In vitro susceptibilities of clinical yeast isolates to a new echinocandin derivative, LY303366, and other antifungal agents.

LY303366 is a new semisynthetic echinocandin derivative with potent, broad-spectrum fungicidal activity. We investigated the in vitro activity of LY303366, amphotericin B, flucytosine (5FC), fluconazole, and itraconazole against 435 clinical yeast isolates (413 Candida and 22 Saccharomyces cerevisiae isolates) obtained from over 30 different medical centers. MICs for all five antifungal agents were determined by the National Committee for Clinical Laboratory Standards method with RPMI 1640 test medium. LY303366 was also tested in antibiotic medium 3 as specified by the manufacturer. Overall, LY303366 was quite active against all of the yeast isolates when tested in RPMI 1640 (MIC at which 90% of the isolates are inhibited [MIC90], 1.0 microg/ml) but appeared to be considerably more potent when tested in antibiotic medium 3 (MIC90, 0.03 microg/ml). When tested in antibiotic medium 3, LY303366 was 16- to >2,000-fold more active than itraconazole, fluconazole, amphotericin B, or 5FC against all species except Candida parapsilosis. When tested in RPMI 1640, LY303366 was comparable to amphotericin B and itraconazole and more active than fluconazole and 5FC. All of the isolates for which fluconazole and itraconazole had elevated MICs (> or = 128 and > or = 2.0 microg/ml, respectively) were inhibited by < or = 0.007 microg of LY303366/ml when tested in antibiotic medium 3 and < or = 0.5 microg/ml when tested in RPMI 1640. Based on these studies, LY303366 has promising antifungal activity and warrants further in vitro and in vivo investigation.     

Susceptibility of fluconazole-resistant clinical isolates of Candida spp. to echinocandin LY303366, itraconazole and amphotericin B

The in vitro activity of LY303366 was compared with those of itraconazole and amphotericin B against 156 fluconazole-resistant (MIC > or = 16 mg/L) clinical isolates of CANDIDA: spp. An adaptation of the NCCLS reference method was employed for determination of MICs. LY303366 was more potent than either itraconazole or amphotericin B against Candida albicans, Candida glabrata, Candida krusei and Candida tropicalis, even against isolates with itraconazole MICs > or = 1 mg/L. LY303366 was less potent in vitro against Candida parapsilosis and Candida guilliermondii isolates. LY303366 has promising antifungal activity and warrants further investigation.     

In vitro activity of voriconazole,itraconazole, caspofungin,anidulafungin (VER002, LY303366) and amphotericin B against aspergillus spp

Voriconazole, anidulafungin (VER002, LY303366) and caspofungin are promising antifungal agents which provide a good protection against a variety of fungi, including yeasts and filamentous fungi. In this study, we tested the in vitro efficacy of voriconazole, itraconazole, caspofungin, anidulafungin (VER002, LY303366) and amphotericin B, against different species of Aspergillus spp. isolated from clinical specimens, using a microdilution broth method and following the NCCLS guidelines (document M38-P). We also evaluated the effect that time readings have on MIC results. For caspofungin, we determined the minimun effective concentration (MEC), defined like the lowest concentration of caspofungin causing abnormal hyphal growth. Anidulafungin (VER002, LY303366) was the most active antifungal agent tested with MIC(90) of < or =0,03 mg/L. The activity of voriconazole, and itraconazole very similar with MIC(90) of 0,12 mg/L, 0,12 mg/L respectively. For caspofungin the MEC(90) was of 0,25 mg/L. Amphotericin B was the lest active antifungal agent studied with MIC(90) of 1 mg/L. There were no differences between MIC values at 48 and 72 h. These data demonstrate promising activity of voriconazole, anidulafungin (VER002, LY303366) and caspofungin against Apergillus spp.     

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

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) and Candida 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.     

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.     

Activity of MK-0991 (l-743,872), a new echinocandin,compared with those of LY303366 and four other antifungal agents tested against blood stream isolates of Candida spp.

