Head-to-head comparison of the activities of currently available antifungal agents against 3,378 Spanish clinical isolates of yeasts and filamentous fungi

We have compared the activities of posaconazole and other currently available antifungal agents against a collection of 3,378 clinical isolates of yeasts and filamentous fungi. A total of 1,997 clinical isolates of Candida spp., 359 of other yeast species, 697 strains of Aspergillus spp., and 325 nondermatophyte non-Aspergillus spp. were included. The average geometric means of the MICs of agents that were tested against Candida spp. were 0.23 microg/ml for amphotericin B, 0.29 microg/ml for flucytosine, 0.97 microg/ml for fluconazole, 0.07 microg/ml for itraconazole, 0.04 microg/ml for voriconazole, 0.15 microg/ml for caspofungin, and 0.03 microg/ml for posaconazole. Voriconazole and posaconazole were active in vitro against the majority of isolates, with resistance to fluconazole and itraconazole, and against Cryptococcus neoformans and other Basidiomycota yeasts. Posaconazole was the most active of antifungal agents tested against Aspergillus spp., with an average geometric mean of 0.10 microg/ml. It was active against Paecilomyces spp., Penicillium spp., Scedosporium apiospermum, and some black fungi, such as Alternaria spp. Multiresistant filamentous fungi, such as Scedosporium prolificans, Scopulariopsis brevicaulis, and Fusarium solani, were also resistant to voriconazole, caspofungin, and posaconazole. Amphotericin B and posaconazole were found to be active against most of the Mucorales strains tested. Posaconazole and currently available antifungal agents exhibit a potent activity in vitro against the majority of pathogenic fungal species.     

Activities of E1210 and comparator agents tested by CLSI and EUCAST broth microdilution methods against Fusarium and Scedosporium species identified using molecular methods

Fusarium (n = 67) and Scedosporium (n = 63) clinical isolates were tested by two reference broth microdilution (BMD) methods against a novel broad-spectrum (active against both yeasts and molds) antifungal, E1210, and comparator agents. E1210 inhibits the inositol acylation step in glycophosphatidylinositol (GPI) biosynthesis, resulting in defects in fungal cell wall biosynthesis. Five species complex organisms/species of Fusarium (4 isolates unspeciated) and 28 Scedosporium apiospermum, 7 Scedosporium aurantiacum, and 28 Scedosporium prolificans species were identified by molecular techniques. Comparator antifungal agents included anidulafungin, caspofungin, itraconazole, posaconazole, voriconazole, and amphotericin B. E1210 was highly active against all of the tested isolates, with minimum effective concentration (MEC)/MIC(90) values (μg/ml) for E1210, anidulafungin, caspofungin, itraconazole, posaconazole, voriconazole, and amphotericin B, respectively, for Fusarium of 0.12, >16, >16, >8, >8, 8, and 4 μg/ml. E1210 was very potent against the Scedosporium spp. tested. The E1210 MEC(90) was 0.12 μg/ml for S. apiospermum, but 1 to >8 μg/ml for other tested agents. Against S. aurantiacum, the MEC(50) for E1210 was 0.06 μg/ml versus 0.5 to >8 μg/ml for the comparators. Against S. prolificans, the MEC(90) for E1210 was only 0.12 μg/ml, compared to >4 μg/ml for amphotericin B and >8 μg/ml for itraconazole, posaconazole, and voriconazole. Both CLSI and EUCAST methods were highly concordant for E1210 and all comparator agents. The essential agreement (EA; ±2 doubling dilutions) was >93% for all comparisons, with the exception of posaconazole and F. oxysporum species complex (SC) (60%), posaconazole and S. aurantiacum (85.7%), and voriconazole and S. aurantiacum (85.7%). In conclusion, E1210 exhibited very potent and broad-spectrum antifungal activity against azole- and amphotericin B-resistant strains of Fusarium spp. and Scedosporium spp. Furthermore, in vitro susceptibility testing of E1210 against isolates of Fusarium and Scedosporium may be accomplished using either of the CLSI or EUCAST BMD methods, each producing very similar results.     

Antifungal activity of posaconazole compared with fluconazole and amphotericin B against yeasts from oropharyngeal candidiasis and other infections

OBJECTIVES: The in vitro antifungal activity of posaconazole was compared with that of fluconazole and amphotericin B. Materials and methods: A microdilution method (M27-A2) was used with 331 clinical yeast isolates. RESULTS: The geometric mean MICs of posaconazole, fluconazole and amphotericin B were 0.16, 0.91 and 0.15 mg/L, respectively. Posaconazole was markedly more active than fluconazole and was active against 9/11 fluconazole-resistant Candida albicans, and five Candida glabrata had an MIC of posaconazole of 16 mg/L. CONCLUSIONS: These data indicate that posaconazole is a potentially effective antifungal agent for the treatment of mycoses caused by yeasts.     

