scholarly journals In Vitro Comparison of Terbinafine and Itraconazole against Penicillium marneffei

2000 ◽  
Vol 44 (5) ◽  
pp. 1407-1408 ◽  
Author(s):  
Michael R. McGinnis ◽  
Nicole G. Nordoff ◽  
Neil S. Ryder ◽  
Gary B. Nunn
Keyword(s):  
Clinical Laboratory ◽  
Geometric Mean ◽  
Penicillium Marneffei ◽  
National Committee ◽  
Geometric Mean Titer ◽  
Broth Macrodilution ◽  
Glucose Agar ◽  
Sabouraud Glucose Agar ◽  
Drug Dilution

ABSTRACT We evaluated terbinafine and itraconazole against 30 isolates ofPenicillium marneffei using a modification of the National Committee for Clinical Laboratory Standards broth macrodilution MIC testing protocol for yeasts. The minimal fungicidal concentration (MFC) was determined by plating 100 μl from each MIC drug dilution having no growth onto Sabouraud glucose agar incubated at 30°C. The MFC was the dilution at which growth was absent at 72 h of incubation. The MICs, in micrograms per milliliter, were as follows: terbinafine, 0.03 to 1.0 (geometric mean titer, 0.09); itraconazole, 0.03 to 0.5 (geometric mean titer, 0.04). The MFCs, in micrograms per milliliter, were as follows: terbinafine, 0.03 to 8 (geometric mean titer, 2.60); itraconazole, 0.03 to 8 (geometric mean titer, 2.45). Primary fungicidal activity (MFC within 2 dilutions of MIC) was observed with terbinafine in eight isolates and with itraconazole in four isolates. The data indicate that terbinafine is active against P. marneffei in vitro and may have a previously unrealized role in the management of infections caused by this fungus.

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 Fluconazole Susceptibilities of Bloodstream Candidasp. Isolates as Determined by National Committee for Clinical Laboratory Standards Method M27-A and Two Other Methods

1999 ◽  
Vol 37 (7) ◽  
pp. 2197-2200 ◽  
Author(s):  
Emilia Cantón ◽  
Javier Pemán ◽  
Alfonso Carrillo-Muñoz ◽  
Ana Orero ◽  
Pedro Ubeda ◽  
...  
Keyword(s):  
Clinical Laboratory ◽  
Geometric Mean ◽  
Inhibition Zone ◽  
Diffusion Method ◽  
National Committee ◽  
Dilution Method ◽  
Inhibition Zone Diameter ◽  
Zone Diameter ◽  
The Mean

The in vitro activity of fluconazole against 143Candida spp. obtained from the bloodstreams of 143 hospitalized patients from 1995 to 1997 was studied. Susceptibility tests were carried out by two macrodilution methods, the M27-A and a modified M27-A method (0.165 M, pH 7/morpholinepropanesulfonic acid-buffered RPMI 1640 medium supplemented with 20 g ofd-dextrose per liter), and by the agar diffusion method (with 15-μg fluconazole [Neo-Sensitab] tablets). With 2 μg of fluconazole per ml, 96.92% of 65 C. albicans isolates, 86.2% of 58 C. parapsilosis isolates 7 of 8 C. tropicalis isolates, and 1 of 6 C. glabrata isolates were inhibited. Only one strain of C. albicans and one strain of C. tropicalis were resistant. The agreement between the two macrodilution methods was greater than 90% within ±2 log2 dilutions for all strains except C. glabrata (83.3%) and C. tropicalis(87.5%). Generally, MICs were 1 log2 dilution lower in glucose-supplemented RPMI 1640 medium. No correlation between zone sizes and MICs was found. All strains susceptible by the diffusion test were susceptible by the dilution method, but the converse was not necessarily true. Interestingly, inhibition zones were smaller forC. albicans, for which the geometric mean MIC was 0.29 μg/ml and the mean inhibition zone diameter was 25.7 mm, while for C. parapsilosis the geometric mean MIC was 0.96 μg/ml and the mean inhibition zone diameter was 31.52 mm. In conclusion, the two macrodilution methods give similar results. The modified M27-A method with 2% dextrose has the advantage of shortening the incubation time and simplifying the endpoint determination.

In vitro studies of activities of the antifungal triazoles SCH56592 and itraconazole against Candida albicans, Cryptococcus neoformans, and other pathogenic yeasts.

