scholarly journals 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.

1997 ◽  
Vol 41 (2) ◽  
pp. 233-235 ◽  
Author(s):  
M A Pfaller ◽  
S Messer ◽  
R N Jones
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Antifungal Activity ◽  
Amphotericin B ◽  
Clinical Laboratory ◽  
Clinical Isolates ◽  
National Committee ◽  
Candida Spp ◽  
In Vitro Susceptibility ◽  
Broth Microdilution Method

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.

scholarly journals 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

2002 ◽  
Vol 46 (4) ◽  
pp. 1032-1037 ◽  
Author(s):  
M. A. Pfaller ◽  
S. A. Messer ◽  
R. J. Hollis ◽  
R. N. Jones
Keyword(s):  
Amphotericin B ◽  
Filamentous Fungi ◽  
Antifungal Agents ◽  
Clinical Laboratory ◽  
The United States ◽  
Clinical Isolates ◽  
National Committee ◽  
Surveillance Program ◽  
In Vitro Susceptibility

ABSTRACT 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.

Use of spectrophotometric reading for in vitro antifungal susceptibility testing ofAspergillusspp.

1999 ◽  
Vol 45 (10) ◽  
pp. 871-874 ◽  
Author(s):  
Eric Dannaoui ◽  
Florence Persat ◽  
Marie-France Monier ◽  
Elisabeth Borel ◽  
Marie-Antoinette Piens ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Susceptibility Testing ◽  
Clinical Laboratory ◽  
Antifungal Susceptibility ◽  
Reference Method ◽  
Antifungal Susceptibility Testing ◽  
Aspergillus Species ◽  
National Committee ◽  
Broth Microdilution Method

A comparative study of visual and spectrophotometric MIC endpoint determinations for antifungal susceptibility testing of Aspergillus species was performed. A broth microdilution method adapted from the National Committee for Clinical Laboratory Standards (NCCLS) was used for susceptibility testing of 180 clinical isolates of Aspergillus species against amphotericin B and itraconazole. MICs were determined visually and spectrophotometrically at 490 nm after 24, 48, and 72h of incubation, and MIC pairs were compared. The agreement between the two methods was 99% for amphotericin B and ranged from 95 to 98% for itraconazole. It is concluded that spectrophotometric MIC endpoint determination is a valuable alternative to the visual reference method for susceptibility testing of Aspergillus species.Key words: antifungal, susceptibility testing, Aspergillus, spectrophotometric reading.

Amphotericin B in Lipid Emulsion: Stability, Compatibility, and In Vitro Antifungal Activity

1998 ◽  
Vol 42 (4) ◽  
pp. 762-766 ◽  
Author(s):  
Scott Walker ◽  
Sandra A. N. Tailor ◽  
Mark Lee ◽  
Lisa Louie ◽  
Marie Louie ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Amphotericin B ◽  
Clinical Laboratory ◽  
National Committee ◽  
Compatibility Study ◽  
The Stability ◽  
Few Data ◽  
Reference Strains ◽  
In Vitro Antifungal Activity

ABSTRACT Newer formulations of amphotericin B (AmB) complexed with liposomes or lipid suspensions have been developed. Preliminary studies have suggested that AmB in Intralipid (IL) may be as effective as, but less toxic than, conventional formulations of AmB, but few data are available regarding its stability, compatibility, or in vitro antifungal activity. A compatibility study was done to evaluate the effects of AmB concentrations in IL containing either 10 or 20% soybean oil. The effects of temperature, shaking, and AmB and IL concentrations on the stability of AmB-IL suspensions were analyzed by visual inspection and liquid chromatography. The in vitro antifungal activity of AmB-IL, compared to that of AmB alone against reference strains of Candida species was determined by using a broth macrodilution method in accordance with National Committee for Clinical Laboratory Standards guidelines (M27-T). Samples of AmB-IL which were lightly shaken retained more than 90% of the AmB concentration over 21 days when stored at either 4 or 23°C. Varying the AmB concentration did not appear to affect the stability of AmB-IL. However, a precipitate was formed when mixtures with more than 30% lipid as a proportion of the total volume were centrifuged. AmB-IL and AmB alone had similar in vitro antifungal activities against reference strains of yeasts. Further pharmacologic and clinical studies with AmB-IL are warranted, although AmB should not be combined with IL in concentrations capable of producing a precipitate.

