scholarly journals In Vitro Activities of Posaconazole (Sch 56592) Compared with Those of Itraconazole and Fluconazole against 3,685 Clinical Isolates of Candida spp. andCryptococcus neoformans

2001 ◽  
Vol 45 (10) ◽  
pp. 2862-2864 ◽  
Author(s):  
M. A. Pfaller ◽  
S. A. Messer ◽  
R. J. Hollis ◽  
R. N. Jones
Keyword(s):  
Candida Glabrata ◽  
Fungal Pathogens ◽  
Clinical Laboratory ◽  
Antifungal Drugs ◽  
National Committee ◽  
Broth Microdilution ◽  
Test Medium ◽  
Candida Spp ◽  
Medical Centers

ABSTRACT Posaconazole is a new investigational triazole with broad-spectrum antifungal activity. The in vitro activities of posaconazole were compared with those of itraconazole and fluconazole against 3,685 isolates of Candida spp. (3,312 isolates) and C. neoformans (373 isolates) obtained from over 70 different medical centers worldwide. The MICs of the antifungal drugs were determined by broth microdilution tests performed according to the National Committee for Clinical Laboratory Standards method using RPMI 1640 as the test medium. Posaconazole was very active against all Candida spp. (MIC at which 90% of the isolates were inhibited [MIC90], 0.5 μg/ml; 97% of MICs were ≤1 μg/ml) and C. neoformans(MIC90, 0.5 μg/ml; 100% of MICs were ≤1 μg/ml).Candida albicans was the most susceptible species ofCandida (MIC90, 0.06 μg/ml), andCandida glabrata was the least susceptible (MIC90, 4 μg/ml). Posaconazole was more active than itraconazole and fluconazole against all Candida spp. and C. neoformans. These results provide further evidence for the spectrum and potency of posaconazole against a large and geographically diverse collection of clinically important fungal pathogens.

scholarly journals In Vitro Susceptibilities of CandidaBloodstream Isolates to the New Triazole Antifungal Agents BMS-207147, Sch 56592, and Voriconazole

1998 ◽  
Vol 42 (12) ◽  
pp. 3242-3244 ◽  
Author(s):  
M. A. Pfaller ◽  
S. A. Messer ◽  
R. J. Hollis ◽  
R. N. Jones ◽  
G. V. Doern ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Clinical Laboratory ◽  
Rank Order ◽  
The United States ◽  
Antifungal Drugs ◽  
National Committee ◽  
Clinical Value ◽  
Medical Centers

ABSTRACT BMS-207147, Sch 56592, and voriconazole are three new investigational triazoles with broad-spectrum antifungal activity. The in vitro activities of these three agents were compared with those of itraconazole and fluconazole against 1,300 bloodstream isolates ofCandida species obtained from over 50 different medical centers in the United States. The MICs of all of the antifungal drugs were determined by broth microdilution tests performed according to the National Committee for Clinical Laboratory Standards method using RPMI 1640 as a test medium. BMS-207147, Sch 56592, and voriconazole were all quite active against all Candida sp. isolates (MICs for 90% of the isolates tested [MIC90s], 0.5, 1.0, and 0.5 μg/ml, respectively). Candida albicans was the most susceptible species (MIC90s, 0.03, 0.06, and 0.06 μg/ml, respectively), and C. glabrata was the least susceptible (MIC90s, 4.0, 4.0, and 2.0 μg/ml, respectively). BMS-207147, Sch 56592, and voriconazole were all more active than itraconazole and fluconazole against C. albicans, C. parapsilosis, C. tropicalis, and C. krusei. There existed a clear rank order of in vitro activity of the five azoles examined in this study when they were tested versusC. glabrata: voriconazole > BMS-207147 = Sch 56592 = itraconazole > fluconazole (MIC90s, 2.0, 4.0, 4.0, 4.0, and 64 μg/ml, respectively). For isolates ofCandida spp. with decreased susceptibility to both itraconazole and fluconazole, the MICs of BMS-207147, Sch 56592, and voriconazole were also elevated. These results suggest that BMS-207147, Sch 56592, and voriconazole all possess promising antifungal activity and that further in vitro and in vivo investigations are warranted to establish the clinical value of this improved potency.

In Vitro Activities of Voriconazole (UK-109,496) and Four Other Antifungal Agents against 394 Clinical Isolates ofCandida spp.

