scholarly journals New sulfone and sulfanyl derivatives with antifungal activity

2018 ◽  
pp. 175-184
Author(s):  
Małgorzata Gizińska ◽  
Marzena Połaska ◽  
Zbigniew Ochal ◽  
Monika Staniszewska
Keyword(s):  
Antifungal Agents ◽  
Fungal Infections ◽  
In Vitro Susceptibility ◽  
Microdilution Method ◽  
Alternative Approach ◽  
Broth Microdilution Method ◽  
Fungal Morphogenesis ◽  
In Vitro Susceptibility Testing ◽  
Base Structure

Introduction: Increasing occurrence of fungal infections raises the need to develop novel antifungal agents. In this context, an inhibition of morphological switch may provide an alternative approach to find compounds with a potential to control the Candida albicans infections. Methods: A series of 17 sulfone and sulfanyl derivatives was synthesized and evaluated for activity against the C. albicans wild type (SC5314, ATCC) and SAP-deficient mutant strains using the broth microdilution method M27-A3. Afterwards, phase-contrast microscopy was applied to evaluate the inhibition of fungal morphogenesis under the influence of randomly selected active compounds: 1, 5 and 6. Results: By in vitro susceptibility testing of C. albicans, we identified the effective antifungal agents displaying moderate-to-good activity. Newly synthesized sulfanyl and sulfone derivatives strongly inhibited the C. albicans morphogenetic transition under the hyphae inducing conditions. Conclusions: The leading compound 6 has the potential to be used as a base structure in antifungal drug development, however further structural optimalization and toxicity studies are required.

scholarly journals In vitro susceptibility testing of dermatophytes isolated in Goiania, Brazil, against five antifungal agents by broth microdilution method

2009 ◽  
Vol 51 (1) ◽  
pp. 9-12 ◽  
Author(s):  
Crystiane Rodrigues Araújo ◽  
Karla Carvalho Miranda ◽  
Orionalda de Fatima Lisboa Fernandes ◽  
Ailton José Soares ◽  
Maria do Rosário Rodrigues Silva
Keyword(s):  
Antifungal Agents ◽  
Trichophyton Mentagrophytes ◽  
Microsporum Canis ◽  
Broth Microdilution ◽  
In Vitro Susceptibility ◽  
Microtiter Plates ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
In Vitro Susceptibility Testing

The antifungal activities of fluconazole, itraconazole, ketoconazole, terbinafine and griseofulvin were tested by broth microdilution technique, against 60 dermatophytes isolated from nail or skin specimens from Goiania city patients, Brazil. In this study, the microtiter plates were incubated at 28 ºC allowing a reading of the minimal inhibitory concentration (MIC) after four days of incubation for Trichophyton mentagrophytes and five days for T. rubrum and Microsporum canis. Most of the dermatophytes had uniform patterns of susceptibility to the antifungal agents tested. Low MIC values as 0.03 µg/mL were found for 33.3%, 31.6% and 15% of isolates for itraconazole, ketoconazole and terbinafine, respectively.

scholarly journals Current and Emerging Azole Antifungal Agents

1999 ◽  
Vol 12 (1) ◽  
pp. 40-79 ◽  
Author(s):  
Daniel J. Sheehan ◽  
Christopher A. Hitchcock ◽  
Carol M. Sibley
Keyword(s):  
Fungal Pathogens ◽  
Antifungal Agents ◽  
Susceptibility Testing ◽  
Fungal Infections ◽  
Mechanisms Of Action ◽  
Current Status ◽  
In Vitro Susceptibility ◽  
Clinical Resistance ◽  
In Vitro Susceptibility Testing

SUMMARY Major developments in research into the azole class of antifungal agents during the 1990s have provided expanded options for the treatment of many opportunistic and endemic fungal infections. Fluconazole and itraconazole have proved to be safer than both amphotericin B and ketoconazole. Despite these advances, serious fungal infections remain difficult to treat, and resistance to the available drugs is emerging. This review describes present and future uses of the currently available azole antifungal agents in the treatment of systemic and superficial fungal infections and provides a brief overview of the current status of in vitro susceptibility testing and the growing problem of clinical resistance to the azoles. Use of the currently available azoles in combination with other antifungal agents with different mechanisms of action is likely to provide enhanced efficacy. Detailed information on some of the second-generation triazoles being developed to provide extended coverage of opportunistic, endemic, and emerging fungal pathogens, as well as those in which resistance to older agents is becoming problematic, is provided.

