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 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 Interactions between Triazoles and Amphotericin B against Cryptococcus neoformans

2000 ◽  
Vol 44 (9) ◽  
pp. 2435-2441 ◽  
Author(s):  
Francesco Barchiesi ◽  
Anna M. Schimizzi ◽  
Francesca Caselli ◽  
Andrea Novelli ◽  
Stefania Fallani ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Cryptococcus Neoformans ◽  
Amphotericin B ◽  
Clinical Laboratory ◽  
Fungal Infections ◽  
National Committee ◽  
Positive Interaction ◽  
Pronounced Increase

ABSTRACT The interaction of amphotericin B (AmB) and azole antifungal agents in the treatment of fungal infections is still a controversial issue. A checkerboard titration broth microdilution-based method that adhered to the recommendations of the National Committee for Clinical Laboratory Standards was applied to study the in vitro interactions of AmB with fluconazole (FLC), itraconazole (ITC), and the new investigational triazole SCH 56592 (SCH) against 15 clinical isolates ofCryptococcus neoformans. Synergy, defined as a fractional inhibitory concentration (FIC) index of ≤0.50, was observed for 7% of the isolates in studies of the interactions of both FLC-AmB and ITC-AmB and for 33% of the isolates in studies of the SCH-AmB interactions; additivism (FICs, >0.50 to 1.0) was observed for 67, 73, and 53% of the isolates in studies of the FLC-AmB, ITC-AmB, and SCH-AmB interactions, respectively; indifference (FICs, >1.0 to ≤2.0) was observed for 26, 20, and 14% of the isolates in studies of the FLC-AmB, ITC-AmB, and SCH-AmB interactions, respectively. Antagonism (FIC >2.0) was not observed. When synergy was not achieved, there was still a decrease, although not as dramatic, in the MIC of one or both drugs when they were used in combination. To investigate the effects of FLC-AmB combination therapy in vivo, we established an experimental model of systemic cryptococcosis in BALB/c mice by intravenous injection of cells of C. neoformans 2337, a clinical isolate belonging to serotype D against which the combination of FLC and AmB yielded an additive interaction in vitro. Both survival and tissue burden studies showed that combination therapy was more effective than FLC alone and that combination therapy was at least as effective as AmB given as a single drug. On the other hand, when cells of C. neoformans 2337 were grown in FLC-containing medium, a pronounced increase in resistance to subsequent exposures to AmB was observed. In particular, killing experiments conducted with nonreplicating cells showed that preexposure to FLC abolished the fungicidal activity of the polyene. However, this apparent antagonism was not observed in vivo. Rather, when the two drugs were used sequentially for the treatment of systemic murine cryptococcosis, a reciprocal potentiation was often observed. Our study shows that (i) the combination of triazoles and AmB is significantly more active than either drug alone against C. neoformans in vitro and (ii) the concomitant or sequential use of FLC and AmB for the treatment of systemic murine cryptococcosis results in a positive interaction.

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 Melanization of Cryptococcus neoformans and Histoplasma capsulatum Reduces Their Susceptibilities to Amphotericin B and Caspofungin

2002 ◽  
Vol 46 (11) ◽  
pp. 3394-3400 ◽  
Author(s):  
David van Duin ◽  
Arturo Casadevall ◽  
Joshua D. Nosanchuk
Keyword(s):  
Cryptococcus Neoformans ◽  
Amphotericin B ◽  
Fungal Pathogens ◽  
Histoplasma Capsulatum ◽  
Clinical Laboratory ◽  
National Committee ◽  
Broth Macrodilution ◽  
Mammalian Infection

