In vitro activity of four triazole antifungal drugs against clinically common and uncommon yeast species

Background and Purpose: Incidence of fungal infections caused by opportunistic fungal pathogens, such as yeasts and yeast-like species, has undergone an increase in otherwise healthy individuals. These pathogens account for high mortality and show reduced susceptibility to the routine antifungal drugs. Accordingly, antifungal susceptibility testing is an urgent need in the determination of the susceptibility spectrum of antifungals and selection of appropriate antifungal agents for the management of patients with fungal infection.Materials and Methods: The present study was conducted on 110 yeast strains belonging to 15 species recovered from clinical specimens. Susceptibility of the isolates to four antifungal drugs (i.e., fluconazole, itraconazole, voriconazole, and posaconazole) was tested according to the Clinical and Laboratory Standards Institute guidelines M27-A3 and M27-S4.Results: Fluconazole exhibited no activity against 4.3% (n=2) of C. albicans isolates, whereas the remaining 44 isolates had a minimum inhibitory concentration (MIC) range of 0.125-4 μg/ml. Voriconazole had the lowest geometric mean MIC (0.03 μg/ml) against all isolated yeast species, followed by posaconazole (0.07 μg/ml), itraconazole (0.10 μg/ml), and fluconazole (0.60 μg/ml). Overall, all of the isolates had reduced voriconazole MICs with a MIC range of 0.016-0.5 μg/ml, except for one isolate of C. albicans that had a MIC of 1 μg/ml. Candida haemulonii as a multidrug-resistant fungus showed a fluconazole MIC of > 64 μg/ml.Conclusion: The current study provides insight into the antifungal susceptibility profiles of clinically common and uncommon yeast species to four triazole antifungal agents. According to our findings, voriconazole was the most active agent. Awareness about antifungal susceptibility patterns is highly helpful in the selection of appropriate antifungal drugs and identification of the efficiency of the currently used agents.

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In Vitro Antifungal Activity of Luliconazole, Efinaconazole, and Nine Comparators Against Aspergillus and Candida Strains Isolated from Otomycosis

Jundishapur Journal of Microbiology ◽

10.5812/jjm.115902 ◽

2021 ◽

Vol 14 (4) ◽

Author(s):

Gholamreza Shokoohi ◽

Reza Rouhi ◽

Mohammad Etehadnezhad ◽

Bahram Ahmadi ◽

Javad Javidnia ◽

...

Keyword(s):

Antifungal Activity ◽

Candida Species ◽

Fungal Pathogens ◽

Antifungal Agents ◽

Geometric Mean ◽

Antifungal Drugs ◽

High Recurrence Rate ◽

Broth Microdilution ◽

In Vitro Antifungal Activity

Background: Aspergillus and Candida species are the most commonly identified fungal pathogens in otomycosis. However, we usually encounter some difficulties in its treatment because many patients show resistance to antifungal agents and present a high recurrence rate. Objectives: The current research was conducted to compare the in vitro activities of luliconazole (LUL), and efinaconazole (EFN) and the nine comparators on Aspergillus and Candida strains isolated from otomycosis. Methods: The in vitro activities of nine common antifungal drugs (amphotericin B (AMB), voriconazole (VRC), fluconazole (FLU), itraconazole (ITC), ketoconazole (KTO), clotrimazole (CLO), nystatin (NYS), terbinafine (TRB), and caspofungin (CAS)) and two novel new azoles (LUL and EFN) against of 108 clinical isolates of Aspergillus and Candida species obtained from otomycosis were assessed according to the CLSI broth microdilution document. Results: The LUL and EFN had the geometric mean minimum inhibitory concentrations (GM MICs) of 0.098 and 0.109 μg/mL against all Aspergillus strains, respectively. Furthermore, the GM MICs of all Candida isolates for LUL, EFN, CAS, CLO, VRC, AMB, ITC, KTO, FLU, NYS, and TRB were calculated to be 0.133, 0.144, 0.194, 0.219, 0.475, 0.537, 0.655, 1.277, 4.905, 9.372, and 13.592 μg/mL, respectively. Additionally, 6 (35.29%), 2 (11.7%), and 1 (5.88%) Candida isolates were resistant to FLU, CAS, and VRC, respectively. Conclusions: As the findings indicated, LUL and EFN showed the lowest GM MIC values against the examined species. Accordingly, these novel imidazole and triazole antifungal agents can be regarded as proper candidates for the treatment of otomycosis caused by Aspergillus and Candida strains.