scholarly journals In Vitro Susceptibility ofCandidaSpecies to Four Antifungal Agents Assessed by the Reference Broth Microdilution Method

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Fahriye Eksi ◽  
Efgan Dogan Gayyurhan ◽  
Iclal Balci
Keyword(s):  
Amphotericin B ◽  
Antifungal Agents ◽  
Antifungal Susceptibility ◽  
Resistance Rate ◽  
Broth Microdilution ◽  
In Vitro Susceptibility ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Dose Dependent

This study was performed to determine the distribution ofCandidaspecies isolated from the blood cultures of the patients hospitalized in our hospital and to investigate their antifungal susceptibility.Candidastrains were identified at species level by using classical methods and API ID 32C (bioMerieux, France) identification kits. The susceptibility of the strains to amphotericin B, fluconazole, voriconazole, and caspofungin was evaluated by using the reference broth microdilution method in document M27-A3 of the Clinical and Laboratory Standards Institute. Of the 111Candidastrains isolated, 47.7% were identified asC. albicansand 52.3% as non-albicansCandidastrains. The MIC ranges were 0.03–1 μg/mL for amphotericin B, 0.125–≥64 μg/mL for fluconazole, 0.03–16 μg/mL for voriconazole, and 0.015–0.25 μg/mL for caspofungin. AllCandidastrains were susceptible to amphotericin B and caspofungin. 10.8% isolates were resistant to fluconazole and 8.1% isolates were dose-dependent susceptible. While 0.9% isolate was resistant to voriconazole, 0.9% isolate was dose-dependent susceptible. In our study,C. albicansandC. parapsilosiswere the most frequently encountered agents of candidemia and it was detected that voriconazole with a low resistance rate might also be used with confidence in the treatment of infections occurring with these agents, primarily besides amphotericin B and caspofungin.

scholarly journals In Vitro Activities of Voriconazole in Combination with Three Other Antifungal Agents against Candida glabrata

2004 ◽  
Vol 48 (9) ◽  
pp. 3317-3322 ◽  
Author(s):  
Francesco Barchiesi ◽  
Elisabetta Spreghini ◽  
Monia Maracci ◽  
Annette W. Fothergill ◽  
Isabella Baldassarri ◽  
...  
Keyword(s):  
Candida Glabrata ◽  
Antifungal Agents ◽  
Beneficial Effects ◽  
Synergistic Interactions ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Disk Diffusion Assay ◽  
Combination Regimens

ABSTRACT Candida glabrata has recently emerged as a significant pathogen involved in both superficial and deep-seated infections. In the present study, a checkerboard broth microdilution method was performed to investigate the in vitro activities of voriconazole (VOR) in combination with terbinafine (TRB), amphotericin B (AMB), and flucytosine (5FC) against 20 clinical isolates of C. glabrata. Synergy, defined as a fractional inhibitory concentration (FIC) index of ≤0.50, was observed in 75% of VOR-TRB, 10% of VOR-AMB, and 5% of VOR-5FC interactions. None of these combinations yielded antagonistic interactions (FIC index > 4). When synergy was not achieved, there was still a decrease in the MIC of one or both drugs used in the combination. In particular, the MICs were reduced to ≤1.0 μg/ml as a result of the combination for all isolates for which the AMB MIC at the baseline was ≥2.0 μg/ml. By a disk diffusion assay, the halo diameters produced by antifungal agents in combination were greater that those produced by each drug alone. Finally, killing curves showed that VOR-AMB exhibited synergistic interactions, while VOR-5FC sustained fungicidal activities against C. glabrata. These studies demonstrate that the in vitro activity of VOR against this important yeast pathogen can be enhanced upon combination with other drugs that have different modes of action or that target a different step in the ergosterol pathway. Further studies are warranted to elucidate the potential beneficial effects of such combination regimens in vivo.

scholarly journals Evaluation of a Modified EUCAST Fragmented-Mycelium Inoculum Method forIn VitroSusceptibility Testing of Dermatophytes and the Activity of Novel Antifungal Agents

2015 ◽  
Vol 59 (6) ◽  
pp. 3675-3682 ◽  
Author(s):  
B. Risslegger ◽  
C. Lass-Flörl ◽  
G. Blum ◽  
M. Lackner
Keyword(s):  
Antifungal Agents ◽  
Susceptibility Testing ◽  
Preparation Method ◽  
Antifungal Susceptibility ◽  
Broth Microdilution ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Inoculum Preparation ◽  
Minimal Effective Concentration