ABSTRACT The fungal pathogens Cryptococcus neoformans and Histoplasma capsulatum produce melanin-like pigments in the presence of l-dopa in vitro and during mammalian infection. We investigated whether melanization affected the susceptibilities of the fungi to amphotericin B, caspofungin, fluconazole, itraconazole, or flucytosine (5FC). Using the standard macrodilution MIC protocol (the M27A protocol) of the National Committee for Clinical Laboratory Standards for yeast, we found no difference in the susceptibilities of melanized and nonmelanized C. neoformans and H. capsulatum isolates. Killing assays demonstrated that melanization reduced the susceptibilities of both fungi to amphotericin B and caspofungin. Laccase-deficient C. neoformans cells grown with l-dopa were significantly more susceptible than congenic melanin-producing yeast to killing by amphotericin B or caspofungin. Preincubation of amphotericin B or caspofungin with melanins decreased their antifungal activities. Elemental analysis of melanins incubated with amphotericin B or caspofungin revealed an alteration in the C:N ratios of the melanins, which indicated binding of these drugs by the melanins. In contrast, incubation of fluconazole, itraconazole, or 5FC with melanins did not significantly affect the antifungal efficacies of the drugs or the chemical composition of the melanins. The results suggest a potential explanation for the inefficacy of caspofungin against C. neoformans in vivo, despite activity in vitro. Furthermore, the results indicate that fungal melanins protect C. neoformans and H. capsulatum from the activities of amphotericin B and caspofungin and that this protection is not demonstrable by standard broth macrodilution assays.

scholarly journals In vitro susceptibility to antifungal agents of clinical and environmental Cryptococcus neoformans isolated in Southern of Brazil

2001 ◽  
Vol 43 (5) ◽  
pp. 267-270 ◽  
Author(s):  
Sydney Hartz ALVES ◽  
Loiva T. OLIVEIRA ◽  
Jane M. COSTA ◽  
Irina LUBECK ◽  
Agnes Kiesling CASALI ◽  
...  
Keyword(s):  
Cryptococcus Neoformans ◽  
Amphotericin B ◽  
Antifungal Agents ◽  
Susceptibility Testing ◽  
Clinical Isolates ◽  
Environmental Isolates ◽  
Aids Patients ◽  
In Vitro Susceptibility ◽  
Minimal Inhibitory Concentrations

The purpose of the present study was to compare the susceptibility to four antifungal agents of 69 Cryptococcus neoformans strains isolated from AIDS patients with that of 13 C. neoformans strains isolated from the environment. Based on the NCCLS M27-A methodology the Minimal Inhibitory Concentrations (MICs) obtained for amphotericin B, itraconazole and ketoconazole were very similar for clinical and environmental isolates. Clinical isolates were less susceptible to fluconazole than environmental isolates. The significance of these findings and aspects concerning the importance, role and difficulties of C. neoformans susceptibility testing are also discussed.

scholarly journals In Vitro Antifungal Susceptibility Of Griseofulvin, Fluconazole, Itraconazole And Terbinafine Against Clinical Isolates Of Trichophyton Rubrum And Trichophyton Mentagrophytes

2014 ◽  
Vol 2 (1) ◽  
Author(s):  
K R Reddy ◽  
S Ram Reddy
Keyword(s):  
Trichophyton Rubrum ◽  
Clinical Laboratory ◽  
Antifungal Susceptibility ◽  
Trichophyton Mentagrophytes ◽  
Drug Susceptibility ◽  
Antifungal Drugs ◽  
Clinical Isolates ◽  
National Committee ◽  
In Vitro Antifungal Susceptibility