Susceptibility testing of voriconazole, fluconazole, itraconazole and amphotericin B against yeast isolates in a Turkish University Hospital and effect of time of reading

Voriconazole is a promising azole effective against a variety of fungi, including yeasts. In this study, we tested in vitro activities of voriconazole, fluconazole, itraconazole and amphotericin B against some ATCC and reference strains and 250 clinical yeast isolates. We also evaluated the effect of time of reading on MIC results. Voriconazole was the most active agent against Candida and Trichosporon isolates, including the putatively fluconazole-resistant C. krusei (MIC(90) 0.25 microg/ml) and C. glabrata (MIC(90) 0.5 microg/ml). Amphotericin B MICs were scattered in a considerably narrow range in both RPMI 1640 and Antibiotic Medium 3. MICs at 24 hours and 48 hours were similar in general for all antifungals tested. The highest percentage of strains that showed 24-hour and 48-hour MICs within +/-1-log(2) dilution was observed for amphotericin B tested in RPMI (99%), and the lowest for amphotericin B tested in Antibiotic Medium 3 (80%). In conclusion, voriconazole is very effective against a wide spectrum of Candida species and 24-hour readings could substitute 48-hour MIC evaluation.     

In vitro activities of posaconazole (Sch 56592) compared with those of itraconazole and fluconazole against 3,685 clinical isolates of Candida spp. and Cryptococcus neoformans

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 [MIC(90)], 0.5 microg/ml; 97% of MICs were < or =1 microg/ml) and C. neoformans (MIC(90), 0.5 microg/ml; 100% of MICs were < or =1 microg/ml). Candida albicans was the most susceptible species of Candida (MIC(90), 0.06 microg/ml), and Candida glabrata was the least susceptible (MIC(90), 4 microg/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.     

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

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 < or = 1 microg/ml, followed by voriconazole (91%), amphotericin B (89%), ravuconazole (88%), and itraconazole (70%). All three new triazoles demonstrated excellent activity (MIC, < or = 1 microg/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 [MIC(50)], >8 microg/ml) or Mucor spp. (MIC(50), >8 microg/ml). Posaconazole and ravuconazole were more active than voriconazole against Rhizopus spp. (MIC(50), 1 to 2 microg/ml versus >8 microg/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.     

In vitro activities of ravuconazole and voriconazole compared with those of four approved systemic antifungal agents against 6,970 clinical isolates of Candida spp

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 [MIC(90)], 0.25 microg/ml; 98% of MICs were < or 1 microg/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 microg/ml) and resistant (MIC, > or = 64 microg/ml) to fluconazole. Candida albicans was the most susceptible species (MIC(90) of both ravuconazole and voriconazole, 0.03 microg/ml), and C. glabrata was the least susceptible species (MIC(90), 1 to 2 microg/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.     

Azole Cross-Resistance in Aspergillus fumigatus

We susceptibility tested 17 clinical isolates of Aspergillus fumigatus, for most of which MICs of itraconazole were elevated (MIC at which 50% of the isolates tested are inhibited, 16 microg/ml), against itraconazole, posaconazole, ravuconazole, and voriconazole. Posaconazole was the most active against itraconazole-susceptible isolates. A complex pattern of cross-resistance and hypersusceptibility was seen with voriconazole and ravuconazole, suggesting marked differences in activity and mechanisms of resistance.     

In Vitro activity of the new azole isavuconazole (BAL4815) compared with six other antifungal agents against 162 Cryptococcus neoformans isolates from Cuba

Cuban Cryptococcus isolates (n = 165) were tested in vitro against amphotericin B, flucytosine, fluconazole, itraconazole, voriconazole, posaconazole, and isavuconazole, giving MIC90 values of 0.25, 8, 4, 0.25, 0.125, 0.016, and 0.016 microg/ml, respectively. Isavuconazole and posaconazole seem to be potentially active drugs for treating cryptococcal infections.     

In vitro evaluation of voriconazole against some clinically important fungi.

Voriconazole was compared to amphotericin B, fluconazole, and itraconazole by using an in vitro macrobroth dilution test based upon current National Committee for Clinical Laboratory Standards tentative standards against the dimorphic fungi and several opportunistic molds and yeasts. In all instances, the voriconazole MICs were lower than those of fluconazole. In most instances, the MICs were lower than the recorded MICs of amphotericin B and itraconazole.     