MK-0991 (formerly L-743,872) is a water soluble semisynthetic echinocandin that possess potent, broad-spectrum antifungal activity. We evaluated the in vitro activity of MK-0991 and an echinocandin derivative LY303366, compared with that of itraconazole, fluconazole, amphotericin B and 5-flucytosine against 400 blood stream isolates of Candida spp. (nine species) obtained from more than 30 different medical centers. MICs for all antifungal drugs were determined by the NCCLS method using RPMI 1640 test medium. Both MK-0991 and LY303366 were very active against all Candida spp. isolates (MIC₉₀, 0.25 and 1 μg/mL, respectively). MK-0991 was twofold to 256-fold more active than amphotericin B, fluconazole, itraconazole (except against C. parapsilosis), and 5-flucytosine (except against C. glabrata and C. parapsilosis). LY303366 was comparable to MK-0991, but was fourfold less active against C. tropicalis (MIC₉₀, 0.5 versus 0.12 μg/mL) and C. parapsilosis (MIC₉₀, >2 versus 1 μg/mL). All of the isolates for which fluconazole and itraconazole had elevated MICs (≥64 μg/mL and ≥1 μg/mL, respectively) were inhibited by ≤0.5 μg/mL of MK-0991 and LY303366. These results suggest both MK-0991 and LY303366 possess promising antifungal activity and further in vitro and in vivo investigations are warranted.     

In Vitro Activity of Two Echinocandin Derivatives, LY303366 and MK-0991 (L-743,792), Against Clinical Isolates of Aspergillus, Fusarium, Rhizopus, and Other Filamentous Fungi

LY303366 and MK-0991 (previously L-743,792) are new echinocandin derivatives with excellent broad-spectrum antifungal activity. We investigated the in vitro activity of LY303366, MK-0991, itraconazole, amphotericin B, and 5-flucytosine against 51 clinical isolates of filamentous fungi, including Aspergillus flavus (10), A. fumigatus (12), Fusarium spp. (13), Rhizopus spp. (6), Pseudallescheria boydii (5), and one isolate each of Acremonium spp., A. niger, A. terreus, Paecilomyces spp., and Trichoderma spp. In vitro susceptibility testing was performed using a microdilution broth method performed according to National Committee for Clinical Laboratory Standards guidelines. LY303366 was two- to fourfold more active than MK-0991 against A. flavus, A. fumigatus, and Trichoderma spp. Both LY303366 and MK-0991 were considerably more active (MIC₉₀ of 0.03–0.12 μg/mL) than itraconazole, amphotericin B, and 5-flucytosine against Aspergillus spp., but were less active than itraconazole and amphotericin B against Rhizopus spp. MK-0991 was more active than either LY303366 or itraconazole against Acremonium spp., Paecilomyces spp., and P. boydii. These data demonstrate promising activity of both LY303366 and MK-0991 against Aspergillus spp. and other species of filamentous fungi that are likely to be encountered clinically. Further in vitro and in vivo investigation is indicated.     

Initial results from a longitudinal international surveillance programme for anidulafungin (2003)

OBJECTIVES: This longitudinal study evaluated the in vitro activity of anidulafungin against 880 clinical yeast isolates and 68 mould isolates from 64 medical centres in North America, Latin America and Europe. METHODS: MICs of anidulafungin, amphotericin B, 5-fluorocytosine, fluconazole, itraconazole, ketoconazole and voriconazole were determined using reference method (M27-A2) guidelines. The M38-A reference method was used for the filamentous fungi, including determination of minimum effective concentrations (MECs) of anidulafungin. RESULTS: Anidulafungin was more active when compared with fluconazole and itraconazole for Candida albicans (MIC(90), 0.06 mg/L), Candida tropicalis (MIC(90), 0.06 mg/L), Candida glabrata (MIC(90), 0.12 mg/L), Candida krusei (MIC(90), 0.06 mg/L) and Candida lusitaniae (MIC(90), 1 mg/L) as well as the less-often encountered yeast species. Anidulafungin was less active against Candida parapsilosis, Candida guilliermondii and Candida famata (MIC(50), 1-2 mg/L). Anidulafungin also exhibited excellent activity against all Aspergillus spp. (MEC(90), < or =0.03 mg/L). Anidulafungin was also evaluated comparing two end point reading criteria and two incubation intervals. Data indicate that longer incubation periods do not significantly influence overall MIC ranges. These international surveillance results for anidulafungin confirm the activity observed in studies of smaller numbers of isolates.     