Investigations on antifungal drug susceptibility were carried out on 90 clinical isolates of Trichophyton rubrum, and Trichophyton mentagrophytes with four antifungal drugs, namely griseofulvin, fluconazole, itraconazole and terbinafine as suggested by National Committee for Clinical Laboratory Standards (NCCLS) M27–A (1997) document by broth macrodilution method to standardize in vitro antifungal susceptibility testing and to find out the Minimum Inhibitory Concentration (MIC) of the drugs. In this study, terbinafine was found to be the most efficient drug for all isolates. Terbinafine had the lowest MIC range of 0.001 g/ml to 0.09 g/ml and MIC50 was low at 0.005 g/ml and MIC90 was also low at 0.04 g/ml against T.rubrum; and MIC range of 0.001μg/ml to 0.19μg/ml with a MIC50 of 0.01μg/ml and MIC90 at 0.09μg/ml against T.mentagrophytes. Itraconazole showed antifungal activity superior to that of fluconazole, with a MIC range of 0.04g/ml to 1.56g/ml, with MIC50 at 0.19μg/ml and MIC90 at 1.56g/ml against T.rubrum; and MIC range of 0.04μg/ml to 1.56μg/ml, with MIC50 at 0.19μg/ml and MIC90 at 0.78μg/ml against T.mentagrophytes. Griseofulvin appears to be still a potent drug for management of dermatophytoses. Griseofulvin had a MIC range of 0.15g/ml to 5.07 g/ml with MIC50 at1.26 g/ml and MIC90 at 2.53 g/ml against T.rubrum; and MIC range of 0.31μg/ml to 5.07μg/ml with MIC50 at 1.26μg/ml and MIC90 at 2.53μg/ml against T.mentagrophytes. Fluconazole showed a high MIC range of 0.19 g/ml to 50 g/ml and MIC50 was high at 1.56g/ml and MIC90 was also high at 12.5 g/ml against T.rubrum; and a high MIC range of 0.09μg/ml to 25.0μg/ml, with MIC50 at 1.56μg/ml and MIC90 at 12.5μg/ml towards T.mentagrophytes. The technique was found to be easy to perform and reliable with consistent results.

scholarly journals In Vitro Testing of Susceptibilities of Filamentous Ascomycetes to Voriconazole, Itraconazole, and Amphotericin B, with Consideration of Phylogenetic Implications

1998 ◽  
Vol 36 (8) ◽  
pp. 2353-2355 ◽  
Author(s):  
Michael R. McGinnis ◽  
Lester Pasarell
Keyword(s):  
Amphotericin B ◽  
Clinical Laboratory ◽  
Reference Method ◽  
Antifungal Drugs ◽  
National Committee ◽  
In Vitro Testing ◽  
Phylogenetic Relatedness ◽  
Phylogenetic Implications ◽  
The Family

The in vitro susceptibilities of three hundred eighty-one isolates representing two classes, five orders, nine families, 30 genera, and 51 species of ascomycetous fungi to voriconazole, itraconazole, and amphotericin B were tested by using a modification of the National Committee for Clinical Laboratory Standards M27-A reference method. For those fungi of known phylogenetic relatedness, drug MICs were consistently low for isolates among all clades, except for members of the family Microascaceae. The highest MICs of all drugs tested were consistently for the Microascaceae, supporting the observation of fungal phylogeny and corresponding susceptibility to antifungal drugs. Itraconazole and voriconazole have a broad range of activity against phylogenetically similar agents of hyalohyphomycosis, phaeohyphomycosis, chromoblastomycosis, and mycetoma.

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.

In vitro antifungal susceptibility of griseofulvin, fluconazole, itraconazole and terbinafine against clinical isolates of Trichophyton rubrum and Trichophyton mentagrophytes

2014 ◽  
Vol 1 (4) ◽  
pp. 26-28
Author(s):  
KR Reddy ◽  
SR Reddy
Keyword(s):  
Trichophyton Rubrum ◽  
Clinical Laboratory ◽  
Antifungal Susceptibility ◽  
Trichophyton Mentagrophytes ◽  
Drug Susceptibility ◽  
Antifungal Drugs ◽  
Clinical Isolates ◽  
National Committee ◽  
In Vitro Antifungal Susceptibility