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Galleria mellonella for the Evaluation of Antifungal Efficacy against Medically Important Fungi, a Narrative Review

Microorganisms ◽

10.3390/microorganisms8030390 ◽

2020 ◽

Vol 8 (3) ◽

pp. 390 ◽

Cited By ~ 8

Author(s):

Sana Jemel ◽

Jacques Guillot ◽

Kalthoum Kallel ◽

Françoise Botterel ◽

Eric Dannaoui

Keyword(s):

Fungal Pathogens ◽

Galleria Mellonella ◽

Fungal Infections ◽

Antifungal Susceptibility ◽

Antifungal Drugs ◽

New Drugs ◽

Development Of Resistance ◽

Antifungal Efficacy

The treatment of invasive fungal infections remains challenging and the emergence of new fungal pathogens as well as the development of resistance to the main antifungal drugs highlight the need for novel therapeutic strategies. Although in vitro antifungal susceptibility testing has come of age, the proper evaluation of therapeutic efficacy of current or new antifungals is dependent on the use of animal models. Mammalian models, particularly using rodents, are the cornerstone for evaluation of antifungal efficacy, but are limited by increased costs and ethical considerations. To circumvent these limitations, alternative invertebrate models, such as Galleria mellonella, have been developed. Larvae of G. mellonella have been widely used for testing virulence of fungi and more recently have proven useful for evaluation of antifungal efficacy. This model is suitable for infection by different fungal pathogens including yeasts (Candida, Cryptococcus, Trichosporon) and filamentous fungi (Aspergillus, Mucorales). Antifungal efficacy may be easily estimated by fungal burden or mortality rate in infected and treated larvae. The aim of the present review is to summarize the actual data about the use of G. mellonella for testing the in vivo efficacy of licensed antifungal drugs, new drugs, and combination therapies.

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Potential of Nanoparticles in Combating Candida Infections

Letters in Drug Design & Discovery ◽

10.2174/1570180815666181015145224 ◽

2019 ◽

Vol 16 (5) ◽

pp. 478-491 ◽

Cited By ~ 5

Author(s):

Faizan Abul Qais ◽

Mohd Sajjad Ahmad Khan ◽

Iqbal Ahmad ◽

Abdullah Safar Althubiani

Keyword(s):

Targeted Delivery ◽

Recent Progress ◽

Antifungal Agents ◽

Fungal Infections ◽

Fold Increase ◽

Antifungal Drugs ◽

Low Toxicity ◽

Candida Infections ◽

Made In

Aims: The aim of this review is to survey the recent progress made in developing the nanoparticles as antifungal agents especially the nano-based formulations being exploited for the management of Candida infections. Discussion: In the last few decades, there has been many-fold increase in fungal infections including candidiasis due to the increased number of immunocompromised patients worldwide. The efficacy of available antifungal drugs is limited due to its associated toxicity and drug resistance in clinical strains. The recent advancements in nanobiotechnology have opened a new hope for the development of novel formulations with enhanced therapeutic efficacy, improved drug delivery and low toxicity. Conclusion: Metal nanoparticles have shown to possess promising in vitro antifungal activities and could be effectively used for enhanced and targeted delivery of conventionally used drugs. The synergistic interaction between nanoparticles and various antifungal agents have also been reported with enhanced antifungal activity.