In vitro activities of posaconazole, fluconazole, itraconazole, voriconazole, and amphotericin B against a large collection of clinically important molds and yeasts

The in vitro activity of the novel triazole antifungal agent posaconazole (Noxafil; SCH 56592) was assessed in 45 laboratories against approximately 19,000 clinically important strains of yeasts and molds. The activity of posaconazole was compared with those of itraconazole, fluconazole, voriconazole, and amphotericin B against subsets of the isolates. Strains were tested utilizing Clinical and Laboratory Standards Institute broth microdilution methods using RPMI 1640 medium (except for amphotericin B, which was frequently tested in antibiotic medium 3). MICs were determined at the recommended endpoints and time intervals. Against all fungi in the database (22,850 MICs), the MIC(50) and MIC(90) values for posaconazole were 0.063 microg/ml and 1 mug/ml, respectively. MIC(90) values against all yeasts (18,351 MICs) and molds (4,499 MICs) were both 1 mug/ml. In comparative studies against subsets of the isolates, posaconazole was more active than, or within 1 dilution of, the comparator drugs itraconazole, fluconazole, voriconazole, and amphotericin B against approximately 7,000 isolates of Candida and Cryptococcus spp. Against all molds (1,702 MICs, including 1,423 MICs for Aspergillus isolates), posaconazole was more active than or equal to the comparator drugs in almost every category. Posaconazole was active against isolates of Candida and Aspergillus spp. that exhibit resistance to fluconazole, voriconazole, and amphotericin B and was much more active than the other triazoles against zygomycetes. Posaconazole exhibited potent antifungal activity against a wide variety of clinically important fungal pathogens and was frequently more active than other azoles and amphotericin B.     

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.     

Postantifungal effects of echinocandin, azole, and polyene antifungal agents against Candida albicans and Cryptococcus neoformans

The postantifungal effect (PAFE) of fluconazole, MK-0991, LY303366, and amphotericin B was determined against isolates of Candida albicans and Cryptococcus neoformans. Concentrations ranging from 0. 125 to 4 times the MIC were tested following exposure to the antifungal for 0.25 to 1 h. Combinations of azole and echinocandin antifungals (MK-0991 and LY303366) were tested against C. neoformans. Fluconazole displayed no measurable PAFE against Candida albicans or Cryptococcus neoformans, either alone or in combination with either echinocandin antifungal. MK-0991, LY303366, and amphotericin B displayed a prolonged PAFE of greater than 12 h against Candida spp. when tested at concentrations above the MIC for the organism and 0 to 2 h when tested at concentrations below the MIC for the organism.     

