scholarly journals In Vitro Antifungal Activities of Bis(Alkylpyridinium)Alkane Compounds against Pathogenic Yeasts and Molds

2010 ◽  
Vol 54 (8) ◽  
pp. 3233-3240 ◽  
Author(s):  
Sharon C.-A. Chen ◽  
Chayanika Biswas ◽  
Robyn Bartley ◽  
Fred Widmer ◽  
Namfon Pantarat ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Candida Glabrata ◽  
Fungicidal Activity ◽  
Candida Parapsilosis ◽  
Clinical Laboratory ◽  
Geometric Mean ◽  
Candida Guilliermondii ◽  
Antifungal Activities ◽  
Yeasts And Molds

ABSTRACT Ten bis(alkylpyridinium)alkane compounds were tested for antifungal activity against 19 species (26 isolates) of yeasts and molds. We then determined the MICs and minimum fungicidal concentrations (MFCs) of four of the most active compounds (compounds 1, 4, 5, and 8) against 80 Candida and 20 cryptococcal isolates, in comparison with the MICs of amphotericin B, fluconazole, itraconazole, voriconazole, posaconazole, and caspofungin, using Clinical Laboratory and Standards Institutes broth microdulition M27-A3 (yeasts) or M38-A2 (filamentous fungi) susceptibility protocols. The compounds were more potent against Candida and Cryptococcus spp. (MIC range, 0.74 to 27.9 μg/ml) than molds (0.74 to 59.7 μg/ml). MICs against Exophiala were 0.37 to 5.9 μg/ml and as low as 1.48 μg/ml for Scedosporium but ≥25 μg/ml for zygomycetes, Aspergillus, and Fusarium spp. Compounds 1, 4, 5, and 8 exhibited good fungicidal activity against Candida and Cryptococcus, except for Candida parapsilosis (MICs of >44 μg/ml). Geometric mean (GM) MICs were similar to those of amphotericin B and lower than or comparable to fluconazole GM MICs but 10- to 100-fold greater than those for the other azoles. GM MICs against Candida glabrata were <1 μg/ml, significantly lower than fluconazole GM MICs (P < 0.001) and similar to those of itraconazole, posaconazole, and voriconazole (GM MIC range of 0.4 to 1.23 μg/ml). The GM MIC of compound 4 against Candida guilliermondii was lower than that of fluconazole (1.69 μg/ml versus 7.48 μg/ml; P = 0.012). MICs against Cryptococcus neoformans and Cryptococcus gattii were similar to those of fluconazole. The GM MIC of compound 4 was significantly higher for C. neoformans (3.83 μg/ml versus 1.81 μg/ml for C. gattii; P = 0.015). This study has identified clinically relevant in vitro antifungal activities of novel bisalkypyridinium alkane compounds.

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

1997 ◽  
Vol 41 (4) ◽  
pp. 763-766 ◽  
Author(s):  
M A Pfaller ◽  
S A Messer ◽  
S Coffman
Keyword(s):  
Amphotericin B ◽  
Fungicidal Activity ◽  
Antifungal Agents ◽  
Candida Parapsilosis ◽  
Clinical Laboratory ◽  
National Committee ◽  
In Vitro Activity ◽  
Medical Centers

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.

scholarly journals Aspectos micológicos e suscetibilidade in vitro de leveduras do gênero Candida em pacientes HIV-positivos provenientes do Estado de Mato Grosso

2010 ◽  
Vol 43 (6) ◽  
pp. 673-677 ◽  
Author(s):  
Olivia Cometti Favalessa ◽  
Marilena dos Anjos Martins ◽  
Rosane Christine Hahn
Keyword(s):  
Candida Albicans ◽  
Candida Tropicalis ◽  
Candida Glabrata ◽  
Candida Parapsilosis ◽  
Candida Guilliermondii ◽  
Candida Krusei ◽  
Mato Grosso ◽  
Candida Sp