scholarly journals In Vitro Amphotericin B Resistance in Clinical Isolates of Aspergillus terreus, with a Head-to-Head Comparison to Voriconazole

1999 ◽  
Vol 37 (7) ◽  
pp. 2343-2345 ◽  
Author(s):  
Deanna A. Sutton ◽  
Stephen E. Sanche ◽  
Sanjay G. Revankar ◽  
Annette W. Fothergill ◽  
Michael G. Rinaldi
Keyword(s):  
Amphotericin B ◽  
Aspergillus Terreus ◽  
Clinical Laboratory ◽  
Immunocompromised Host ◽  
Clinical Isolates ◽  
National Committee ◽  
High Dose ◽  
Etiologic Agents ◽  
Disseminated Disease

Amphotericin B therapy continues to be the “gold standard” in the treatment of invasive aspergillosis in the immunocompromised host. Although Aspergillus fumigatus and Aspergillus flavus constitute the major species, several reports have described invasive pulmonary or disseminated disease due to the less common Aspergillus terreus and dismal clinical outcomes with high-dose amphotericin B. We therefore evaluated 101 clinical isolates of A. terreus for their susceptibility to amphotericin B and the investigational triazole voriconazole by using the National Committee for Clinical Laboratory Standards M27-A method modified for mould testing. Forty-eight-hour MICs indicated 98 and 0% resistance to amphotericin B and voriconazole, respectively. We conclude that A. terreus should be added to the list of etiologic agents refractory to conventional amphotericin B therapy and suggest the potential clinical utility of voriconazole in aspergillosis due to this species.

scholarly journals In Vitro Activities of Free and Lipid Formulations of Amphotericin B and Nystatin against Clinical Isolates of Coccidioides immitis at Various Saprobic Stages

2002 ◽  
Vol 46 (5) ◽  
pp. 1583-1585 ◽  
Author(s):  
Gloria M. González ◽  
Rolando Tijerina ◽  
Deanna A. Sutton ◽  
John R. Graybill ◽  
Michael G. Rinaldi
Keyword(s):  
Amphotericin B ◽  
Clinical Laboratory ◽  
National Committee ◽  
Growth Stages ◽  
Coccidioides Immitis ◽  
In Vitro Susceptibility ◽  
Broth Macrodilution ◽  
Lipid Formulations ◽  
Different Growth Stages

ABSTRACT We investigated the susceptibilities of hyphal, mixed hyphal, ungerminated arthroconidial, and germinated arthroconidial populations of Coccidioides immitis to lipid formulations of amphotericin B and nystatin and their conventional preparations, utilizing the National Committee for Clinical Laboratory Standards M38-P broth macrodilution method. The differences in effects of the three different growth stages of the saprobic phase of C. immitis on the MIC/minimum lethal concentration (MLC) ratio were not statistically significant for any of the antifungal agents tested. These results suggest that either inocula could be used for in vitro susceptibility studies with C. immitis.

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.

scholarly journals Trends in Antifungal Drug Susceptibility of Cryptococcus neoformans Isolates in the United States: 1992 to 1994 and 1996 to 1998

2001 ◽  
Vol 45 (11) ◽  
pp. 3065-3069 ◽  
Author(s):  
Mary E. Brandt ◽  
Michael A. Pfaller ◽  
Rana A. Hajjeh ◽  
Richard J. Hamill ◽  
Peter G. Pappas ◽  
...  
Keyword(s):  
Cryptococcus Neoformans ◽  
Amphotericin B ◽  
Antifungal Agents ◽  
Clinical Laboratory ◽  
The United States ◽  
Drug Susceptibility ◽  
Antifungal Drug ◽  
National Committee ◽  
Broth Microdilution Method