ABSTRACTFor antifungal susceptibility testing of nonsporulating or poorly sporulating dermatophytes, a fragmented-mycelium inoculum preparation method was established and compared to broth microdilution testing according to CLSI and EUCAST guidelines. Moreover, thein vitroactivity of new antifungal agents against dermatophytes was evaluated. Agreement between the mycelial inoculum method and the CLSI broth microdilution method was high (93% to 100%). Echinocandins (minimal effective concentration [MEC], ≤0.5 mg/liter) and posaconazole (MIC, ≤3.00 mg/liter) showed good activity against all tested dermatophytes.

scholarly journals Correlation of In Vitro Activity, Serum Levels, and In Vivo Efficacy of Posaconazole against Rhizopus microsporus in a Murine Disseminated Infection

2009 ◽  
Vol 53 (12) ◽  
pp. 5022-5025 ◽  
Author(s):  
M. Mar Rodríguez ◽  
F. Javier Pastor ◽  
Enrique Calvo ◽  
Valentina Salas ◽  
Deanna A. Sutton ◽  
...  
Keyword(s):  
Serum Levels ◽  
Rhizopus Microsporus ◽  
In Vitro Susceptibility ◽  
In Vivo Efficacy ◽  
Susceptibility Data ◽  
Microdilution Method ◽  
Drug Concentrations ◽  
Broth Microdilution Method

ABSTRACT A broth microdilution method was used to evaluate the in vitro activities of seven antifungal agents against 15 clinical strains of Rhizopus microsporus. Amphotericin B (AMB) and posaconazole (POS) were the most active drugs. In a model of disseminated R. microsporus infection in immunosuppressed mice, we studied the efficacy of POS administered once or twice daily against four of the strains previously tested in vitro and compared it with that of liposomal AMB (LAMB). LAMB was the most effective treatment for the two strains with intermediate susceptibility to POS. For the two POS-susceptible strains, LAMB and POS at 20 mg/kg of body weight twice a day orally showed similar efficacies. The in vivo efficacy of POS administered twice a day orally correlated with the in vitro susceptibility data and the serum drug concentrations.

scholarly journals Comparison of disc diffusion, E-Test and a modified CLSI broth microdilution method for in vitro susceptibility testing of itraconazole, posaconazole and voriconazole against Madurella mycetomatis

2021 ◽  
Author(s):  
Bertrand Nyuykonge ◽  
Lukas van Amelsvoort ◽  
Kimberly Eadie ◽  
Ahmed H. Fahal ◽  
Annelies Verbon ◽  
...  
Keyword(s):  
Low Income ◽  
Susceptibility Testing ◽  
Fungal Infections ◽  
Disc Diffusion ◽  
Broth Microdilution ◽  
In Vitro Susceptibility ◽  
Bead Beating ◽  
Broth Microdilution Method ◽  
Madurella Mycetomatis

For many fungal infections, in vitro susceptibility testing is used to predict if an isolate is resistant or susceptible to the antifungal agent used to treat the fungal infection. For Madurella mycetomatis , the main causative agent of mycetoma, in vitro susceptibility testing currently is not performed on a routine basis. The current in vitro susceptibility testing method is labor intensive and sonication must be done to generate a hyphal inoculum. For endpoint visualization, expensive viability dyes are needed. Here we investigated if the currently used in vitro susceptibility method could be adapted to make it amendable for use in a routine setting which can be used in low income countries, where mycetoma is endemic. First, we developed a methodology in which hyphal fragments can be generated without the need for sonication, by comparing different bead beating methodologies. Next, in vitro susceptibility was assessed using standard broth microdilution assays as well as disc diffusion, E-testing and VIPcheck™ methodologies. We demonstrate that after a hyphal suspension is generated by glass bead beating, disc diffusion, E-testing and VIPcheck™ can be used to determine susceptibility towards itraconazole, posaconazole and voriconazole of Madurella mycetomatis . The MICs found with the E-test were comparable to those obtained with our modified CLSI-based broth microdilution in vitro susceptibility assay for itraconazole and posaconazole. Furthermore, we found an inverse relationship between the zone of inhibition and MIC obtained with E-test and the modified CLSI broth microdilution technique.

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