Laboratories, North Liberty, IA) using testing methods promulgated by the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards). The rank order of Candida spp. occurrence was as follows: C. albicans (48.7%), C. parapsilosis (17.3%), C. glabrata (17.2%), C. tropicalis (10.9%), C. krusei (1.9%), and other Candida spp. (4.0%). C. albicans accounted for 51.5, 47.8, and 36.5% of candidal infections in North America, Europe, and Latin America, respectively. Ravuconazole, voriconazole, and fluconazole were highly active against C. albicans, C. parapsilosis, and C. tropicalis, with both former agents being more potent (MIC at which 90% of the isolates tested are inhibited [MIC90] of ≤0.008 to 0.12 μg/ml) than fluconazole (MIC90 of 0.5 to 2 μg/ml). C. glabrata isolates were less susceptible to these agents, with MIC90s of 1, 1, and 64 μg/ml, respectively. Ravuconazole and voriconazole were the most active agents tested against C. krusei (MIC90 of 0.5 μg/ml). Among Aspergillus spp., A. fumigatus was the most commonly (71.2% of isolates) recovered species; 96.2, 96.2, 84.6, and 11.5% of strains were inhibited by ≤1 μg/ml of Ravuconazole, voriconazole, itraconazole, and amphotericin B, respectively. Of the antifungal agents tested, Ravuconazole and voriconazole displayed the greatest spectrum of activity against pathogenic Candida and Aspergillus spp., regardless of geographic origin. These results extend upon previous findings from SENTRY Program reports (1997 to 2000), further characterizing species composition as seen in local clinical practice and demonstrating the potent activity of selected, newer triazole antifungal agents.
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global trends in the antifungal susceptibility of cryptococcus neoformans 1990 to 2004
Journal of Clinical Microbiology, 2005Co-Authors: M A Pfaller, R J Hollis, S A Messer, Gary V Doern, L Boyken, C Rice, S Tendolkar, Daniel J DiekemaAbstract:The antifungal susceptibilities of 1,811 clinical isolates of Cryptococcus neoformans obtained from 100 laboratories in 5 geographic regions worldwide between 1990 and 2004 were determined. The MICs of amphotericin B, flucytosine, fluconazole, voriconazole, posaconazole, and Ravuconazole were determined by the National Committee for Clinical Laboratory Standards broth microdilution method. Isolates were submitted to a central reference laboratory (University of Iowa) from study centers in Africa (5 centers, 395 isolates), Europe (14 centers, 102 isolates), Latin America (14 centers, 82 isolates), the Pacific region (7 centers, 50 isolates), and North America (60 centers, 1,182 isolates). Resistance to amphotericin B, flucytosine, and fluconazole was ≤1% overall. Susceptibility to flucytosine (MIC, ≤4 μg/ml) ranged from 35% in North America to 68% in Latin America. Similarly, only 75% of isolates from North America were susceptible to fluconazole (MIC, ≤8 μg/ml) compared to 94 to 100% in the other regions. Isolates remained highly susceptible to amphotericin B (99% susceptibility at a MIC of ≤1 μg/ml) over the entire 15-year period. Susceptibility to flucytosine (MIC, ≤4 μg/ml) increased from 34% in 1990 to 1994 to 66% in 2000 to 2004. Susceptibility to fluconazole (MIC, ≤8 μg/ml) increased from 72% in 1990 to 1994 to 96% in 2000 to 2004. Voriconazole, posaconazole, and Ravuconazole all were very active (99% of isolates susceptible at MIC of ≤1 μg/ml) against this geographically diverse collection of isolates. We conclude that in vitro resistance to antifungal agents used in the treatment of cryptococcosis remains uncommon among isolates of C. neoformans from five broad geographic regions and has not increased over a 15-year period.