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Spectrum and theIn VitroAntifungal Susceptibility Pattern of Yeast Isolates in Ethiopian HIV Patients with Oropharyngeal Candidiasis

International Journal of Microbiology ◽

10.1155/2016/3037817 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8 ◽

Cited By ~ 10

Author(s):

Birhan Moges ◽

Adane Bitew ◽

Aster Shewaamare

Keyword(s):

Antifungal Agents ◽

Antifungal Susceptibility ◽

Antifungal Drugs ◽

Assay Method ◽

Cryptococcus Laurentii ◽

Susceptibility Pattern ◽

Test Procedures ◽

Disk Diffusion Assay ◽

Diffusion Assay

Background.In Ethiopia, little is known regarding the distribution and thein vitroantifungal susceptibility profile of yeasts.Objective.This study was undertaken to determine the spectrum and thein vitroantifungal susceptibility pattern of yeasts isolated from HIV infected patients with OPC.Method.Oral pharyngeal swabs taken from oral lesions of study subjects were inoculated onto Sabouraud Dextrose Agar. Yeasts were identified by employing conventional test procedures and the susceptibility of yeasts to antifungal agents was evaluated by disk diffusion assay method.Result.One hundred and fifty-five yeast isolates were recovered of which 91 isolates were from patients that were not under HAART and 64 were from patients that were under HAART.C. albicanswas the most frequently isolated species followed byC. glabrata, C. tropicalis, C. krusei, C. kefyr, Cryptococcus laurentii, and Rhodotorulaspecies. Irrespective of yeasts isolated and identified, 5.8%, 5.8%, 12.3%, 8.4%, 0.6%, and 1.3% of the isolates were resistant to amphotericin B, clotrimazole, fluconazole, ketoconazole, miconazole, and nystatin, respectively.Conclusion.Yeast colonization rate of 69.2% and 31% resistance to six antifungal agents was documented. These highlight the need for nationwide study on the epidemiology of OPC and resistance to antifungal drugs.

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Acylhydrazones as Antifungal Agents Targeting the Synthesis of Fungal Sphingolipids

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00156-18 ◽

2018 ◽

Vol 62 (5) ◽

Cited By ~ 32

Author(s):

Cristina Lazzarini ◽

Krupanandan Haranahalli ◽

Robert Rieger ◽

Hari Krishna Ananthula ◽

Pankaj B. Desai ◽

...

Keyword(s):

Mammalian Cells ◽

Antifungal Agents ◽

Fungal Infections ◽

Antifungal Drugs ◽

Fungal Resistance ◽

Content Type ◽

Highly Active ◽

Pharmacokinetic Properties ◽

Pass Through

ABSTRACTThe incidence of invasive fungal infections has risen dramatically in recent decades. Current antifungal drugs are either toxic, likely to interact with other drugs, have a narrow spectrum of activity, or induce fungal resistance. Hence, there is a great need for new antifungals, possibly with novel mechanisms of action. Previously our group reported an acylhydrazone called BHBM that targeted the sphingolipid pathway and showed strong antifungal activity against several fungi. In this study, we screened 19 derivatives of BHBM. Three out of 19 derivatives were highly active againstCryptococcus neoformansin vitroand had low toxicity in mammalian cells. In particular, one of them, called D13, had a high selectivity index and showed better activity in an animal model of cryptococcosis, candidiasis, and pulmonary aspergillosis. D13 also displayed suitable pharmacokinetic properties and was able to pass through the blood-brain barrier. These results suggest that acylhydrazones are promising molecules for the research and development of new antifungal agents.

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Identification and in Vitro Susceptibility Pattern of Fungal Pathogens in Immunocompromised Patients with invasive Fungal Infections

10.51429/ejmm30317 ◽

2021 ◽

Vol 30 (3) ◽

pp. 127-134

Author(s):

Shaimaa A.S. Selem ◽

Neveen A. Hassan ◽

Mohamed Z. Abd El-Rahman ◽

Doaa M. Abd El-Kareem

Keyword(s):