In vitro susceptibilities of zygomycetes to conventional and new antifungals

In vitro susceptibilities of 36 zygomycete isolates, belonging to six genera, to itraconazole, posaconazole, voriconazole, terbinafine, amphotericin B and 5-fluorocytosine were determined by using a broth microdilution adaptation of the National Committee for Clinical Laboratory Standards M-38P reference method. The influence of incubation time on MIC values, and the performance of a spectrophotometric method for MIC determination in comparison with the visual reference method, were also evaluated. Amphotericin B was active against most of the isolates. All the isolates were highly resistant to 5-fluorocytosine (MICs > 256 mg/L). Voriconazole was significantly less active than the other drugs with an overall MIC(90) (MIC at which 90% of the isolates were inhibited) of 32 mg/L. In contrast, posaconazole showed good activity (MIC(90) 1 mg/L). A wide range of MICs, from 0.03 to > or =32 mg/L, was obtained for itraconazole and terbinafine. Differences in susceptibility between and within genera were noted. Rhizopus spp. were significantly less susceptible to itraconazole, posaconazole, terbinafine and amphotericin B than Absidia spp., and less susceptible than Mucor spp. to amphotericin B. Terbinafine appeared to be more active against Rhizopus microsporus than against Rhizopus oryzae (geometric mean MIC of 0.15 and 64 mg/L, respectively). The activity of the drugs was dependent on the incubation period. A significant increase in MICs was noted between 24 and 48 h of incubation. On the other hand, the two methods used for MIC determination (visual and spectrophotometric readings) showed good agreement. These results suggest that the zygomycetes are a heterogeneous group for antifungal susceptibility. Some of the conventional and new antifungals are effective in vitro; their efficacies in vivo remain to be determined. The spectrophotometric method appears to be a valuable alternative to the visual method for MIC determination for zygomycetes.     

Susceptibility of clinical isolates of Candida lusitaniae to five systemic antifungal agents

OBJECTIVES: The aim of the present study was to expand the MIC database for Candida lusitaniae in order to further determine its antifungal susceptibility pattern. METHODS: The activities of amphotericin B, fluconazole, itraconazole, voriconazole and flucytosine were determined in vitro against 80 clinical isolates of C. lusitaniae. A set of 59 clinical isolates of Candida albicans and of 51 isolates of Candida glabrata was included to compare the susceptibilities to amphotericin B. The MICs were determined by Etest with RPMI 1640 agar, and with both this medium and antibiotic medium 3 (AM3) agar for testing of amphotericin B. RESULTS: All isolates were highly susceptible to fluconazole. The susceptibility to itraconazole was good; only 4% of isolates had dose-dependent susceptibility (MICs 0.25-0.5 mg/L). Voriconazole was very active in vitro (100% of isolates were inhibited at < or =0.094 mg/L). Flucytosine MICs ranged widely (0.004->32 mg/L). The set included 19% of flucytosine-resistant isolates. For amphotericin B, 100% of isolates were inhibited at < or =0.75 mg/L (MIC(50) 0.047 mg/L; MIC(90) 0.19 mg/L) and at < or =4 mg/L (MIC(50) 0.25 mg/L; MIC(90) 0.75 mg/L) on RPMI and on AM3, respectively. A single isolate was categorized as resistant to amphotericin B (MIC 0.75 and 4 mg/L on RPMI and on AM3, respectively). Amphotericin B thus appeared very active in vitro against C. lusitaniae. Whatever the test medium, the level of susceptibility of C. lusitaniae to amphotericin B did not differ much from those of C. albicans and C. glabrata. CONCLUSION: C. lusitaniae appears to be susceptible to amphotericin B, azole antifungal agents, and, to a lesser extent, flucytosine.     

In vitro studies of two triazole antifungal agents (voriconazole [UK-109,496] and fluconazole) against Candida species.

A new triazole derivative (voriconazole or UK-109,496) and fluconazole were tested against 249 isolates of Candida spp. representing six species. Voriconazole was 10 to 100 times more potent than fluconazole. Strains with decreased susceptibility to fluconazole were inhibited by relatively low concentrations of voriconazole.     

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.     