ABSTRACT The antifungal drug susceptibilities of two collections ofCryptococcus neoformans isolates obtained through active laboratory-based surveillance from 1992 to 1994 (368 isolates) and 1996 to 1998 (364 isolates) were determined. The MICs of fluconazole, itraconazole, and flucytosine were determined by the National Committee for Clinical Laboratory Standards broth microdilution method; amphotericin B MICs were determined by the E-test. Our results showed that the MIC ranges, the MICs at which 50% of isolates are inhibited (MIC50s), and the MIC90s of these four antifungal agents did not change from 1992 to 1998. In addition, very small numbers of isolates showed elevated MICs suggestive of in vitro resistance. The MICs of amphotericin B were elevated (≥2 μg/ml) for 2 isolates, and the MICs of flucytosine were elevated (≥32 μg/ml) for 14 isolates. Among the azoles, the fluconazole MIC was elevated (≥64 μg/ml) for 8 isolates and the itraconazole MIC (≥1 μg/ml) was elevated for 45 isolates. Analysis of 172 serial isolates from 71 patients showed little change in the fluconazole MIC over time. For isolates from 58 patients (82% of serial cases) there was either no change or a twofold change in the fluconazole MIC. In contrast, for isolates from seven patients (12% of serial cases) the increase in the MIC was at least fourfold. For isolates from another patient there was a 32-fold decrease in the fluconazole MIC over a 1-month period. We conclude that in vitro resistance to antifungal agents remains uncommon in C. neoformans and has not significantly changed with time during the past decade.

scholarly journals In vitro susceptibilities of clinical and environmental isolates of Cryptococcus neoformans to five antifungal drugs.

1996 ◽  
Vol 40 (3) ◽  
pp. 822-824 ◽  
Author(s):  
S P Franzot ◽  
J S Hamdan
Keyword(s):  
Cryptococcus Neoformans ◽  
Amphotericin B ◽  
Clinical Laboratory ◽  
Antifungal Drugs ◽  
Clinical Isolates ◽  
National Committee ◽  
Environmental Isolates ◽  
Susceptibility Data

A total of 53 Cryptococcus neoformans strains, including clinical and environmental Brazilian isolates, were tested for their susceptibilities to amphotericin B, 5-flucytosine, ketoconazole, fluconazole, and itraconazole. The tests were performed according to the National Committee of Clinical Laboratory Standards recommendations (document M27-P). In general, there was a remarkable homogeneity of results for all strains, and comparable MICs were found for environmental and clinical isolates. This paper represents the first contribution in which susceptibility data for Brazilian C. neoformans isolates are provided.

scholarly journals In Vitro Activity of A-192411.29, a Novel Antifungal Lipopeptide

2000 ◽  
Vol 44 (5) ◽  
pp. 1242-1246 ◽  
Author(s):  
Angela M. Nilius ◽  
Patti M. Raney ◽  
Dena M. Hensey-Rudloff ◽  
Weibo Wang ◽  
Qun Li ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Clinical Laboratory ◽  
Vitro Activity ◽  
National Committee ◽  
In Vitro Activity ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Structural Template ◽  
Better Than

ABSTRACT A-192411.29 is a novel antifungal agent derived from the structural template of the natural product echinocandin. The in vitro activity of A-192411.29 against common pathogenic yeasts was assessed by National Committee for Clinical Laboratory Standards method M27-A. It demonstrated broad-spectrum, fungicidal activity and was active against the most clinically relevant yeasts, such as Candida albicans, Candida tropicalis, and Candida glabrata, as well as less commonly encounteredCandida species; in general, its potency on a weight basis was comparable to that of amphotericin B. It maintained potent in vitro activity against Candida strains with reduced susceptibilities to fluconazole and amphotericin B. The in vitro activity of A-192411.29 against Cryptococcus neoformans was comparable to its activity against Candida spp. However, A-192411.29 did not demonstrate complete growth inhibition ofAspergillus fumigatus by the broth microdilution method used. A-192411.29 possesses an antifungal profile comparable to or better than those of fluconazole and amphotericin B against pathogenic yeasts, including strains resistant to fluconazole or amphotericin B, suggesting that it may be a therapeutically useful new antifungal drug.

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