1998 ◽  
Vol 42 (1) ◽  
pp. 161-163 ◽  
Author(s):  
F. Marco ◽  
M. A. Pfaller ◽  
S. Messer ◽  
R. N. Jones
Keyword(s):  
Amphotericin B ◽  
Antifungal Agents ◽  
Clinical Laboratory ◽  
Candida Krusei ◽  
Antifungal Drugs ◽  
National Committee ◽  
In Vitro Activity ◽  
Medical Centers

ABSTRACT Voriconazole (formerly UK-109,496) is a new monotriazole antifungal agent which has potent activity against Candida,Cryptococcus, and Aspergillus species. We investigated the in vitro activity of voriconazole compared to those of fluconazole, itraconazole, amphotericin B, and flucytosine (5FC) against 394 bloodstream isolates of Candida (five species) obtained from more than 30 different medical centers. MICs of all antifungal drugs were determined by the method recommended by the National Committee for Clinical Laboratory Standards using RPMI 1640 test medium. Overall, voriconazole was quite active against all the yeast isolates (MIC at which 90% of the isolates are inhibited [MIC90], ≤0.5 μg/ml). Candida albicans was the most susceptible species (MIC90, 0.06 μg/ml) andCandida glabrata and Candida krusei were the least (MIC90, 1 μg/ml). Voriconazole was more active than amphotericin B and 5FC against all species except C. glabrata and was also more active than itraconazole and fluconazole. For isolates of Candida spp. with decreased susceptibility to fluconazole and itraconazole MICs of voriconazole were also higher. Based on these results, voriconazole has promising antifungal activity and further in vitro and in vivo investigations are warranted.

scholarly journals In Vitro Activities of 5-Fluorocytosine against 8,803 Clinical Isolates of Candida spp.: Global Assessment of Primary Resistance Using National Committee for Clinical Laboratory Standards Susceptibility Testing Methods

2002 ◽  
Vol 46 (11) ◽  
pp. 3518-3521 ◽  
Author(s):  
M. A. Pfaller ◽  
S. A. Messer ◽  
L. Boyken ◽  
H. Huynh ◽  
R. J. Hollis ◽  
...  
Keyword(s):  
Clinical Laboratory ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
National Committee ◽  
In Vitro Activity ◽  
Candida Spp ◽  
Primary Resistance ◽  
Antifungal Effect ◽  
Medical Centers

ABSTRACT We determined the in vitro activity of flucytosine (5-fluorocytosine [5FC]) against 8,803 clinical isolates of Candida spp. (18 species) obtained from more than 200 medical centers worldwide between 1992 and 2001. The MICs were determined by broth microdilution tests performed according to NCCLS guidelines by using RPMI 1640 as the test medium and the following interpretive breakpoints: susceptible (S), ≤4 μg/ml; intermediate (I), 8 to 16 μg/ml; resistant (R), ≥32 μg/ml. 5FC was very active against the 8,803 Candida isolates (MIC90, 1 μg/ml), 95% S. A total of 99 to 100% of C. glabrata (MIC90, 0.12 μg/ml), C. parapsilosis (MIC90, 0.25 μg/ml), C. dubliniensis (MIC90, 0.12 μg/ml), C. guilliermondii (MIC90, 0.5 μg/ml), and C. kefyr (MIC90, 1 μg/ml) were susceptible to 5FC at the NCCLS breakpoint. C. albicans (MIC90, 1 μg/ml; 97% S) and C. tropicalis (MIC90, 1 μg/ml; 92% S) were only slightly less susceptible. In contrast, C. krusei was the least susceptible species: 5% S; MIC90, 32 μg/ml. Primary resistance to 5FC is very uncommon among Candida spp. (95% S, 2% I, and 3% R), with the exception of C. krusei (5% S, 67% I, and 28% R). The in vitro activity of 5FC, combined with previous data demonstrating a prolonged post-antifungal effect (2.5 to 4 h) and concentration-independent activity (optimized at 4× MIC), suggest that 5FC could be used in lower doses to reduce host toxicity while maintaining antifungal efficacy.

scholarly journals In Vitro Activities of Caspofungin Compared with Those of Fluconazole and Itraconazole against 3,959 Clinical Isolates of Candida spp., Including 157 Fluconazole-Resistant Isolates