Investigations on antifungal drug susceptibility were carried out on 90 clinical isolates of Trichophyton rubrum, and Trichophyton mentagrophytes with four antifungal drugs, namely griseofulvin, fluconazole, itraconazole and terbinafine as suggested by National Committee for Clinical Laboratory Standards (NCCLS) M27A (1997) document by broth macrodilution method to standardize in vitro antifungal susceptibility testing and to find out the Minimum Inhibitory Concentration (MIC) of the drugs. In this study, terbinafine was found to be the most efficient drug for all isolates. Terbinafine had the lowest MIC range of 0.001 g/mlto 0.09 g/ml and MIC50 was low at 0.005 g/ml and MIC90 was also low at 0.04 g/ml against T. rubrum; and MIC range of 0.001pg/ml to 0.19pg/ml with a MIC50 of 0.01pg/ml and MIC90 at 0.09 pg/ml against T. mentagrophytes. Itraconazole showed antifungal activity superior to that of fluconazole, with a MIC range of 0.04g/ml to l.56g/ml, with MIC50 at 0.19pg/m land MIC90 at l.56g/ml against T. rubrum; and MIC range of 0.04.g/ml to 1.56pg/ml, with MIC50 at 0.19pg/ml and MIC90 at 0.78pg/ml against T. mentagrophytes. Griseofulvin appears to be still a potent drug for management of dermatophytoses. Griseofulvin had a MIC range of 0.15g/ml to 5.07 g/ml with MIC50 at l.26 g/ml and MIC90 at 2.53 g/ml against T. rubrum; and MIC range of 0.31pg/ml to 5.07pg/ml with MIC50 at 1.26pg/ml and MIC90 at 2.53pg/ml against T. mentagrophytes. Fluconazole showed a high MIC range of 0.19 g/ml to 50 g/ml and MIC50 was high at 1.56g/ml and MIC90 was also high at 12.5 g/ml against T. rubrum; and a high MIC range of 0.09pg/ml to 25.0pg/ml, with MIC50 at 1.56pg/ml and MIC90 at 12.5pg/ml towards T. mentagrophytes. The technique was found to be easy to perform and reliable with consistent results.DOI: http://dx.doi.org/10.3126/jucms.v1i4.9569 Journal of Universal College of Medical Sciences (2013) Vol.1 No.04: 26-28

scholarly journals Comparative Evaluation of FUNGITEST and Broth Microdilution Methods for Antifungal Drug Susceptibility Testing of Candida Species and Cryptococcus neoformans

1998 ◽  
Vol 36 (4) ◽  
pp. 926-930 ◽  
Author(s):  
Kate G. Davey ◽  
Ann D. Holmes ◽  
Elizabeth M. Johnson ◽  
Adrien Szekely ◽  
David W. Warnock
Keyword(s):  
Cryptococcus Neoformans ◽  
Amphotericin B ◽  
Susceptibility Testing ◽  
Clinical Laboratory ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
National Committee ◽  
Broth Microdilution ◽  
Fluconazole Resistant

The FUNGITEST method (Sanofi Diagnostics Pasteur, Paris, France) is a microplate-based procedure for the breakpoint testing of six antifungal agents (amphotericin B, flucytosine, fluconazole, itraconazole, ketoconazole, and miconazole). We compared the FUNGITEST method with a broth microdilution test, performed according to National Committee for Clinical Laboratory Standards document M27-A guidelines, for determining the in vitro susceptibilities of 180 isolates ofCandida spp. (50 C. albicans, 50C. glabrata, 10 C. kefyr, 20C. krusei, 10 C. lusitaniae, 20C. parapsilosis, and 20 C. tropicalisisolates) and 20 isolates of Cryptococcus neoformans. Overall, there was 100% agreement between the methods for amphotericin B, 95% agreement for flucytosine, 84% agreement for miconazole, 83% agreement for itraconazole, 77% agreement for ketoconazole, and 76% agreement for fluconazole. The overall agreement between the methods exceeded 80% for all species tested with the exception ofC. glabrata (71% agreement). The poorest agreement between the results for individual agents was seen with C. glabrata (38% for fluconazole, 44% for ketoconazole, and 56% for itraconazole) and C. tropicalis (50% for miconazole). The FUNGITEST method misclassified as susceptible 2 of 12 (16.6%) fluconazole-resistant isolates, 2 of 10 (20%) itraconazole-resistant isolates, and 4 of 8 (50%) ketoconazole-resistant isolates of several Candida spp. Further development of the FUNGITEST procedure will be required before it can be recommended as an alternative method for the susceptibility testing of Candida spp. or C. neoformans.

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