In vitro activities of posaconazole, itraconazole, voriconazole, amphotericin B, and fluconazole against 37 clinical isolates of zygomycetes

In vitro antifungal susceptibility testing results of a new antifungal triazole, posaconazole (POS), were compared to results with amphotericin B (AMB), itraconazole (ITC), voriconazole (VRC), and fluconazole (FLC) against clinical agents of zygomycosis. The MICs of POS at which 50% and 90% of the isolates were inhibited were 0.25 and 4 microg/ml, respectively. POS was significantly more active than VRC and FLC and slightly more active than ITC. The results suggest that POS has significant potential for clinical development against the zygomycetes.     

In vitro and in vivo antifungal activities of ER-30346, a novel oral triazole with a broad antifungal spectrum.

ER-30346 is a novel oral triazole with a broad spectrum of potent activity against a wide range of fungi. ER-30346, with MICs at which 90% of the strains tested are inhibited (MIC90s) ranging from 0.025 to 0.78 microgram/ml, was 4 to 32 times more active than itraconazole, fluconazole, and amphotericin B against Candida albicans, Candida parapsilosis, and Candida glabrata. Against Candida tropicalis, ER-30346, with an MIC90 of 12.5 micrograms/ml, was 2 to > 8 times more active than itraconazole and fluconazole, but was 16 times less active than amphotericin B. ER-30346 (MIC90, 0.78 microgram/ml) was four to eight times more active than fluconazole and amphotericin B and had activity comparable to that of itraconazole against Trichosporon beigelli. The MIC90s of ER-30346 were 0.10 microgram/ml for Cryptococcus neoformans and 0.39 microgram/ml for Aspergillus fumigatus. ER-30346 was 2 to 8 times more active than itraconazole and amphotericin B and 32 to > 256 times more active than fluconazole. ER-30346 also showed good activity against dermatophytes, with MICs ranging from 0.05 to 0.39 microgram/ml, and its activity was comparable to or 2 to 16 times higher than those of itraconazole and amphotericin B and > 32 times higher than that of fluconazole. In vivo activity was evaluated with systemic infections in mice. Against systemic candidiasis and cryptococcosis, ER-30346 was comparable in efficacy to fluconazole and was more effective than itraconazole. Of the drugs tested, ER-30346 was the most effective drug against systemic aspergillosis. We studied the levels of ER-30346 in mouse plasma. The maximum concentration of drug in plasma and the area under the concentration-time curve for ER-30346 showed good linearity over a range of doses from 2 to 40 mg/kg of body weight.     

Antifungal susceptibilities of clinical isolates of Candida species, Cryptococcus neoformans, and Aspergillus species from Taiwan: surveillance of multicenter antimicrobial resistance in Taiwan program data from 2003

The susceptibilities of nonduplicate isolates to six antifungal agents were determined for 391 blood isolates of seven Candida species, 70 clinical isolates (from blood or cerebrospinal fluid) of Cryptococcus neoformans, and 96 clinical isolates of four Aspergillus species, which were collected in seven different hospitals in Taiwan (as part of the 2003 program of the study group Surveillance of Multicenter Antimicrobial Resistance in Taiwan). All isolates of Candida species other than C. glabrata and C. krusei were susceptible to fluconazole. Among the 59 C. glabrata isolates, 16 (27%) were not susceptible to fluconazole, and all were dose-dependently susceptible or resistant to itraconazole. For three (5.1%) C. glabrata isolates, voriconazole MICs were 2 to 4 microg/ml, and for all other Candida species isolates, voriconazole MICs were /=2 microg/ml were 100% (3 isolates) for C. krusei, 11% (23 of 207 isolates) for Candida albicans, 3.0% (2 of 67 isolates) for Candida tropicalis, 20% (12 of 59 isolates) for C. glabrata, and 0% for both Candida parapsilosis and Candida lusitaniae. For three (4%) Cryptococcus neoformans isolates, fluconazole MICs were >/=16 microg/ml, and two (3%) isolates were not inhibited by 1 mug of amphotericin B/ml. For four (4.2%) of the Aspergillus isolates, itraconazole MICs were 8 microg/ml. Aspergillus flavus was less susceptible to amphotericin B, with the MICs at which 50% (1 microg/ml) and 90% (2 microg/ml) nsrsid417869\delrsid7301351 of isolates were inhibited being twofold greater than those for Aspergillus fumigatus and Aspergillus niger. All Aspergillus isolates were inhibited by 相似文献   