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cross resistance between fluconazole and Ravuconazole and the use of fluconazole as a surrogate marker to predict susceptibility and resistance to Ravuconazole among 12 796 clinical isolates of candida spp
Journal of Clinical Microbiology, 2004Co-Authors: M A Pfaller, R J Hollis, S A Messer, L Boyken, C Rice, S Tendolkar, Daniel J DiekemaAbstract:Cross-resistance within a class of antimicrobial agents is a problem that is often encountered with antibacterial agents, and it is also an issue with antifungal agents. A current example is Ravuconazole, a new triazole antifungal with an expanded spectrum and potency against Candida spp., Aspergillus spp., and other opportunistic fungal pathogens. The present study addresses the issue of cross-resistance between fluconazole and Ravuconazole and the use of fluconazole as a surrogate marker to predict the susceptibility of Candida spp. to Ravuconazole. Reference broth microdilution MIC results for 12,796 strains of Candida spp. isolated from more than 200 medical centers worldwide were used. Ravuconazole MICs and tentative interpretive categories (susceptible, ≤1 μg/ml; resistant, ≥2 μg/ml) were compared with those of fluconazole by using regression statistics and error rate bounding analyses. For all 12,796 isolates, the absolute categorical agreement rate was 92.5% (rate of false-susceptible results, or very major errors [VME], 0.1%). Ravuconazole was active (MIC, ≤1 μg/ml) against 99.9% of the fluconazole-susceptible isolates, 96% of the fluconazole-susceptible dose-dependent isolates, and 49% of the fluconazole-resistant isolates, including 99% of the Candida krusei isolates. Since Ravuconazole is 16- to 32-fold more potent than fluconazole, the performance of fluconazole as a surrogate marker for Ravuconazole susceptibility was improved by designating those isolates with fluconazole MICs of ≤32 μg/ml susceptible to Ravuconazole, resulting in a categorical agreement rate of 98.3%, with a VME rate of 0.3% (99 and 0.4%, respectively, when C. krusei was omitted). Cross-resistance between fluconazole and Ravuconazole applies most directly to fluconazole-resistant Candida glabrata and is variable among other species of Candida. Fluconazole may serve as a surrogate marker to predict the susceptibility of Candida spp. to Ravuconazole.
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geographic variation in the susceptibilities of invasive isolates of candida glabrata to seven systemically active antifungal agents a global assessment from the artemis antifungal surveillance program conducted in 2001 and 2002
Journal of Clinical Microbiology, 2004Co-Authors: M A Pfaller, R J Hollis, S A Messer, L Boyken, S Tendolkar, Daniel J DiekemaAbstract:We examined the susceptibilities to amphotericin B, flucytosine, fluconazole, posaconazole, Ravuconazole, voriconazole, and caspofungin of 601 invasive isolates of Candida glabrata and grouped the isolates by geographic location: North America (331 isolates), Latin America (58 isolates), Europe (135 isolates), and Asia-Pacific (77 isolates). Caspofungin (MIC at which 90% of isolates tested are susceptible [MIC(90)], 0.12 microg/ml; 100% of strains are susceptible [S] at a MIC of triazoles were most active in the Asia-Pacific region (90 to 96.1% S) and least active in North America (82.5 to 90.3% S). All 46 isolates that were resistant to fluconazole were susceptible to caspofungin (MIC(90), 0.06 microg/ml) and flucytosine (MIC(90), 0.12 microg/ml) and exhibited variable cross-resistance to posaconazole, Ravuconazole, and voriconazole.
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multicenter comparison of the sensititre yeastone colorimetric antifungal panel with the nccls m27 a2 reference method for testing new antifungal agents against clinical isolates of candida spp
Journal of Clinical Microbiology, 2004Co-Authors: Ana Espinelingroff, M A Pfaller, S A Messer, C C Knapp, N M Holliday, S B KillianAbstract:A multicenter (three centers) study compared MICs obtained by the Sensititre YeastOne Colorimetric Antifungal plate to reference microdilution broth (NCCLS M27-A2 document) MICs of three new triazoles (posaconazole, Ravuconazole, and voriconazole) and the echinocandin caspofungin acetate for 100 isolates of Candida spp. In addition, amphotericin B and fluconazole were tested as control drugs. Colorimetric MICs of caspofungin and amphotericin B corresponded to the first blue well (no growth), and MICs of the other agents corresponded to the first slightly purple or blue well. Two comparisons of MIC pairs by the two methods were evaluated: 24-h colorimetric MICs were compared to NCCLS MICs at 24 and at 48 h. The interlaboratory reproducibility of YeastOne and reference MICs was also examined. The best performance of the YeastOne plate was with 24-h MICs (overall, 95 to 99% agreement) for all the species and antifungal agents. These results suggest the potential value of the YeastOne plate for use in the clinical laboratory for the four new antifungal agents evaluated.