Antifungal susceptibility of Cryptococcus neoformans and Cryptococcus gattii isolates from decayed wood of trunk hollows of Ficus religiosa and Syzygium cumini trees in north-western India

BACKGROUND: We present antifungal susceptibility data on environmental isolates of Cryptococcus neoformans (serotype A, n=117) and Cryptococcus gattii (serotype B, n=65) cultured from decayed wood of trunk hollows of Ficus religiosa and Syzygium cumini trees. METHODS: Susceptibilities to amphotericin B, fluconazole, ketoconazole, itraconazole and voriconazole were determined by using Etest. The MICs were read after 48 h as per the guidelines provided by the manufacturer. RESULTS: The MIC90s and susceptibility ranges for C. neoformans isolates were as follows: 0.094 (0.004-0.25) mg/L for amphotericin B, 4 (0.032-12) mg/L for fluconazole, 0.094 (0.004-0.75) mg/L for itraconazole, 0.064 (0.002-0.19) mg/L for ketoconazole, and 0.047 (0.006-0.125) mg/L for voriconazole, whereas for C. gattii isolates these were 0.125 (0.023-0.5) mg/L for amphotericin B, 8 (0.032-16) mg/L for fluconazole, 0.75 (0.006-2) mg/L for itraconazole, 0.125 (0.003-0.19) mg/L for ketoconazole, and 0.094 (0.004-0.125) mg/L for voriconazole. A comparison of the geometric means of MICs (mg/L) revealed that C. gattii was less susceptible than C. neoformans to amphotericin B (0.075 versus 0.051, P=0.0003), fluconazole (2.912 versus 2.316, P=0.003), itraconazole (0.198 versus 0.0344, P<0.0001), ketoconazole (0.072 versus 0.037, P<0.0001), and voriconazole (0.045 versus 0.023, P<0.0001). CONCLUSIONS: The antifungal susceptibility data obtained in this study indicate that the occurrence of primary resistance among environmental isolates of C. neoformans serotype A and C. gattii serotype B is rare, and serotype B isolates are less susceptible than serotype A isolates.     

Activity of a new triazole, Sch 56592, compared with those of four other antifungal agents tested against clinical isolates of Candida spp. and Saccharomyces cerevisiae.

Sch 56592 is a new triazole agent with potent, broad-spectrum antifungal activity. The in vitro activities of Sch 56592, itraconazole, fluconazole, amphotericin B, and flucytosine (5-FC) against 404 clinical isolates of Candida spp. (382 isolates) and Saccharomyces cerevisiae (22 isolates) were investigated. In vitro susceptibility testing was performed by a broth microdilution method performed according to National Committee for Clinical Laboratory Standards guidelines. Overall, Sch 56592 was very active (MIC at which 90% of isolates are inhibited [MIC90], 0.5 microgram/ml) against these yeast isolates. Sch 56592 was most active against Candida tropicalis, Candida parapsilosis, candida lusitaniae, and Candida stellatoidea (MIC90, < or = 0.12 microgram/ml) and was least active against Candida glabrata (MIC90, 2.0 micrograms/ml). Sch 56592 was 2- to 32-fold more active than amphotericin B and 5-FC against all species except C. glabrata. By comparison with the other triazoles, Sch 56592 was equivalent to itraconazole and greater than or equal to eightfold more active than fluconazole. On the basis of these results, Sch 56592 has promising antifungal activity, and further in vitro and in vivo investigations are warranted.     

Influence of Human Serum on Antifungal Pharmacodynamics with Candida albicans

Antifungal susceptibilities (NCCLS, approved standard M27-A, 1997) were determined for the reference strain ATCC 90028 and 21 clinical isolates of Candida albicans with varying levels of fluconazole susceptibility using RPMI 1640 (RPMI) and 80% fresh human serum-20% RPMI (serum). Sixty-four percent (14 of 22) of the isolates tested demonstrated significant decreases (> or = 4-fold) in fluconazole MICs in the presence of serum, and the remaining eight isolates exhibited no change. Itraconazole and ketoconazole, two highly protein-bound antifungal agents, had MICs in serum that were increased or unchanged for 46% (10 of 22) and 41% (9 of 22) of the isolates, respectively. All 10 isolates tested against an investigational antifungal agent, LY303366, demonstrated significant increases in the MIC required in serum, while differences in amphotericin B MICs in the two media were not observed. Four of 10 isolates tested demonstrated fourfold higher flucytosine MICs in serum than in RPMI. Postantifungal effects (PAFEs) and 24-h kill curves were determined by standard methods for selected isolates. At the MIC, fluconazole, itraconazole, ketoconazole, flucytosine, and LY303366 kill curves and PAFEs in RPMI were similar to those in serum. Isolates of fluconazole-resistant C. albicans required lower MICs in serum than in RPMI, without relative increases in fungal killing or PAFEs. Isolates tested against amphotericin B demonstrated significantly reduced killing and shorter PAFEs in serum than in RPMI without observable changes in MIC. In conclusion, antifungal pharmacodynamics in RPMI did not consistently predict antifungal activity in serum for azoles and amphotericin B. Generally speaking, antifungal agents with high protein binding exhibited some form of reduced activity (MIC, killing, or PAFE) in the presence of serum compared to those with low protein binding.     

