In vitro activity of SCH-56592 and comparison with activities of amphotericin B and itraconazole against Aspergillus spp.

In this study, we investigated the in vitro activity of SCH-56592 (SCH), a new triazole antifungal agent. We compared the activity of SCH with those of itraconazole (ITZ) and amphotericin B (AB) against 60 clinical isolates of Aspergillus spp. by using a microtiter format. Incubation was done at 37 degrees C for 48 h, and MIC endpoints (no growth) were read visually. The medium used for all of the drugs was RPMI 1640 buffered with morpholinepropanesulfonic acid (MOPS) and supplemented with 2% glucose. MICs and minimum fungicidal concentrations (MFCs; killing of > or = 99.99%) were measured for all isolates. The geometric mean (GM) MICs and ranges (in micrograms per milliliter) were as follows: SCH, 0.09 and < or = 0.01 to 1; ITZ, 0.25 and 0.06 to 32; AB, 1.46 and 0.25 to 32. Aspergillus terreus (n = 7) was markedly more susceptible to SCH (GM, 0.05 microg/ml) and ITZ (GM, 0.07 microg/ml) than to AB (GM, 8.8 microg/ml). For all isolates, the GM MFCs and ranges (in micrograms per milliliter) were as follows: SCH, 3.64 and 0.125 to 16; ITZ, 15.09 and 0.125 to 32; AB, 10.3 and 1 to 32. In the drug concentration range tested, 71, 32, and 64% of the isolates against which SCH, ITZ, and AB, respectively, were tested were killed. A reproducibility study was performed with 20% of the isolates; for 11 of the 12 isolates retested, the MIC was the same or within 1 well of the original MIC of each drug. Therefore, in vitro mould testing of SCH is feasible and reproducible. SCH was found to be very active against all species of Aspergillus and at lower concentrations than either ITZ or AB.

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In Vitro Activity of the Echinocandin Antifungal Agent LY303,366 in Comparison with Itraconazole and Amphotericin B against Aspergillus spp

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.42.10.2726 ◽

1998 ◽

Vol 42 (10) ◽

pp. 2726-2730 ◽

Cited By ~ 59

Author(s):

Karen L. Oakley ◽

Caroline B. Moore ◽

David W. Denning

Keyword(s):

Amphotericin B ◽

Antifungal Agent ◽

Geometric Mean ◽

Vitro Activity ◽

In Vitro Activity ◽

End Point ◽

Inhibition Of Growth ◽

Reproducibility Study ◽

Minimal Effective Concentration

ABSTRACT LY303,366 (LY) is a novel derivative of the echinocandin class of antifungal agents. The in vitro activities of LY, itraconazole (ITZ), and amphotericin B (AMB) were assessed against 60Aspergillus isolates, including 35 isolates of A. fumigatus, eight isolates of A. terreus, eight isolates of A. flavus, eight isolates of A. niger and one isolate of A. nidulans. Four A. fumigatus isolates were resistant to ITZ. Susceptibility testing for all drugs was performed with a broth microdilution procedure. LY was tested in two media: antibiotic medium 3 (AM3) and Casitone with 2% glucose (CAS) with an inoculum of 2 × 103spores/ml. ITZ and AMB were tested in RPMI 1640 with 2% glucose with an inoculum of 1 × 106 spores/ml. All tests were incubated at 37°C for 48 h. A novel end point was used to determine a minimal effective concentration (MEC) for LY, i.e., almost complete inhibition of growth save a few tiny spherical colonies attached to the microplate. MICs were measured for ITZ and AMB with a no-growth end point. Ranges and geometric mean (GM) MECs were from 0.0018 to >0.5 and 0.0039 mg/liter and from 0.0018 to >0.5 and 0.008 mg/liter for LY in AM3 and LY in CAS, respectively. Differences between species were apparent, with A. flavus being significantly less susceptible to LY than any other species tested with both media (P ≤ 0.05). Ranges and GM MICs were from 0.125 to >16 and 0.7 mg/liter for ITZ and from 0.25 to 16 and 1.78 mg/liter for AMB. Minimal fungicidal concentrations (MFCs) were also determined for all drugs. GM MFCs were 0.018, 0.09, 19.76, and 12.64 mg/liter for LY in AM3, LY in CAS, ITZ, and AMB, respectively. LY in AM3 and LY in CAS were fungicidal for 86.7 and 68% of isolates, respectively (98% killing). In comparison, ITZ and AMB were fungicidal for 35 and 70% of isolates, respectively (99.99% killing). A reproducibility study was performed on 20% of the isolates. For 12 isolates retested, the MEC or MIC was the same or was within 1 dilution of the original value for 11, 11, 10, and 9 isolates for LY in AM3, LY in CAS, ITZ, and AMB, respectively. In conclusion, LY seems to be a promising antifungal agent with excellent in vitro activity against Aspergillusspp.