Juan L Rodrigueztudela - One of the best experts on this subject based on the ideXlab platform.
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development and validation of a fast hplc photodiode array detection method for the measurement of voriconazole in human serum samples a reference laboratory experience
Enfermedades Infecciosas Y Microbiologia Clinica, 2013Co-Authors: Emilio Cendejasbueno, Manuel Cuencaestrella, Juan L Rodrigueztudela, Alicia GomezlopezAbstract:The aim of this study was the development and validation of a fast and simple high performance liquid chromatography method for measuring voriconazole in human serum using Ravuconazole as an external standard. The experience of the reference laboratory in therapeutic drug monitoring of voriconazole is also reported. This method is based on the precipitation of proteins in human serum and detection by HPLC/UV. Chromatographic separation is achieved using an isocratic solvent delivery with detection at 255 nm and a run time of 7 min. The assay was validated according to international guidelines and was also applied to the analysis of 141 trough serum samples from patients treated with voriconazole. All validation parameters met the criteria set out in FDA guidelines for bioanalytical methods. A high interpatient and intrapatient variability was observed in clinical samples. This method is accurate enough to perform therapeutic drug monitoring in patients receiving voriconazole treatment.
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antifungal susceptibility profile in vitro of sporothrix schenckii in two growth phases and by two methods microdilution and e test
Mycoses, 2010Co-Authors: Maria Clara Gutierrezgalhardo, Juan L Rodrigueztudela, Araceli Monzon, Rosely Maria Zancopeoliveira, Manuel CuencaestrellaAbstract:The susceptibility profile of 91 Sporothrix schenckii isolates in both growth phases was determined by microdilution test (Antifungal Susceptibility Testing of the European Committee for Antimicrobial Susceptibility Testing; AFST-EUCAST). Amphotericin B (AMB), itraconazole (ITC), posaconazole, Ravuconazole and terbinafine were found active in vitro against both phases but minimum inhibitory concentrations values for mycelial phase were significantly higher. Fluconazole (FLC) and voriconazole (VRC) were inactive in vitro against both phases. The E-test technique was also performed with 41 representative isolates for AMB, FLC, ITC and VRC. Average agreement rates between yeast phase microdilution results and E-test results were high for AMB (77.5%) and FLC (87.8%), but low for ITC and VRC with rates of 56.4% and 54.5%, respectively. AFST-EUCAST is not the most recommended test to perform drug susceptibility testing of S. schenckii in clinical laboratories, and E-test could be an alternative methodology for this purpose, mainly when the activity in vitro of antifungal agents of AMB and FLC are evaluated.
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molecular identification and susceptibility testing of trichosporon isolates from a brazilian hospital
Revista Iberoamericana De Micologia, 2008Co-Authors: Mariceli Araujo Ribeiro, Ana Alastrueyizquierdo, Juan L Rodrigueztudela, Alicia Gomezlopez, Manuel CuencaestrellaAbstract:In this study the molecular identification and susceptibility profile of 21 clinical isolates, from a Brazilian hospital, belongs to six different species of Trichosporon were described. Trichosporon asahii was the predominant species and corresponded to 43% of isolates. Eighty three percent of the strains isolated from deep sites were identified as T. asahii, while only 17% belong to a non-T. asahii species (Trichosporon inkin). In general, the MICs were high and independent of the species of Trichosporon as well as the clinical origin of strain. Amphotericin B and fluconazole were less effective against Trichosporon spp. and high MIC values of voriconazole, posaconazole and Ravuconazole were observed. Fifty-six percent (5/9) of T. asahii strains were isolated from deep sites, whereas 8% (1/12) of non-T. asahii species were isolated from those sites. A total of 89% of T. asahii isolates exhibited resistance to amphotericin B in vitro.