1997 ◽  
Vol 41 (1) ◽  
pp. 180-183 ◽  
Author(s):  
J N Galgiani ◽  
M L Lewis
Keyword(s):  
Incubation Temperature ◽  
Clinical Laboratory ◽  
Synthetic Medium ◽  
Reference Method ◽  
Inoculum Size ◽  
Antifungal Drugs ◽  
Yeast Cells ◽  
National Committee ◽  
Broth Macrodilution

We investigated the effects of various assay conditions on the activities of two antifungal drugs, SCH56592 and itraconazole, against seven species of fungi by the broth macrodilution testing procedure proposed by the National Committee for Clinical Laboratory Standards (NCCLS). For both drugs, which are insoluble in water, the concentration and type of solubilizing agent produced differences in drug activity. Starting inoculum size differences from 10(2) to 10(5) yeast cells per ml resulted in approximately a fourfold effect on the MIC of both drugs, but other significant differences were not observed with variations in synthetic medium composition, pH, buffering reagent, or incubation temperature. Under standardized conditions of reference method M27-T with 1% polyethylene glycol as the solubilizing agent, median MICs of SCH56592 and itraconazole of 60 and 125 mg/ml, respectively, were demonstrated for 110 strains (12 to 23 strains for each of seven species). Broth microdilution results were typically severalfold higher than broth macrodilution results. We conclude that the NCCLS standard reference method can be applied without modification to the testing of SCH56592 and itraconazole, but particular attention to solubilizing the agents is critical to obtaining consistent results.

scholarly journals In Vitro Activity of a New Oral Triazole, BMS-207147 (ER-30346)

1998 ◽  
Vol 42 (2) ◽  
pp. 313-318 ◽  
Author(s):  
Joan C. Fung-Tomc ◽  
Elizabeth Huczko ◽  
Beatrice Minassian ◽  
Daniel P. Bonner
Keyword(s):  
Filamentous Fungi ◽  
Clinical Laboratory ◽  
Sporothrix Schenckii ◽  
Fungal Species ◽  
National Committee ◽  
Microsporum Gypseum ◽  
Dematiaceous Fungi ◽  
Pseudallescheria Boydii ◽  
Broth Macrodilution

ABSTRACT The antifungal activity of BMS-207147 (also known as ER-30346) was compared to those of itraconazole and fluconazole against 250 strains of fungi representing 44 fungal species. MICs were determined by using the National Committee for Clinical Laboratory Standards (NCCLS)-recommended broth macrodilution method for yeasts, which was modified for filamentous fungi. BMS-207147 was about two- to fourfold more potent than itraconazole and about 40-fold more active than fluconazole against yeasts. With the NCCLS-recommended resistant MIC breakpoints of ≥1 μg/ml for itraconazole and of ≥64 μg/ml for fluconazole against Candida spp., itraconazole and fluconazole were inactive against strains of Candida kruseiand Candida tropicalis. In contrast, all but 9 (allC. tropicalis) of the 116 Candida strains tested had BMS-207147 MICs of <1 μg/ml. The three triazoles were active against about half of the Candida glabrata strains and against all of the Cryptococcus neoformans strains tested. The three triazoles were fungistatic to most yeast species, except for BMS-207147 and itraconazole, which were fungicidal to cryptococci. BMS-207147 and itraconazole were inhibitory to most aspergilli, and against half of the isolates, the activity was cidal. BMS-207147 and itraconazole were active, though not cidal, against most hyaline Hyphomycetes (with the exception ofFusarium spp. and Pseudallescheria boydii), dermatophytes, and the dematiaceous fungi and inactive againstSporothrix schenckii and zygomycetes. Fluconazole, on the other hand, was inactive against most filamentous fungi with the exception of dermatophytes other than Microsporum gypseum. Thus, the spectrum and potency of BMS-207147 indicate that it should be a candidate for clinical development.

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 Comparison of the in vitro activities of the echinocandin LY303366, the pneumocandin MK-0991, and fluconazole against Candida species and Cryptococcus neoformans.

1997 ◽  
Vol 41 (9) ◽  
pp. 1957-1960 ◽  
Author(s):  
T V Krishnarao ◽  
J N Galgiani
Keyword(s):  
Cryptococcus Neoformans ◽  
Candida Species ◽  
Clinical Laboratory ◽  
Inoculum Size ◽  
National Committee ◽  
Broth Microdilution ◽  
Test Conditions ◽  
Broth Macrodilution ◽  
Glucan Synthesis

Two new glucan synthesis inhibitors, the echinocandin LY303366 and the pneumocandin MK-0991 (formerly L-743,872), were studied for their antifungal activities in vitro in relation to each other and in relation to the activity of the triazole fluconazole. Systematic analysis of broth macrodilution testing by varying the starting inoculum size, medium composition, medium pH, temperature of incubation, length of incubation, or selection of endpoints failed to identify significant differences in antifungal activity for either LY303366 or MK-0991 in comparison to the activity under standard test conditions specified for other antifungal agents in National Committee for Clinical Laboratory Standards (NCCLS) document M27A. Under standardized conditions, both drugs exhibited prominent activity against Candida species including Candida glabrata and Candida krusei but showed little activity against Cryptococcus neoformans. This spectrum of activity differed from that of fluconazole, which exhibited marginal activity against C. glabrata and C. krusei but prominent activity against other Candida species and C. neoformans. For individual strains, broth microdilution MICs of LY303366 and MK-0991 were similar to but frequently higher than broth macrodilution results. In contrast, fluconazole broth microdilution MICs were often lower than broth microdilution results. We conclude that the test conditions specified in NCCLS document M27A are applicable to these two new glucan synthesis inhibitors and that systematic differences between broth microdilution procedures and the broth macrodilution reference standard will need to be addressed before the two test methods can be used interchangeably.

scholarly journals Evaluation of a flow cytofluorometric method for rapid determination of amphotericin B susceptibility of yeast isolates.