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Comparison of In Vitro Activity of Liposomal Nystatin againstAspergillus Species with Those of Nystatin, Amphotericin B (AB) Deoxycholate, AB Colloidal Dispersion, Liposomal AB, AB Lipid Complex, and Itraconazole

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.43.5.1264 ◽

1999 ◽

Vol 43 (5) ◽

pp. 1264-1266 ◽

Cited By ~ 37

Author(s):

Karen L. Oakley ◽

Caroline B. Moore ◽

David W. Denning

Keyword(s):

Amphotericin B ◽

Aspergillus Terreus ◽

Antifungal Agents ◽

Geometric Mean ◽

Colloidal Dispersion ◽

Vitro Activity ◽

In Vitro Activity ◽

Lipid Complex

ABSTRACT We compared the in vitro activity of liposomal nystatin (Nyotran) with those of other antifungal agents against 60Aspergillus isolates. Twelve isolates were itraconazole resistant. For all isolates, geometric mean (GM) MICs (micrograms per milliliter) were 2.30 for liposomal nystatin, 0.58 for itraconazole, 0.86 for amphotericin B (AB) deoxycholate, 9.51 for nystatin, 2.07 for liposomal AB, 2.57 for AB lipid complex, and 0.86 for AB colloidal dispersion. Aspergillus terreus (GM, 8.72 μg/ml; range, 8 to 16 μg/ml) was significantly less susceptible to all of the polyene drugs than all other species (P = 0.0001).

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In Vitro Activity of the New Triazole BMS-207147 againstAspergillus Species in Comparison with Itraconazole and Amphotericin B

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.44.2.441-443.2000 ◽

2000 ◽

Vol 44 (2) ◽

pp. 441-443 ◽

Cited By ~ 52

Author(s):

Caroline B. Moore ◽

Caroline M. Walls ◽

David W. Denning

Keyword(s):

Aspergillus Fumigatus ◽

Amphotericin B ◽

Geometric Mean ◽

Vitro Activity ◽

Clinical Isolates ◽

In Vitro Activity ◽

High Concentrations

ABSTRACT The in vitro activity of BMS-207147 against 80 clinical isolates ofAspergillus was compared with that of itraconazole and amphotericin B, using a validated microtiter method. Geometric mean MICs (in μg/ml) were as follows: 1.71 for BMS-207147, 0.67 for itraconazole, and 0.63 for amphotericin B. The range of concentrations of each drug was 0.125 to >16 μg/ml. Aspergillus fumigatus was significantly more susceptible to BMS-207147 (P < 0.05) than A. terreusand A. flavus. No BMS-207147-resistant A. fumigatus isolates were identified, though eight itraconazole-resistant (MIC, >8 μg/ml) isolates were. BMS-207147 is active against Aspergillus spp. at slightly high concentrations compared with itraconazole and amphotericin B.

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In vitro activity of olorofim against clinical isolates of Scedosporium species and Lomentospora prolificans using EUCAST and CLSI methodologies

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkaa351 ◽

2020 ◽

Vol 75 (12) ◽

pp. 3582-3585

Author(s):

Olga Rivero-Menendez ◽

Manuel Cuenca-Estrella ◽

Ana Alastruey-Izquierdo

Keyword(s):