2003 ◽  
Vol 47 (3) ◽  
pp. 1068-1071 ◽  
Author(s):  
M. A. Pfaller ◽  
D. J. Diekema ◽  
S. A. Messer ◽  
R. J. Hollis ◽  
R. N. Jones
Keyword(s):  
Antifungal Drugs ◽  
Broth Microdilution ◽  
Candida Spp ◽  
Medical Centers ◽  
Spectrum Activity ◽  
Fluconazole Resistant ◽  
High Level ◽  
Level Resistance ◽  
Broad Spectrum Activity

ABSTRACT Caspofungin is an echinocandin antifungal agent with broad-spectrum activity against Candida and Aspergillus spp. The in vitro activities of caspofungin against 3,959 isolates of Candida spp. obtained from over 95 different medical centers worldwide were compared with those of fluconazole and itraconazole. The MICs of the antifungal drugs were determined by broth microdilution tests performed according to the NCCLS method using RPMI 1640 as the test medium. Caspofungin was very active against Candida spp. (MIC at which 90% of the isolates were inhibited [MIC90], 1 μg/ml; 96% of MICs were ≤2 μg/ml). Candida albicans, C. dubliniensis, C. tropicalis, and C. glabrata were the most susceptible species of Candida (MIC90, 0.25 to 0.5 μg/ml), and C. guilliermondii was the least susceptible (MIC90, >8 μg/ml). Caspofungin was very active against Candida spp., exhibiting high-level resistance to fluconazole and itraconazole (99% of MICs were ≤1 μg/ml). These results provide further evidence for the spectrum and potency of caspofungin activity against a large and geographically diverse collection of clinically important isolates of Candida spp.

scholarly journals In Vitro Activities of the New Antifungal Triazole SCH 56592 against Common and Emerging Yeast Pathogens

2000 ◽  
Vol 44 (1) ◽  
pp. 226-229 ◽  
Author(s):  
Francesco Barchiesi ◽  
Daniela Arzeni ◽  
Annette W. Fothergill ◽  
Luigi Falconi Di Francesco ◽  
Francesca Caselli ◽  
...  
Keyword(s):  
Clinical Laboratory ◽  
Clinical Development ◽  
National Committee ◽  
In Vitro Activity ◽  
Broth Microdilution ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Vitro Data ◽  
In Vitro Data

ABSTRACT A broth microdilution method performed in accordance with the National Committee for Clinical Laboratory Standards guidelines was used to compare the in vitro activity of the new antifungal triazole SCH 56592 (SCH) to that of fluconazole (FLC), itraconazole (ITC), and ketoconazole (KETO) against 257 clinical yeast isolates. They included 220 isolates belonging to 12 different species of Candida, 15 isolates each of Cryptococcus neoformans andSaccharomyces cerevisiae, and seven isolates ofRhodotorula rubra. The MICs of SCH at which 50% (MIC50) and 90% (MIC90) of the isolates were inhibited were 0.06 and 2.0 μg/ml, respectively. In general, SCH was considerably more active than FLC (MIC50 and MIC90 of 1.0 and 64 μg/ml, respectively) and slightly more active than either ITC (MIC50 and MIC90 of 0.25 and 2.0 μg/ml, respectively) and KETO (MIC50 and MIC90 of 0.125 and 4.0 μg/ml, respectively). Our in vitro data suggest that SCH has significant potential for clinical development.

scholarly journals Comparison of NCCLS and 3-(4,5-Dimethyl-2-Thiazyl)-2,5-Diphenyl-2H-Tetrazolium Bromide (MTT) Methods of In Vitro Susceptibility Testing of Filamentous Fungi and Development of a New Simplified Method

2000 ◽  
Vol 38 (8) ◽  
pp. 2949-2954 ◽  
Author(s):  
Joseph Meletiadis ◽  
Jacques F. G. M. Meis ◽  
Johan W. Mouton ◽  
J. Peter Donnelly ◽  
Paul E. Verweij
Keyword(s):  
Filamentous Fungi ◽  
Clinical Laboratory ◽  
Colorimetric Method ◽  
Antifungal Drugs ◽  
National Committee ◽  
In Vitro Susceptibility ◽  
Initial Inoculum ◽  
Tetrazolium Bromide ◽  
Mtt Method