1997 ◽  
Vol 41 (7) ◽  
pp. 1537-1540 ◽  
Author(s):  
F Peyron ◽  
A Favel ◽  
H Guiraud-Dauriac ◽  
M El Mzibri ◽  
C Chastin ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Fluorescence Intensity ◽  
Clinical Laboratory ◽  
Rapid Determination ◽  
Reference Method ◽  
National Committee ◽  
Candida Spp ◽  
Broth Macrodilution

A rapid-flow cytofluorometric susceptibility test for in vitro amphotericin B testing of yeasts was evaluated and compared to the National Committee for Clinical Laboratory Standards (NCCLS) M27-T reference broth macrodilution method. The flow cytofluorometric method is based on the detection of decreased green fluorescence intensity of cells stained with DiOC5(3), a membrane potential-sensitive cationic dye, after drug treatment. Testing was performed on 134 clinical isolates (Candida spp. and Torulopsis glabrata). From the dose-response curve obtained for each isolate, three endpoints were calculated by computer analysis (the concentrations at which the fluorescence intensity was reduced by 50, 80, and 90%, i.e., 50% inhibitory concentration [IC50], IC80, and IC90, respectively). A regression analysis correlating these endpoints with the M27-T MICs showed that the best agreement was obtained with IC80. The flow cytofluorometric method showed good reproducibility with control strains. These initial results suggest that the flow cytofluorometric method is a valid alternative to the NCCLS reference method.

scholarly journals In Vitro Synergistic Interaction between Amphotericin B and Pentamidine against Scedosporium prolificans

2002 ◽  
Vol 46 (10) ◽  
pp. 3323-3326 ◽  
Author(s):  
Javier Afeltra ◽  
Eric Dannaoui ◽  
Jacques F. G. M. Meis ◽  
Juan L. Rodriguez-Tudela ◽  
Paul E. Verweij
Keyword(s):  
Response Surface ◽  
Amphotericin B ◽  
Clinical Laboratory ◽  
Geometric Mean ◽  
Surface Modeling ◽  
National Committee ◽  
Response Surface Modeling ◽  
Microdilution Method ◽  
Scedosporium Prolificans

ABSTRACT To develop new approaches for the treatment of invasive infections caused by Scedosporium prolificans, the in vitro interaction between amphotericin B and pentamidine against 30 clinical isolates was evaluated using a checkerboard microdilution method based on the National Committee for Clinical Laboratory Standards M38-P guidelines. The interaction between the drugs was analyzed using fractional inhibitory concentration index (FICI) analysis and response surface modeling. Amphotericin B alone was inactive against all the isolates. The geometric mean MIC for pentamidine was 57 μg/ml (range, 8 to 256 μg/ml; MIC at which 50% of the isolates tested were inhibited [MIC50], 64 μg/ml; MIC90, 128 μg/ml). The combination was synergistic against 28 of 30 isolates (93.3%) by FICI analysis and 30 of 30 (100%) by response surface modeling analysis. Antagonism was not observed.

scholarly journals In Vitro Activity of Levofloxacin against a Selected Group of Anaerobic Bacteria Isolated from Skin and Soft Tissue Infections

1998 ◽  
Vol 42 (4) ◽  
pp. 984-986 ◽  
Author(s):  
Hannah M. Wexler ◽  
Eric Molitoris ◽  
Denise Molitoris ◽  
Sydney M. Finegold
Keyword(s):  
Soft Tissue ◽  
Clinical Laboratory ◽  
Geometric Mean ◽  
Anaerobic Bacteria ◽  
Vitro Activity ◽  
National Committee ◽  
Soft Tissue Infections ◽  
In Vitro Activity ◽  
Select Group

ABSTRACT The in vitro activity of levofloxacin was compared to the activities of ofloxacin, ciprofloxacin, ampicillin-sulbactam (2:1), cefoxitin, and metronidazole for a selected group of anaerobes (n = 175) isolated from skin and soft tissue infections by using the National Committee for Clinical Laboratory Standards-approved Wadsworth method. Ampicillin-sulbactam and cefoxitin inhibited 99% of the strains of this select group, levofloxacin and ofloxacin inhibited 73 and 50%, respectively, at 2 μg/ml, and ciprofloxacin inhibited 51% at 1 μg/ml. The geometric mean MIC of levofloxacin was lower than those of ofloxacin and ciprofloxacin for every group except Veillonella.

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