Amphotericin B ◽

Susceptibility Testing ◽

Antifungal Susceptibility ◽

Vitro Activity ◽

Clinical Isolates ◽

Scedosporium Apiospermum ◽

In Vitro Activity ◽

Scedosporium Dehoogii ◽

Scedosporium Species

Abstract Objectives To evaluate the in vitro activity of olorofim, a new broad-spectrum antifungal with a novel mechanism of action, against a collection of 123 Spanish clinical isolates belonging to five Scedosporium species and Lomentospora prolificans. Methods The activity of olorofim against Scedosporium apiospermum (n = 30), Scedosporium boydii (n = 30), Scedosporium ellipsoideum (n = 10), Scedosporium aurantiacum (n = 20), Scedosporium dehoogii (n = 3) and Lomentospora prolificans (n = 30) was compared with that of amphotericin B, voriconazole, isavuconazole and micafungin by performing EUCAST and CLSI reference methods for antifungal susceptibility testing. Results Amphotericin B and isavuconazole showed MICs ≥2 mg/L for all the species evaluated and voriconazole was moderately active (GM, MIC50 and MIC90 values ≤2 mg/L) against all of them except L. prolificans. Micafungin was effective against S. apiospermum complex strains, but exhibited elevated MECs for S. dehoogii and S. aurantiacum. Olorofim showed low MICs for all the Scedosporium strains tested (GM values were lower than 0.130 and 0.339 by the EUCAST method and the CLSI method, respectively, for all of the species), including those belonging to the MDR species L. prolificans, for which GM values were 0.115 and 0.225 mg/L by the EUCAST method and the CLSI method, respectively, while the GMs for the rest of the antifungals evaluated were higher than 3.732 mg/L using both methodologies. Conclusions Olorofim displayed promising in vitro activity against the Scedosporium and L. prolificans strains tested, some of which have reduced susceptibility to the antifungals that are currently in use.

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In Vitro Activities of Terbinafine againstAspergillus Species in Comparison with Those of Itraconazole and Amphotericin B

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.45.6.1882-1885.2001 ◽

2001 ◽

Vol 45 (6) ◽

pp. 1882-1885 ◽

Cited By ~ 32

Author(s):

Caroline B. Moore ◽

Caroline M. Walls ◽

David W. Denning

Keyword(s):

Aspergillus Fumigatus ◽

Amphotericin B ◽

Geometric Mean ◽

Vitro Activity ◽

Clinical Correlation ◽

In Vitro Activity

ABSTRACT Compared with the in vitro activities of itraconazole (geometric mean MIC [GM], 0.56 μg/ml) and amphotericin B (GM, 0.66 μg/ml), the in vitro activity of terbinafine was inferior againstAspergillus fumigatus (GM, 19.03 μg/ml) (P < 0.05) and superior against A. flavus(GM, 0.10 μg/ml), A. terreus (GM, 0.16 μg/ml), andA. niger (GM, 0.19 μg/ml). Clinical correlation is required, as trailing endpoints are problematic.

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Comparison of the in-vitro activity of voriconazole (UK-109,496), itraconazole and amphotericin B against clinical isolates of Aspergillus fumigatus

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/42.4.531 ◽

1998 ◽

Vol 42 (4) ◽

pp. 531-533 ◽

Cited By ~ 67

Author(s):

M. Cuenca-Estrella ◽

J. L. Rodriguez-Tudela ◽

E. Mellado ◽

J. V. Martinez-Suarez ◽

A. Monzon

Keyword(s):

Aspergillus Fumigatus ◽

Amphotericin B ◽

Vitro Activity ◽

Clinical Isolates ◽

In Vitro Activity

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In Vitro Susceptibilities of 217 Clinical Isolates of Zygomycetes to Conventional and New Antifungal Agents

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00452-07 ◽

2007 ◽

Vol 51 (7) ◽

pp. 2587-2590 ◽

Cited By ~ 184

Author(s):

Nikolaos G. Almyroudis ◽

Deanna A. Sutton ◽

Annette W. Fothergill ◽

Michael G. Rinaldi ◽

Shimon Kusne

Keyword(s):

Amphotericin B ◽

Clinical Efficacy ◽

Antifungal Agents ◽

Vitro Activity ◽

Clinical Isolates ◽

In Vitro Activity ◽

Cunninghamella Bertholletiae

ABSTRACT We evaluated the in vitro susceptibilities of 217 zygomycetes to amphotericin B, ketoconazole, fluconazole, itraconazole, voriconazole, posaconazole, caspofungin, and flucytosine. The significant in vitro activity of posaconazole against several species appears to support its reported clinical efficacy. Decreased susceptibility to amphotericin B was noted with Cunninghamella bertholletiae.

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