Intensive Care ◽

Fungal Infection ◽

Fungal Pathogens ◽

Fungal Infections ◽

Antifungal Susceptibility ◽

Invasive Fungal Infections ◽

Immunocompromised Patients ◽

University Hospitals ◽

Vitek 2

Background: In intensive care units, invasive fungal infections have become more common, particularly among immunocompromised patients. Early identification and starting the treatment of those patients with antifungal therapy is critical for preventing unnecessary use of toxic antifungal agents. Objective: The aim of this research is to determine which common fungi cause invasive fungal infection in immunocompromised patients, as well as their antifungal susceptibility patterns in vitro, in Assiut University Hospitals. Methodology: This was a hospital based descriptive study conducted on 120 patients with clinical suspicion of having fungal infections admitted at different Intensive Care Units (ICUs) at Assiut University Hospitals. Direct microscopic examination and inoculation on Sabouraud Dextrose Agar (SDA) were performed on the collected specimens. Isolated yeasts were classified using phenotypic methods such as chromogenic media (Brilliance Candida agar), germ tube examination, and the Vitek 2 system for certain isolates, while the identification of mould isolates was primarily based on macroscopic and microscopic characteristics. Moulds were tested in vitro for antifungal susceptibility using the disc diffusion, and yeast were tested using Vitek 2 device cards. Results: In this study, 100 out of 120 (83.3%) of the samples were positive for fungal infection. Candida and Aspergillus species were the most commonly isolated fungal pathogens. The isolates had the highest sensitivity to Amphotericin B (95 %), followed by Micafungin (94 %) in an in vitro sensitivity survey. Conclusion: Invasive fungal infections are a leading cause of morbidity and mortality in immunocompromised patients, with Candida albicans being the most frequently isolated yeast from various clinical specimens; however, the rise in resistance, especially to azoles, is a major concern.

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Current and Emerging Azole Antifungal Agents

Clinical Microbiology Reviews ◽

10.1128/cmr.12.1.40 ◽

1999 ◽

Vol 12 (1) ◽

pp. 40-79 ◽

Cited By ~ 676

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.

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Identification of Fungal Pathogens in Otomycosis and Their Drug Sensitivity: Our Experience

International Archives of Otorhinolaryngology ◽

10.1055/s-0038-1626702 ◽

2018 ◽

Vol 22 (04) ◽

pp. 400-403 ◽

Cited By ~ 3

Author(s):

Khaled Ali ◽

Mahmood Hamed ◽

Hameda Hassan ◽

Amira Esmail ◽

Abeer Sheneef

Keyword(s):

Enzymatic Activity ◽

Candida Species ◽

Fungal Pathogens ◽

Antifungal Agents ◽

Susceptibility Testing ◽

Antifungal Susceptibility ◽

Antifungal Susceptibility Testing ◽

Antifungal Drugs ◽

High Recurrence Rate ◽

Fungal Culture

Introduction Otomycosis is a common problem in otolaryngology practice. However, we usually encounter some difficulties in its treatment because many patients show resistance to antifungal agents, and present high recurrence rate. Objectives To determine the fungal pathogens that cause otomycosis as well as their susceptibility to the commonly used antifungal agents. Additionally, to discover the main reasons for antifungal resistance. Methods We conducted an experimental descriptive study on 122 patients clinically diagnosed with otomycosis from April 2016 to April 2017. Aural discharge specimens were collected for direct microscopic examination and fungal culture. In vitro antifungal susceptibility testing was performed against the commonly used antifungal drugs. We tested the isolated fungi for their enzymatic activity. Results Positive fungal infection was found in 102 samples. The most common fungal pathogens were Aspergillus and Candida species, with Aspergillus niger being the predominant isolate (51%). The antifungal susceptibility testing showed that mold isolates had the highest sensitivity to voriconazole (93.48%), while the highest resistance was to fluconazole (100%). For yeast, the highest sensitivity was to nystatin (88.24%), followed by amphotericin B (82.35%), and the highest resistance was to terbinafine (100%), followed by Itraconazole (94.12%). Filamentous fungi expressed a high enzymatic ability, making them more virulent. Conclusion The Aspergillus and Candida species are the most common fungal isolates in otomycosis. Voriconazole and Nystatin are the medications of choice for the treatment of otomycosis in our community. The high virulence of fungal pathogens is owed to their high enzymatic activity. Empirical use of antifungals should be discouraged.

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Antifungal Susceptibility of Dermatophytes Isolated From Cutaneous Fungal Infections: The Vietnamese Experience

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2019.062 ◽

2019 ◽

Vol 7 (2) ◽

pp. 247-249

Author(s):

Chau Van Tro ◽

Khuong Ho Thi Ngoc ◽

Thuong Nguyen Van ◽

Khang Tran Hau ◽

Marco Gandolfi ◽

...