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epidemiological cutoffs and cross resistance to azole drugs in aspergillus fumigatus
Antimicrobial Agents and Chemotherapy, 2008Co-Authors: Juan L Rodrigueztudela, Ana Alastrueyizquierdo, Araceli Monzon, Emilia Mellado, Laura Alcazarfuoli, Manuel CuencaestrellaAbstract:Antifungal susceptibility testing of molds has been standardized in Europe and in the United States. Aspergillus fumigatus strains with resistance to azole drugs have recently been detected and the underlying molecular mechanisms of resistance characterized. Three hundred and ninety-three isolates, including 32 itraconazole-resistant strains, were used to define wild-type populations, epidemiological cutoffs, and cross-resistance between azole drugs. The epidemiological cutoff for itraconazole, voriconazole, and Ravuconazole for the wild-type populations of A. fumigatus was ≤1 mg/liter. For posaconazole, the epidemiological cutoff was ≤0.25 mg/liter. Up till now, isolates susceptible to itraconazole have not yet displayed resistance to other azole drugs. Cross-resistance between azole drugs depends on specific mutations in cyp51A. Thus, a substitution of glycine in position 54 of Cyp51A confers cross-resistance between itraconazole and posaconazole. A substitution of methionine at position 220 or a duplication in tandem of a 34-bp fragment in the cyp51A promoter combined with a substitution of leucine at position 98 for histidine confers cross-resistance to all azole drugs tested. The results obtained in this study will help to develop clinical breakpoints for azole drugs and A. fumigatus.
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antifungal susceptibility profile of clinical fusarium spp isolates identified by molecular methods
Journal of Antimicrobial Chemotherapy, 2008Co-Authors: Ana Alastrueyizquierdo, Manuel Cuencaestrella, Araceli Monzon, Emilia Mellado, Juan L RodrigueztudelaAbstract:OBJECTIVES: To analyse the susceptibility pattern of a collection of Fusarium clinical isolates. METHODS: The antifungal susceptibility pattern of 67 isolates of Fusarium was analysed. Strains were identified by morphological and molecular methods by means of sequencing elongation factor alpha. RESULTS AND CONCLUSIONS: Six different species were identified. Fusarium solani was the most frequently isolated, followed by Fusarium oxysporum, Fusarium proliferatum and Fusarium verticilloides. Amphotericin B was the only drug with in vitro activity (range: 0.015-32 mg/L). The rest of the antifungals tested (itraconazole, voriconazole, Ravuconazole, posaconazole and terbinafine) showed very poor activity against Fusarium, confirming the multiresistant nature of this genus.
Rn Jones - One of the best experts on this subject based on the ideXlab platform.
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Clinical evaluation of the Sensititre YeastOne colorimetric antifungal plate for antifungal susceptibility testing of the new triazoles voriconazole, posaconazole
2004Co-Authors: M A Pfaller, A. Espinel-ingroff, Rn JonesAbstract:A commercially prepared dried colorimetric microdilution panel (Sensititre YeastOne, TREK Diagnostic Systems, Cleveland, Ohio) was compared in three different laboratories with the National Committee for Clinical Laboratory Standards (NCCLS) reference microdilution method by testing two quality control strains and 300 clinical isolates of Candida spp. against fluconazole, voriconazole, posaconazole, and Ravuconazole. Reference MIC endpoints were established after 48 h of incubation and YeastOne colorimetric endpoints were established after 24 h of incubation. YeastOne endpoints were determined to be the lowest concentration