In vitro activity of three new triazoles and one echinocandin against Candida bloodstream isolates from cancer patients

The in vitro activities of voriconazole, posaconazole, ravuconazole and micafungin were compared with those of fluconazole, itraconazole, ketoconazole, flucytosine and amphotericin B against 164 candidaemia isolates recovered from cancer patients in two Canadian centres. The MIC(50) results for ravuconazole, voriconazole, posaconazole and micafungin were 0.01, 0.03, 0.12 and 0.25 mg/L, respectively. The new antifungal agents showed substantial activity against isolates demonstrating in vitro resistance to fluconazole and itraconazole. These results suggest that the newer antifungal agents possess promising activity against invasive Candida isolates, particularly against those with reduced susceptibility to fluconazole and itraconazole.     

In vitro activities of new and conventional antifungal agents against clinical Scedosporium isolates.

The susceptibilities of 13 clinical isolates of Scedosporium apiospermum and 55 clinical isolates of S. prolificans to new and conventional drugs belonging to three different classes of antifungal agents, the azoles (miconazole, itraconazole, voriconazole, UR-9825, posaconazole), the polyenes (amphotericin B, nystatin and liposomal nystatin), and allylamines (terbinafine), were studied by use of proposed standard M38-P of NCCLS. Low growth-inhibitory antifungal activities were found in vitro for most of the drugs tested against S. prolificans isolates, with the MICs at which 90% of isolates are inhibited (MIC(90)s) being >8 microg/ml; the MIC(90)s of voriconazole and UR-9825, however, were 4 microg/ml. S. apiospermum isolates were more susceptible in vitro, with the highest activity exhibited by voriconazole (MIC(90)s, 0.5 microg/ml), followed by miconazole (MIC(90)s, 1 microg/ml), UR-9825 and posaconazole (MIC(90)s, 2 microg/ml), and itraconazole (MIC(90)s, 4 microg/ml). The MICs of terbinafine, amphotericin B, and the two formulations of nystatin (for which no statistically significant differences in antifungal activities were found for the two species) for S. apiospermum isolates were high. Cross-resistance was observed among all the azoles except posaconazole and among all the polyenes except the lipid formulation. A distribution analysis was performed with the MICs of each drug and for each species. Bimodal and skewed MIC distributions were obtained, and cutoffs indicating the borders of different MIC subpopulations of the distributions were determined on the basis of the normal plot technique. These cutoffs were in many cases reproducible between 48 and 72 h.     

In vitro antifungal susceptibilities of Trichosporon species

The in vitro activities of amphotericin B, itraconazole, fluconazole, voriconazole, posaconazole, and ravuconazole against 39 isolates of Trichosporon spp. were determined by the NCCLS M27-A microdilution method. The azoles tested appeared to be more potent than amphotericin B. Low minimal fungicidal concentration/MIC ratios were observed for voriconazole, posaconazole, and ravuconazole, suggesting fungicidal activity.     

In vitro activities of voriconazole, itraconazole, and amphotericin B against Blastomyces dermatitidis, Coccidioides immitis, and Histoplasma capsulatum

The in vitro activity of voriconazole was compared to those of itraconazole and amphotericin B against the mold forms of 304 isolates of three dimorphic fungi, Blastomyces dermatitidis, Coccidioides immitis, and Histoplasma capsulatum. MICs were determined by a broth microdilution adaptation of the National Committee for Clinical Laboratory Standards M27-A procedure. RPMI 1640 medium was used for tests with voriconazole and itraconazole, whereas Antibiotic Medium 3 with 2% glucose was used for amphotericin B. Minimum fungicidal concentrations (MFCs) were also determined. Amphotericin B was active against all three dimorphic fungi, with MICs at which 90% of the isolates tested are inhibited (MIC(90)s) of 0.5 to 1 microg/ml. Itraconazole had MIC(90)s of 0.06 microg/ml for H. capsulatum, 0.125 microg/ml for B. dermatitidis, and 1 microg/ml for C. immitis. The MIC(90)s of voriconazole were 0.25 microg/ml for all three fungi. Amphotericin B was fungicidal for B. dermatitidis and H. capsulatum with MFCs at which 90% of strains tested are killed (MFC(90)s) of 0.5 and 2 microg/ml, respectively. It was less active against C. immitis, with MFCs ranging from 0.5 to >16 microg/ml. Voriconazole and itraconazole were lethal for most isolates of B. dermatitidis, with MFC(50)s and MFC(90)s of 0.125 and 4 microg/ml, respectively. Both azoles were fungicidal for some isolates of H. capsulatum, with MFC(50)s of 2 and 8 microg/ml for itraconazole and voriconazole, respectively; neither had a lethal effect upon C. immitis. Our results suggest that voriconazole possesses promising activity against these important human pathogens.     