Keyword(s):

Fungal Infections ◽

Antifungal Susceptibility ◽

Antifungal Drugs ◽

Broth Microdilution ◽

Direct Examination ◽

Sensitivity Testing ◽

Microdilution Method ◽

Broth Microdilution Method ◽

Vietnamese Population

AIM: Evaluate the resistance of dermatophytes to systemic antifungal drugs in the Vietnamese population. METHODS: We enrolled 101 patients with cutaneous dermatophytosis at the Dermato-Venereology hospital in HCMC from August 2016 to March 2017. All the specimens were subjected to direct examination (10% KOH mount) and culture on Sabouraud dextrose agar. In vitro antifungal sensitivity testing was done on species isolated from a culture with broth microdilution method. RESULTS: Direct microscopy was positive for dermatophytes in all patients. However this pathogen was found in fungal cultures in only 61.38% of patients. The main causative agent isolated was Trichophyton spp. (90.3%), followed by Microsporum spp. (8%) and Epidermophyton spp. (1.7%). Trichophyton spp. Has shown resistance to fluconazole, griseofulvin, ketoconazole, and itraconazole in 92.9%, 46.4%, 5.4% and 1.8% of strains, respectively. All Microsporum spp. Strains were found resistant to fluconazole and griseofulvin while resistance to ketoconazole was demonstrated in only 20% of strains and none of them was resistant to itraconazole. Epidermophyton spp strains were all resistant to fluconazole, griseofulvin, ketoconazole while none of them was resistant to itraconazole. CONCLUSION: Based upon our results, Itraconazole shows the greatest probability of efficacy in the treatment of cutaneous dermatophytosis in Vietnamese patients.

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In Vitro Activity of Manogepix against Multidrug-Resistant and Panresistant Candida auris from the New York Outbreak

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01124-20 ◽

2020 ◽

Vol 64 (11) ◽

Cited By ~ 1

Author(s):

YanChun Zhu ◽

Shannon Kilburn ◽

Mili Kapoor ◽

Sudha Chaturvedi ◽

Karen Joy Shaw ◽

...

Keyword(s):

New York ◽

Fungal Infections ◽

Geometric Mean ◽

Multidrug Resistant ◽

Antifungal Drugs ◽

New Drugs ◽

Wild Type ◽

Candida Auris ◽

Content Type

ABSTRACT An ongoing Candida auris outbreak in the New York metropolitan area is the largest recorded to date in North America. Laboratory surveillance revealed NY C. auris isolates are resistant to fluconazole, with variable resistance to other currently used broad-spectrum antifungal drugs, and that several isolates are panresistant. Thus, there is an urgent need for new drugs with a novel mechanism of action to combat the resistance challenge. Manogepix (MGX) is a first-in-class agent that targets the fungal Gwt1 enzyme. The prodrug fosmanogepix is currently in phase 2 clinical development for the treatment of fungal infections. We evaluated the susceptibility of 200 New York C. auris isolates to MGX and 10 comparator drugs using CLSI methodology. MGX demonstrated lower MICs than comparators (MIC50 and MIC90, 0.03 mg/liter; range, 0.004 to 0.06 mg/liter). The local epidemiological cutoff value (ECV) for MGX indicated all C. auris isolates were within the population of wild-type (WT) strains; 0.06 mg/liter defines the upper limit of wild type (UL-WT). MGX was 8- to 32-fold more active than the echinocandins, 16- to 64-fold more active than the azoles, and 64-fold more active than amphotericin B. No differences were found in the MGX or comparators’ MIC50, MIC90, or geometric mean (GM) values when subsets of clinical, surveillance, and environmental isolates were evaluated. The range of MGX MIC values for six C. auris panresistant isolates was 0.008 to 0.015 mg/liter, and the median and mode MIC values were 0.015 mg/liter, demonstrating that MGX retains activity against these isolates. These data support further clinical evaluation of fosmanogepix for the treatment of C. auris infections, including highly resistant isolates.

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