at which the color in the well changed from red (indicating growth) to purple (indicating growth inhibition) or blue (indicating no growth). Excellent agreement (within two dilutions) between the reference and colorimetric MICs was observed. Overall agreement was 95.4%. Agreement ranged from 92.3 % with posaconazole to 98.0% with fluconazole. The YeastOne colorimetric method appears to be comparable to the NCCLS reference method for testing the susceptibility of Candida spp to the new triazoles voriconazole, posaconazole, and Ravuconazole. The National Committee for Clinical Laboratory Standards (NCCLS) reference broth microdilution antifungal susceptibil-ity testing method has been established since 1997 (NCCLS M27-A) and is now used in laboratories worldwide (1, 3, 9, 17
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activities of caspofungin itraconazole posaconazole Ravuconazole voriconazole and amphotericin b against 448 recent clinical isolates of filamentous fungi
Journal of Clinical Microbiology, 2003Co-Authors: R J Hollis, Rn Jones, M A PfallerAbstract:We examined the in vitro activity of caspofungin, posaconazole, voriconazole, Ravuconazole, itraconazole, and amphotericin B against 448 recent clinical mold isolates. The endpoint for reading caspofungin was the minimum effective concentration (MEC). Among the triazoles, posaconazole was most active, inhibiting 95% of isolates at ≤1 μg/ml, followed by Ravuconazole (91%), voriconazole (90%), and itraconazole (79%). Caspofungin and amphotericin B inhibited 93% and 89% of isolates at ≤1 μg/ml, respectively, with caspofungin demonstrating an MEC 90 of 0.12 μg/ml. All three new triazoles and caspofungin inhibited >95% of Aspergillus spp. at ≤1 μg/ml compared to 83% for itraconazole and 91% for amphotericin B. Amphotericin B inhibited only 38% of Aspergillus terreus isolates at ≤1 μg/ml, whereas the three new triazoles and caspofungin inhibited all A. terreus at ≤0.5 μg/ml. The new triazoles and caspofungin have excellent in vitro activity against a very large collection of recent clinical isolates of Aspergillus spp., and some in vitro activity against selected other filamentous fungi.
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in vitro activities of Ravuconazole and voriconazole compared with those of four approved systemic antifungal agents against 6 970 clinical isolates of candida spp
Antimicrobial Agents and Chemotherapy, 2002Co-Authors: M A Pfaller, R J Hollis, Rn Jones, S A Messer, Daniel J DiekemaAbstract:The in vitro activities of Ravuconazole and voriconazole were compared with those of amphotericin B, flucytosine (5FC), itraconazole, and fluconazole against 6,970 isolates of Candida spp. obtained from over 200 medical centers worldwide. Both Ravuconazole and voriconazole were very active against all Candida spp. (MIC at which 90% of the isolates tested are inhibited [MIC90], 0.25 μg/ml; 98% of MICs were ≤1 μg/ml); however, a decrease in the activities of both of these agents was noted among isolates that were susceptible-dose dependent (fluconazole MIC, 16 to 32 μg/ml) and resistant (MIC, ≥ 64 μg/ml) to fluconazole. Candida albicans was the most susceptible species (MIC90 of both Ravuconazole and voriconazole, 0.03 μg/ml), and C. glabrata was the least susceptible species (MIC90, 1 to 2 μg/ml). Ravuconazole and voriconazole were each more active in vitro than amphotericin B, 5FC, itraconazole, and fluconazole against all Candida spp. and were the only agents with good in vitro activity against C. krusei. These results provide further evidence for the spectrum and potency of Ravuconazole and voriconazole against a large and geographically diverse collection of Candida spp.