INTRODUÇÃO: A candidíase é uma das infecções fúngicas mais frequentes entre os pacientes infectados pelo vírus da imunodeficiência humana. O presente estudo objetivou a caracterização das leveduras do gênero Candida de distintas amostras clínicas, provenientes de pacientes HIV - positivos, assim como a determinação do perfil de suscetibilidade in vitro a cinco drogas antifúngicas. MÉTODOS: A caracterização dos isolados de Candida sp foi realizada através da metodologia clássica, testes bioquímicos (zimograma e auxanograma) e morfológicos (prova do tubo germinativo e microcultivo em lâmina). Também, foram realizadas a técnica genotípica (PCR) e identificação pelo método comercial API 20C AUX (BioMeriéux). Para a determinação do perfil de suscetibilidade in vitro, foram utilizadas cinco drogas antifúngicas (cetoconazol, fluconazol, itraconazol, voriconazol e anfotericina B), através do método comercialmente disponível - Etest. RESULTADOS: Foram identificados 105 isolados de leveduras do gênero Candida provenientes de 102 pacientes infectados pelo vírus HIV. Destes, foram caracterizadas 82 (78,1%) Candida albicans, 8 (7,6%) Candida parapsilosis, 8 (7,6%) Candida tropicalis, 4 (3,8%) Candida krusei, 2 (1,9%) Candida glabrata e 1 (1%) Candida guilliermondii. CONCLUSÕES: Considerando o perfil geral de sensibilidade, 60% dos isolados foram suscetíveis a todos os antifúngicos testados, porém as espécies C. tropicalis e C. krusei demonstraram uma tendência a valores mais elevados de CIMs para os azóis do que os encontrados paraC. albicans, sugerindo resistência.

scholarly journals In Vitro Activity of a New Polyene, SPA-S-843, against Yeasts

1998 ◽  
Vol 42 (11) ◽  
pp. 3012-3013 ◽  
Author(s):  
C. Rimaroli ◽  
T. Bruzzese
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Candida Tropicalis ◽  
Candida Glabrata ◽  
Fungicidal Activity ◽  
Candida Krusei ◽  
Water Soluble ◽  
Vitro Activity ◽  
In Vitro Activity

ABSTRACT The in vitro activity of a new water-soluble polyene, SPA-S-843, was evaluated against 116 strains of Candida,Cryptococcus, and Saccharomyces spp. and compared with that of amphotericin B. SPA-S-843 demonstrated better inhibitory activity against all of the yeasts examined and better fungicidal activity against Candida albicans, Candida glabrata, Candida krusei, and Candida tropicalis than did amphotericin B.

In vitro and in vivo antifungal activities of ER-30346, a novel oral triazole with a broad antifungal spectrum.

1996 ◽  
Vol 40 (10) ◽  
pp. 2237-2242 ◽  
Author(s):  
K Hata ◽  
J Kimura ◽  
H Miki ◽  
T Toyosawa ◽  
T Nakamura ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Candida Glabrata ◽  
Candida Parapsilosis ◽  
Good Activity ◽  
Time Curve ◽  
Concentration Time ◽  
Wide Range ◽  
Systemic Infections

ER-30346 is a novel oral triazole with a broad spectrum of potent activity against a wide range of fungi. ER-30346, with MICs at which 90% of the strains tested are inhibited (MIC90s) ranging from 0.025 to 0.78 microgram/ml, was 4 to 32 times more active than itraconazole, fluconazole, and amphotericin B against Candida albicans, Candida parapsilosis, and Candida glabrata. Against Candida tropicalis, ER-30346, with an MIC90 of 12.5 micrograms/ml, was 2 to > 8 times more active than itraconazole and fluconazole, but was 16 times less active than amphotericin B. ER-30346 (MIC90, 0.78 microgram/ml) was four to eight times more active than fluconazole and amphotericin B and had activity comparable to that of itraconazole against Trichosporon beigelli. The MIC90s of ER-30346 were 0.10 microgram/ml for Cryptococcus neoformans and 0.39 microgram/ml for Aspergillus fumigatus. ER-30346 was 2 to 8 times more active than itraconazole and amphotericin B and 32 to > 256 times more active than fluconazole. ER-30346 also showed good activity against dermatophytes, with MICs ranging from 0.05 to 0.39 microgram/ml, and its activity was comparable to or 2 to 16 times higher than those of itraconazole and amphotericin B and > 32 times higher than that of fluconazole. In vivo activity was evaluated with systemic infections in mice. Against systemic candidiasis and cryptococcosis, ER-30346 was comparable in efficacy to fluconazole and was more effective than itraconazole. Of the drugs tested, ER-30346 was the most effective drug against systemic aspergillosis. We studied the levels of ER-30346 in mouse plasma. The maximum concentration of drug in plasma and the area under the concentration-time curve for ER-30346 showed good linearity over a range of doses from 2 to 40 mg/kg of body weight.