In vitro activity of E1210, a novel antifungal, against clinically important yeasts and molds

E1210 is a new antifungal compound with a novel mechanism of action and broad spectrum of antifungal activity. We investigated the in vitro antifungal activities of E1210 compared to those of fluconazole, itraconazole, voriconazole, amphotericin B, and micafungin against clinical fungal isolates. E1210 showed potent activities against most Candida spp. (MIC(90) of ≤0.008 to 0.06 μg/ml), except for Candida krusei (MICs of 2 to >32 μg/ml). E1210 showed equally potent activities against fluconazole-resistant and fluconazole-susceptible Candida strains. E1210 also had potent activities against various filamentous fungi, including Aspergillus fumigatus (MIC(90) of 0.13 μg/ml). E1210 was also active against Fusarium solani and some black molds. Of note, E1210 showed the greatest activities against Pseudallescheria boydii (MICs of 0.03 to 0.13 μg/ml), Scedosporium prolificans (MIC of 0.03 μg/ml), and Paecilomyces lilacinus (MICs of 0.06 μg/ml) among the compounds tested. The antifungal action of E1210 was fungistatic, but E1210 showed no trailing growth of Candida albicans, which has often been observed with fluconazole. In a cytotoxicity assay using human HK-2 cells, E1210 showed toxicity as low as that of fluconazole. Based on these results, E1210 is likely to be a promising antifungal agent for the treatment of invasive fungal infections.     

Trends in antifungal drug susceptibility of Cryptococcus neoformans isolates obtained through population-based surveillance in South Africa in 2002-2003 and 2007-2008

Cryptococcus neoformans is the most common cause of meningitis among adult South Africans with HIV infection/AIDS. Widespread use of fluconazole for treatment of cryptococcal meningitis and other HIV-associated opportunistic fungal infections in South Africa may lead to the emergence of isolates with reduced fluconazole susceptibility. MIC testing using a reference broth microdilution method was used to determine if isolates with reduced susceptibility to fluconazole or amphotericin B had emerged among cases of incident disease. Incident isolates were tested from two surveillance periods (2002-2003 and 2007-2008) when population-based surveillance was conducted in Gauteng Province, South Africa. These isolates were also tested for susceptibility to flucytosine, itraconazole, voriconazole, and posaconazole. Serially collected isolate pairs from cases at several large South African hospitals were also tested for susceptibility to fluconazole. Of the 487 incident isolates tested, only 3 (0.6%) demonstrated a fluconazole MIC of ≥ 16 μg/ml; all of these isolates were from 2002-2003. All incident isolates were inhibited by very low concentrations of amphotericin B and exhibited very low MICs to voriconazole and posaconazole. Of 67 cases with serially collected isolate pairs, only 1 case was detected where the isolate collected more than 30 days later had a fluconazole MIC value significantly higher than the MIC of the corresponding incident isolate. Although routine antifungal susceptibility testing of incident isolates is not currently recommended in clinical settings, it is still clearly important for public health to periodically monitor for the emergence of resistance.     

Comparison of NCCLS microdilution method and Etest in antifungal susceptibility testing of clinical Trichosporon asahii isolates

We investigated the in vitro activity of amphotericin B, fluconazole, and itraconazole against clinical Trichosporon asahii isolates (n = 43) by NCCLS M27A reference microdilution method and explored the correlation between Etest and NCCLS reference method. Microdilution MIC ranges following 48 h of incubation were 1-8, 0.25-16, and 0.06-4 microg/ml for amphotericin B, fluconazole, and itraconazole, respectively. The corresponding Etest MIC ranges were determined as 0.125- > 8, 0.25- > 64, and 0.03-8 microg/ml. Of interest, Etest tended to produce lower amphotericin B MICs and widen the MIC range compared to microdilution. The influence of Etest on fluconazole and itraconazole MICs was in contrary with that observed for amphotericin B. Etest MICs of fluconazole and itraconazole tended to be higher than microdilution MICs. The wider range of amphotericin B MICs obtained by using Etest methodology may facilitate discrimination of isolates with reduced susceptibility to amphotericin B. However, clinical significance of these findings remain yet unknown and determination of MIC breakpoint values is required.