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antifungal activities of posaconazole Ravuconazole and voriconazole compared to those of itraconazole and amphotericin b against 239 clinical isolates of aspergillus spp and other filamentous fungi report from sentry antimicrobial surveillance program 2000
Antimicrobial Agents and Chemotherapy, 2002Co-Authors: M A Pfaller, R J Hollis, S A Messer, Rn JonesAbstract:Posaconazole, Ravuconazole, and voriconazole are new triazole derivatives that possess potent, broad-spectrum antifungal activity. We evaluated the in vitro activity of these investigational triazoles compared with that of itraconazole and amphotericin B against 239 clinical isolates of filamentous fungi from the SENTRY Program, including Aspergillus spp. (198 isolates), Fusarium spp. (7 isolates), Penicillium spp. (19 isolates), Rhizopus spp. (4 isolates), Mucor spp. (2 isolates), and miscellaneous species (9 isolates). The isolates were obtained from 16 different medical centers in the United States and Canada between January and December 2000. In vitro susceptibility testing was performed using the microdilution broth method outlined in the National Committee for Clinical Laboratory Standards M38-P document. Overall, posaconazole was the most active compound, inhibiting 94% of isolates at a MIC of ≤1 μg/ml, followed by voriconazole (91%), amphotericin B (89%), Ravuconazole (88%), and itraconazole (70%). All three new triazoles demonstrated excellent activity (MIC, ≤1 μg/ml) against Aspergillus spp. (114 Aspergillus fumigatus, 22 Aspergillus niger, 13 Aspergillus flavus, 9 Aspergillus versicolor, 8 Aspergillus terreus, and 32 Aspergillus spp.): posaconazole (98%), voriconazole (98%), Ravuconazole (92%), amphotericin B (89%), and itraconazole (72%). None of the triazoles were active against Fusarium spp. (MIC at which 50% of the isolates tested were inhibited [MIC50], >8 μg/ml) or Mucor spp. (MIC50, >8 μg/ml). Posaconazole and Ravuconazole were more active than voriconazole against Rhizopus spp. (MIC50, 1 to 2 μg/ml versus >8 μg/ml, respectively). Based on these results, all three new triazoles exhibited promising activity against Aspergillus spp. and other less commonly encountered isolates of filamentous fungi. The clinical value of these in vitro data remains to be seen, and in vitro-in vivo correlation is needed for both new and established antifungal agents. Surveillance efforts should be expanded in order to monitor the spectrum of filamentous fungal pathogens and their in vitro susceptibility as these new antifungal agents are introduced into clinical use.
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international surveillance of bloodstream infections due to candida species frequency of occurrence and in vitro susceptibilities to fluconazole Ravuconazole and voriconazole of isolates collected from 1997 through 1999 in the sentry antimicrobial surveillance program
Journal of Clinical Microbiology, 2001Co-Authors: M A Pfaller, R J Hollis, Rn Jones, Daniel J Diekema, Helio S Sader, Ad C Fluit, S A MesserAbstract:A surveillance program (SENTRY) of bloodstream infections (BSI) in the United States, Canada, Latin America, and Europe from 1997 through 1999 detected 1,184 episodes of candidemia in 71 medical centers (32 in the United States, 23 in Europe, 9 in Latin America, and 7 in Canada). Overall, 55% of the yeast BSIs were due to Candida albicans, followed by Candida glabrata and Candida parapsilosis (15%), Candida tropicalis (9%), and miscellaneous Candida spp. (6%). In the United States, 45% of candidemias were due to non-C. albicans species. C. glabrata (21%) was the most common non-C. albicans species in the United States, and the proportion of non-C. albicans BSIs was highest in Latin America (55%). C. albicans accounted for 60% of BSI in Canada and 58% in Europe. C. parapsilosis was the most common non-C. albicans species in Latin America (25%), Canada (16%), and Europe (17%). Isolates of C. albicans, C. parapsilosis, and C. tropicalis were all highly susceptible to fluconazole (97 to 100% at ≤8 μg/ml). Likewise, 97 to 100% of these species were inhibited by ≤1 μg/ml of Ravuconazole (concentration at which 50% were inhibited [MIC50], 0.007 to 0.03 μg/ml) or voriconazole (MIC50, 0.007 to 0.06 μg/ml). Both Ravuconazole and voriconazole were significantly more active than fluconazole against C. glabrata (MIC90s of 0.5 to 1.0 μg/ml versus 16 to 32 μg/ml, respectively). A trend of increased susceptibility of C. glabrata to fluconazole was noted over the three-year period. The percentage of C. glabrata isolates susceptible to fluconazole increased from 48% in 1997 to 84% in 1999, and MIC50s decreased from 16 to 4 μg/ml. A similar trend was documented in both the Americas (57 to 84% susceptible) and Europe (22 to 80% susceptible). Some geographic differences in susceptibility to triazole were observed with Canadian isolates generally more susceptible than isolates from the United States and Europe. These observations suggest susceptibility patterns and trends among yeast isolates from BSI and raise additional questions that can be answered only by continued surveillance and clinical investigations of the type reported here (SENTRY Program).