The susceptibility of 30 clinical isolates belonging to six different species of filamentous fungi (Aspergillus fumigatus, Aspergillus flavus, Scedosporium prolificans, Scedosporium apiospermum, Fusarium solani, and Fusarium oxysporum) was tested against six antifungal drugs (miconazole, voriconazole, itraconazole, UR9825, terbinafine, and amphotericin B) with the microdilution method recommended by the National Committee for Clinical Laboratory Standards (NCCLS) (M38-P). The MICs were compared with the MICs obtained by a colorimetric method measuring the reduction of the dye 3-(4,5-dimethyl-2-thiazyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) to formazan by viable fungi. The levels of agreement between the two methods were 96 and 92% for MIC-0 (clear wells) and MIC-1 (75% growth reduction), respectively. The levels of agreement were always higher for Aspergillus spp. (97% ± 2.5%), followed byScedosporium spp. (87% ± 10.3%) and Fusariumspp. (78% ± 7.8%). The NCCLS method was more reproducible than the MTT method: 98 versus 95% for MIC-0 and 97 versus 90% for MIC-1. However, the percentage of hyphal growth as determined visually by the NCCLS method showed several discrepancies when they were compared with the percentages of MTT reduction. A new simplified assay that incorporates the dye MTT with the initial inoculum and in which the fungi are incubated with the dye for 48 h or more was developed, showing comparable levels of agreement and reproducibility with the other two methods. Furthermore, the new assay was easier to perform and more sensitive than the MTT method.

scholarly journals Evaluation of Amphotericin B Interpretive Breakpoints for Candida Bloodstream Isolates by Correlation with Therapeutic Outcome

2006 ◽  
Vol 50 (4) ◽  
pp. 1287-1292 ◽  
Author(s):  
Benjamin J. Park ◽  
Beth A. Arthington-Skaggs ◽  
Rana A. Hajjeh ◽  
Naureen Iqbal ◽  
Meral A. Ciblak ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Susceptibility Testing ◽  
Clinical Laboratory ◽  
National Committee ◽  
Restricted Range ◽  
Broth Microdilution ◽  
Therapeutic Success ◽  
In Vitro Susceptibility ◽  
In Vitro Susceptibility Testing

ABSTRACT One hundred seven Candida bloodstream isolates (51 C. albicans, 24 C. glabrata, 13 C. parapsilosis, 13 C. tropicalis, 2 C. dubliniensis, 2 C. krusei, and 2 C. lusitaniae strains) from patients treated with amphotericin B alone underwent in vitro susceptibility testing against amphotericin B using five different methods. Fifty-four isolates were from patients who failed treatment, defined as death 7 to 14 days after the incident candidemia episode, having persistent fever of ≥5 days' duration after the date of the incident candidemia, or the recurrence of fever after two consecutive afebrile days while on antifungal treatment. MICs were determined by using the Clinical Laboratory Standards Institute (formally National Committee for Clinical Laboratory Standards) broth microdilution procedure with two media and by using Etest. Minimum fungicidal concentrations (MFCs) were also measured in two media. Broth microdilution tests with RPMI 1640 medium generated a restricted range of MICs (0.125 to 1 μg/ml); the corresponding MFC values ranged from 0.5 to 4 μg/ml. Broth microdilution tests with antibiotic medium 3 produced a broader distribution of MIC and MFC results (0.015 to 0.25 μg/ml and 0.06 to 2 μg/ml, respectively). Etest produced the widest distribution of MICs (0.094 to 2 μg/ml). However, none of the test formats studied generated results that significantly correlated with therapeutic success or failure.

scholarly journals In Vitro Activity of the New Triazole Voriconazole (UK-109,496) against Opportunistic Filamentous and Dimorphic Fungi and Common and Emerging Yeast Pathogens

1998 ◽  
Vol 36 (1) ◽  
pp. 198-202 ◽  
Author(s):  
Ana Espinel-Ingroff
Keyword(s):  
Amphotericin B ◽  
Clinical Laboratory ◽  
Wide Spectrum ◽  
Sporothrix Schenckii ◽  
National Committee ◽  
Broth Microdilution ◽  
Pseudallescheria Boydii ◽  
Broth Microdilution Method ◽  
Better Than