Antifungal activity and killing kinetics of anidulafungin, caspofungin and amphotericin B against Candida auris

2019 ◽  
Vol 74 (8) ◽  
pp. 2295-2302 ◽  
Author(s):  
Catiana Dudiuk ◽  
Indira Berrio ◽  
Florencia Leonardelli ◽  
Soraya Morales-Lopez ◽  
Laura Theill ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Fungicidal Activity ◽  
Geometric Mean ◽  
Candida Auris ◽  
Initial Inoculum ◽  
Concentration Maximum ◽  
High Concentrations ◽  
Time Kill ◽  
Kinetics Of

AbstractBackgroundCandida auris is an emerging MDR pathogen. It shows reduced susceptibility to azole drugs and, in some strains, high amphotericin B MICs have been described. For these reasons, echinocandins were proposed as first-line treatment for C. auris infections. However, information on how echinocandins and amphotericin B act against this species is lacking.ObjectivesOur aim was to establish the killing kinetics of anidulafungin, caspofungin and amphotericin B against C. auris by time–kill methodology and to determine if these antifungals behave as fungicidal or fungistatic agents against this species.MethodsThe susceptibility of 50 C. auris strains was studied. Nine strains were selected (based on echinocandin MICs) to be further studied. Minimal fungicidal concentrations, in vitro dose–response and time–kill patterns were determined.ResultsEchinocandins showed lower MIC values than amphotericin B (geometric mean of 0.12 and 0.94 mg/L, respectively). Anidulafungin and caspofungin showed no fungicidal activity at any concentration (maximum log decreases in cfu/mL between 1.34 and 2.22). On the other hand, amphotericin B showed fungicidal activity, but at high concentrations (≥2.00 mg/L). In addition, the tested polyene was faster than echinocandins at killing 50% of the initial inoculum (0.92 versus >8.00 h, respectively).ConclusionsAmphotericin B was the only agent regarded as fungicidal against C. auris. Moreover, C. auris should be considered tolerant to caspofungin and anidulafungin considering that their MFC:MIC ratios were mostly ≥32 and that after 6 h of incubation the starting inoculum was not reduced in >90%.

Enhancement of the in vitro activity of amphotericin B against the biofilms of non-albicans Candida spp. by rifampicin and doxycycline

2007 ◽  
Vol 56 (5) ◽  
pp. 645-649 ◽  
Author(s):  
Mohamed El-Azizi
Keyword(s):  
Amphotericin B ◽  
Antifungal Agent ◽  
Candida Glabrata ◽  
Candida Parapsilosis ◽  
Candida Krusei ◽  
In Vitro Activity ◽  
Candida Spp ◽  
Killing Activity

The in vitro activity of amphotericin B (AMB) alone and in combination with rifampicin (RIF) and doxycycline (DOX) was tested against the biofilms of 30 clinical isolates of non-albicans Candida (NAC) species namely, Candida parapsilosis, Candida krusei and Candida glabrata. The killing activity of AMB at 10×MIC was significantly increased in combination with either antibiotic. With RIF, the killing activity increased by 20.6, 23.5 and 14 % against the biofilms of C. parapsilosis, C. krusei and C. glabrata, respectively; with DOX, the killing activity increased by 30.64, 35.28 and 31.13 %, respectively. Pre-exposure of the isolates to the same combinations significantly reduced the number of colonized cells in the biofilms by 20, 25.14 and 13.07 % with RIF for C. parapsilosis, C. krusei and C. glabrata, respectively, and by 18.94, 24.52 and 29.15 % with DOX, respectively. The data showed that combination of RIF or DOX with AMB enhanced the killing activity of the antifungal agent against biofilms of NAC species. Whether such an effect operates against biofilm-associated infections needs to be clarified by further in vivo studies.