Daniel J Diekema - One of the best experts on this subject based on the ideXlab platform.
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global trends in the antifungal susceptibility of cryptococcus neoformans 1990 to 2004
Journal of Clinical Microbiology, 2005Co-Authors: M A Pfaller, R J Hollis, S A Messer, Gary V Doern, L Boyken, C Rice, S Tendolkar, Daniel J DiekemaAbstract:The antifungal susceptibilities of 1,811 clinical isolates of Cryptococcus neoformans obtained from 100 laboratories in 5 geographic regions worldwide between 1990 and 2004 were determined. The MICs of amphotericin B, flucytosine, fluconazole, voriconazole, posaconazole, and Ravuconazole were determined by the National Committee for Clinical Laboratory Standards broth microdilution method. Isolates were submitted to a central reference laboratory (University of Iowa) from study centers in Africa (5 centers, 395 isolates), Europe (14 centers, 102 isolates), Latin America (14 centers, 82 isolates), the Pacific region (7 centers, 50 isolates), and North America (60 centers, 1,182 isolates). Resistance to amphotericin B, flucytosine, and fluconazole was ≤1% overall. Susceptibility to flucytosine (MIC, ≤4 μg/ml) ranged from 35% in North America to 68% in Latin America. Similarly, only 75% of isolates from North America were susceptible to fluconazole (MIC, ≤8 μg/ml) compared to 94 to 100% in the other regions. Isolates remained highly susceptible to amphotericin B (99% susceptibility at a MIC of ≤1 μg/ml) over the entire 15-year period. Susceptibility to flucytosine (MIC, ≤4 μg/ml) increased from 34% in 1990 to 1994 to 66% in 2000 to 2004. Susceptibility to fluconazole (MIC, ≤8 μg/ml) increased from 72% in 1990 to 1994 to 96% in 2000 to 2004. Voriconazole, posaconazole, and Ravuconazole all were very active (99% of isolates susceptible at MIC of ≤1 μg/ml) against this geographically diverse collection of isolates. We conclude that in vitro resistance to antifungal agents used in the treatment of cryptococcosis remains uncommon among isolates of C. neoformans from five broad geographic regions and has not increased over a 15-year period.
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Activities of Available and Investigational Antifungal Agents against Rhodotorula Species
Journal of clinical microbiology, 2005Co-Authors: Daniel J Diekema, B. Petroelje, Shawn A. Messer, Richard J. Hollis, M A PfallerAbstract:Rhodotorula species are emerging pathogens in immunocompromised patients. We report the in vitro activities of eight antifungals against 64 Rhodotorula isolates collected in surveillance programs between 1987 and 2003. Rhodotorula strains are resistant in vitro to fluconazole (MIC at which 50% of the isolates tested are inhibited [MIC(50)], >128 microg/ml) and caspofungin (MIC(50), >8 microg/ml). Amphotericin B (MIC(50),1 microg/ml) and flucytosine (MIC(50), 0.12 microg/ml) are both active in vitro, and the new and investigational triazoles all have some in vitro activity, with Ravuconazole being the most active (MIC(50), 0.25 microg/ml).