In vitro susceptibility of Candida dubliniensis to current and new antifungal agents

BACKGROUND: Candida dubliniensis is a recently described Candida species closely related to Candida albicans, which has been associated with oral candidiasis in HIV-infected patients. Fluconazole-resistant strains of C. dubliniensis are easily obtained in vitro and this fact could be a complication if this resistance develops during treatment with this drug. METHODS: In the present study, the in vitro antifungal susceptibilities of 36 C. dubliniensis clinical isolates and culture strains to current and new antifungal agents, such as amphotericin B (AMB), amphotericin B lipid complex (ABLC), amphotericin B colloidal dispersion (ABCD), 5-fluorocytosine (5FC), fluconazole (FLC), itraconazole (ITC), ketoconazole (KTC), liposomal amphoteri- cin B (LAMB), liposomal nystatin (LNYT), LY303366 (LY), SCH56592 (SCH), and voriconazole (VRC), were determined according to the National Committee for Clinical Laboratory Standards M27-A broth microdilution method for yeasts. RESULTS: Most isolates of C. dubliniensis were susceptible to both new and current antifungal drugs, with 75.9% isolates susceptible to KTC, 86.2% to FLC and to ITC, and approximately 100% to the other antifungal agents tested. The cross-resistance phenotypes are detailed. Four isolates were resistant (MIC > or =64 microg/ml) to FLC. These 4 isolates were also resistant to KTC, and 3 of them were also resistant to ITC (MIC > or =1 microg/ml for both agents). However, these isolates were highly susceptible to 5FC and all polyene formulations (AMB, ABLC, ABCD, LAMB, and LNYT), triazole (SCH and VRC) and echinocandin (LY) antifungal agents. CONCLUSION: The new liposomal and lipidic formulations of AMB, LNYT, and the new triazoles and echinocandins may provide new alternatives to FLC for the treatment of infections by C. dubliniensis.     

Rates of antifungal resistance among Spanish clinical isolates of Cryptococcus neoformans var. neoformans

OBJECTIVES: Activities in vitro of six antifungal agents were tested against a collection of 317 Cryptococcus neoformans var. neoformans clinical isolates. METHODS: The procedure described in document 7.1 by the European Committee on Antibiotic Susceptibility Testing with minor modifications was employed. RESULTS: Amphotericin B, itraconazole, voriconazole and ravuconazole exhibited a potent activity with geometric mean (GM) MICs under 0.26 mg/L. The GM MIC of flucytosine was 7.33 mg/L and that of fluconazole was 4.16 mg/L. The rates of antifungal resistance were 5.3% for amphotericin B, 0.9% for voriconazole and 3.1% for ravuconazole. Fifteen point eight per cent of strains had itraconazole MICs > or = 1 mg/L, and 46% of strains had flucytosine MICs > or = 8 mg/L. Fluconazole susceptibility (MIC < or = 8 mg/L) stood at 53.4%. CONCLUSIONS: The percentage of fluconazole susceptibility was significantly lower than that in other surveys. Cross-resistance to itraconazole was common (33.8%) but almost the whole collection was susceptible to voriconazole and ravuconazole. These results should be confirmed with prospective and population-based surveillance programmes.