The in vitro antifungal activity of a new triazole derivative, voriconazole, was compared with those of itraconazole and amphotericin B against 67 isolates of Aspergillus flavus,Aspergillus fumigatus, Bipolaris spp.,Fusarium oxysporum, Fusarium solani,Pseudallescheria boydii, Rhizopus arrhizus,Blastomyces dermatitidis, Histoplasma capsulatum, and Sporothrix schenckii. The in vitro activities of voriconazole were also compared with those of amphotericin B, fluconazole, and itraconazole against 189 isolates of emerging and common yeast pathogens of Blastoschizomyces capitatus, Candida (13 species), Cryptococcus neoformans, Hansenula anomala, Rhodotorula rubra, Saccharomyces cerevisiae, Sporobolomyces salmonicolor, and Trichosporon beigelii. MICs were determined according to a procedure under evaluation by the National Committee for Clinical Laboratory Standards (NCCLS) for broth microdilution testing of filamentous fungi and by the NCCLS M27-A broth microdilution method for yeasts. The in vitro activities of voriconazole were similar to or better than those of itraconazole and amphotericin B against Aspergillus spp.,Fusarium spp., and P. boydii as well as againstB. dermatitidis and H. capsulatum. The activities of voriconazole were also comparable to or better than those of amphotericin B, fluconazole, and itraconazole against most species of yeasts tested. Exceptions were certain isolates of R. rubra and S. salmonicolor. These results suggest that voriconazole has a wide spectrum of activity in vitro; its effectiveness in the treatment of human mycoses is under evaluation in clinical trials.

In vitro studies of activities of the antifungal triazoles SCH56592 and itraconazole against Candida albicans, Cryptococcus neoformans, and other pathogenic yeasts.

1997 ◽  
Vol 41 (1) ◽  
pp. 180-183 ◽  
Author(s):  
J N Galgiani ◽  
M L Lewis
Keyword(s):  
Incubation Temperature ◽  
Clinical Laboratory ◽  
Synthetic Medium ◽  
Reference Method ◽  
Inoculum Size ◽  
Antifungal Drugs ◽  
Yeast Cells ◽  
National Committee ◽  
Broth Macrodilution

We investigated the effects of various assay conditions on the activities of two antifungal drugs, SCH56592 and itraconazole, against seven species of fungi by the broth macrodilution testing procedure proposed by the National Committee for Clinical Laboratory Standards (NCCLS). For both drugs, which are insoluble in water, the concentration and type of solubilizing agent produced differences in drug activity. Starting inoculum size differences from 10(2) to 10(5) yeast cells per ml resulted in approximately a fourfold effect on the MIC of both drugs, but other significant differences were not observed with variations in synthetic medium composition, pH, buffering reagent, or incubation temperature. Under standardized conditions of reference method M27-T with 1% polyethylene glycol as the solubilizing agent, median MICs of SCH56592 and itraconazole of 60 and 125 mg/ml, respectively, were demonstrated for 110 strains (12 to 23 strains for each of seven species). Broth microdilution results were typically severalfold higher than broth macrodilution results. We conclude that the NCCLS standard reference method can be applied without modification to the testing of SCH56592 and itraconazole, but particular attention to solubilizing the agents is critical to obtaining consistent results.

scholarly journals In Vitro Susceptibility Tests for Cationic Peptides: Comparison of Broth Microdilution Methods for Bacteria That Grow Aerobically

2000 ◽  
Vol 44 (6) ◽  
pp. 1694-1696 ◽  
Author(s):  
A. Giacometti ◽  
O. Cirioni ◽  
F. Barchiesi ◽  
M. S. Del Prete ◽  
M. Fortuna ◽  
...  
Keyword(s):  
Clinical Laboratory ◽  
Aerobic Bacteria ◽  
National Committee ◽  
Cationic Peptides ◽  
Broth Microdilution ◽  
In Vitro Susceptibility ◽  
Cecropin P1 ◽  
Magainin Ii ◽  
Susceptibility Tests

ABSTRACT The in vitro susceptibilities of 90 clinical isolates of gram-positive and gram-negative aerobic bacteria to six cationic peptides, buforin II, cecropin P1, indolicidin, magainin II, nisin, and ranalexin, were evaluated by two broth microdilution methods. The first method was performed according to the procedures outlined by the National Committee for Clinical Laboratory Standards for bacteria that grow aerobically, while the second was performed according to the procedures recently proposed by the R. E. W. Hancock laboratory for testing antimicrobial peptides. Overall, the first method produced MICs two- and fourfold higher than the second method.

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