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cross resistance between fluconazole and Ravuconazole and the use of fluconazole as a surrogate marker to predict susceptibility and resistance to Ravuconazole among 12 796 clinical isolates of candida spp
Journal of Clinical Microbiology, 2004Co-Authors: M A Pfaller, R J Hollis, S A Messer, L Boyken, C Rice, S Tendolkar, Daniel J DiekemaAbstract:Cross-resistance within a class of antimicrobial agents is a problem that is often encountered with antibacterial agents, and it is also an issue with antifungal agents. A current example is Ravuconazole, a new triazole antifungal with an expanded spectrum and potency against Candida spp., Aspergillus spp., and other opportunistic fungal pathogens. The present study addresses the issue of cross-resistance between fluconazole and Ravuconazole and the use of fluconazole as a surrogate marker to predict the susceptibility of Candida spp. to Ravuconazole. Reference broth microdilution MIC results for 12,796 strains of Candida spp. isolated from more than 200 medical centers worldwide were used. Ravuconazole MICs and tentative interpretive categories (susceptible, ≤1 μg/ml; resistant, ≥2 μg/ml) were compared with those of fluconazole by using regression statistics and error rate bounding analyses. For all 12,796 isolates, the absolute categorical agreement rate was 92.5% (rate of false-susceptible results, or very major errors [VME], 0.1%). Ravuconazole was active (MIC, ≤1 μg/ml) against 99.9% of the fluconazole-susceptible isolates, 96% of the fluconazole-susceptible dose-dependent isolates, and 49% of the fluconazole-resistant isolates, including 99% of the Candida krusei isolates. Since Ravuconazole is 16- to 32-fold more potent than fluconazole, the performance of fluconazole as a surrogate marker for Ravuconazole susceptibility was improved by designating those isolates with fluconazole MICs of ≤32 μg/ml susceptible to Ravuconazole, resulting in a categorical agreement rate of 98.3%, with a VME rate of 0.3% (99 and 0.4%, respectively, when C. krusei was omitted). Cross-resistance between fluconazole and Ravuconazole applies most directly to fluconazole-resistant Candida glabrata and is variable among other species of Candida. Fluconazole may serve as a surrogate marker to predict the susceptibility of Candida spp. to Ravuconazole.
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geographic variation in the susceptibilities of invasive isolates of candida glabrata to seven systemically active antifungal agents a global assessment from the artemis antifungal surveillance program conducted in 2001 and 2002
Journal of Clinical Microbiology, 2004Co-Authors: M A Pfaller, R J Hollis, S A Messer, L Boyken, S Tendolkar, Daniel J DiekemaAbstract:We examined the susceptibilities to amphotericin B, flucytosine, fluconazole, posaconazole, Ravuconazole, voriconazole, and caspofungin of 601 invasive isolates of Candida glabrata and grouped the isolates by geographic location: North America (331 isolates), Latin America (58 isolates), Europe (135 isolates), and Asia-Pacific (77 isolates). Caspofungin (MIC at which 90% of isolates tested are susceptible [MIC(90)], 0.12 microg/ml; 100% of strains are susceptible [S] at a MIC of triazoles were most active in the Asia-Pacific region (90 to 96.1% S) and least active in North America (82.5 to 90.3% S). All 46 isolates that were resistant to fluconazole were susceptible to caspofungin (MIC(90), 0.06 microg/ml) and flucytosine (MIC(90), 0.12 microg/ml) and exhibited variable cross-resistance to posaconazole, Ravuconazole, and voriconazole.
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in vitro activities of Ravuconazole and voriconazole compared with those of four approved systemic antifungal agents against 6 970 clinical isolates of candida spp
Antimicrobial Agents and Chemotherapy, 2002Co-Authors: M A Pfaller, R J Hollis, Rn Jones, S A Messer, Daniel J DiekemaAbstract:The in vitro activities of Ravuconazole and voriconazole were compared with those of amphotericin B, flucytosine (5FC), itraconazole, and fluconazole against 6,970 isolates of Candida spp. obtained from over 200 medical centers worldwide. Both Ravuconazole and voriconazole were very active against all Candida spp. (MIC at which 90% of the isolates tested are inhibited [MIC90], 0.25 μg/ml; 98% of MICs were ≤1 μg/ml); however, a decrease in the activities of both of these agents was noted among isolates that were susceptible-dose dependent (fluconazole MIC, 16 to 32 μg/ml) and resistant (MIC, ≥ 64 μg/ml) to fluconazole. Candida albicans was the most susceptible species (MIC90 of both Ravuconazole and voriconazole, 0.03 μg/ml), and C. glabrata was the least susceptible species (MIC90, 1 to 2 μg/ml). Ravuconazole and voriconazole were each more active in vitro than amphotericin B, 5FC, itraconazole, and fluconazole against all Candida spp. and were the only agents with good in vitro activity against C. krusei. These results provide further evidence for the spectrum and potency of Ravuconazole and voriconazole against a large and geographically diverse collection of Candida spp.