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 Comparative In Vitro Activities of Caspofungin and Micafungin, Determined Using the Method of the European Committee on Antimicrobial Susceptibility Testing, against Yeast Isolates Obtained in France in 2005-2006

2007 ◽  
Vol 52 (2) ◽  
pp. 778-781 ◽  
Author(s):  
E. Dannaoui ◽  
O. Lortholary ◽  
D. Raoux ◽  
M. E. Bougnoux ◽  
G. Galeazzi ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Antimicrobial Susceptibility ◽  
Candida Glabrata ◽  
Candida Parapsilosis ◽  
Susceptibility Testing ◽  
Candida Guilliermondii ◽  
Candida Krusei ◽  
Clear Correlation ◽  
European Committee

ABSTRACT The in vitro activities of caspofungin and micafungin against 1,038 yeast isolates have been determined. The caspofungin and micafungin MICs were lower for Candida albicans, Candida glabrata, and Candida tropicalis than for Candida parapsilosis, Candida guilliermondii, and Candida krusei. A clear correlation was seen between the MICs for the two drugs.

scholarly journals Voriconazole-Induced Inhibition of the Fungicidal Activity of Amphotericin B inCandidaStrains with Reduced Susceptibility to Voriconazole: an Effect Not Predicted by the MIC Value Alone

2011 ◽  
Vol 55 (4) ◽  
pp. 1629-1637 ◽  
Author(s):  
Anders Lignell ◽  
Elisabeth Löwdin ◽  
Otto Cars ◽  
Dominique Sanglard ◽  
Jan Sjölin
Keyword(s):  
Amphotericin B ◽  
Candida Glabrata ◽  
Fungicidal Activity ◽  
Antagonistic Effect ◽  
Candida Krusei ◽  
Mechanisms Of Resistance ◽  
Dependent Inhibition ◽  
Resistant Strains ◽  
Mic Value

ABSTRACTAn antagonistic effect of voriconazole on the fungicidal activity of sequential doses of amphotericin B has previously been demonstrated inCandida albicansstrains susceptible to voriconazole. Because treatment failure and the need to switch to other antifungals are expected to occur more often in infections that are caused by resistant strains, it was of interest to study whether the antagonistic effect was still seen inCandidastrains with reduced susceptibility to voriconazole. With the hypothesis that antagonism will not occur in voriconazole-resistant strains,C. albicansstrains with characterized mechanisms of resistance against voriconazole, as well asCandida glabrataandCandida kruseistrains with differences in their degrees of susceptibility to voriconazole were exposed to voriconazole or amphotericin B alone, to both drugs simultaneously, or to voriconazole followed by amphotericin B in anin vitrokinetic model. Amphotericin B administered alone or simultaneously with voriconazole resulted in fungicidal activity. When amphotericin B was administered after voriconazole, its activity was reduced (median reduction, 61%; range, 9 to 94%). Levels of voriconazole-dependent inhibition of amphotericin B activity differed significantly among the strains but were not correlated with the MIC values (correlation coefficient, −0.19;P= 0.65). Inhibition was found inC. albicansstrains with increases inCDR1andCDR2expression but not in the strain with an increase inMDR1expression. In summary, decreased susceptibility to voriconazole does not abolish voriconazole-dependent inhibition of the fungicidal activity of amphotericin B in voriconazole-resistantCandidastrains. The degree of interaction could not be predicted by the MIC value alone.

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