scholarly journals Impact of antifungal resistance in Australia

2007 ◽  
Vol 28 (4) ◽  
pp. 174 ◽  
Author(s):  
David Ellis ◽  
Tania Sorrell ◽  
Sharon Chen
Keyword(s):  
Antifungal Activity ◽  
Selection Pressure ◽  
Opportunistic Infections ◽  
Fungal Infections ◽  
Fungal Species ◽  
Antifungal Drugs ◽  
Drug Resistant ◽  
Populations At Risk ◽  
Complete Resistance ◽  
Major Increase

The last two to three decades have seen a major increase in invasive fungal infections (IFIs), a small, but increasing proportion of which are caused by pathogens with partial or complete resistance to antifungal drugs. The increase in IFIs has largely been associated with the increase in immunocompromised and critically ill patients. Opportunistic infections with relatively drug-resistant environmental fungi account for much of the resistance. In addition, amongst the only fungal species to colonise humans, Candida, two species that are resistant (C. krusei) or relatively resistant (C. glabrata) to fluconazole have emerged. In part this is explained by the selection pressure exerted by widespread use of fluconazole. Together with the introduction of new antifungal drugs with selective and/or variable antifungal activity, these changes have stimulated interest in understanding mechanisms and origins of resistance, the identification of resistance in the laboratory and its relationship to clinical outcomes, and in surveillance of clinical isolates and populations at risk of IFIs.

scholarly journals Anticapsular and Antifungal Activity of α-Cyperone

Antibiotics ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 51
Author(s):  
Connor Horn ◽  
Govindsamy Vediyappan
Keyword(s):  
Antifungal Activity ◽  
Fungal Pathogens ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Cyperus Rotundus ◽  
Drug Resistant ◽  
Fungal Virulence ◽  
Medical Needs ◽  
Number Of Patients ◽  
Immunosuppressed Patients

Fungal infections affect 300 million people and cause 1.5 million deaths globally per year. With the number of immunosuppressed patients increasing steadily, there is an increasing number of patients infected with opportunistic fungal infections such as infections caused by the species of Candida and Cryptococcus. In fact, the drug-resistant Can. krusei and the emerging pan-antifungal resistant Can. auris pose a serious threat to human health as the existing limited antifungals are futile. To further complicate therapy, fungi produce capsules and spores that are resistant to most antifungal drugs/host defenses. Novel antifungal drugs are urgently needed to fill unmet medical needs. From screening a collection of medicinal plant sources for antifungal activity, we have identified an active fraction from the rhizome of Cyperus rotundus, the nut grass plant. The fraction contained α-Cyperone, an essential oil that showed fungicidal activity against different species of Candida. Interestingly, the minimal inhibitory concentration of α-Cyperone was reduced 8-fold when combined with a clinical antifungal drug, fluconazole, indicating its antifungal synergistic potential and could be useful for combination therapy. Furthermore, α-Cyperone affected the synthesis of the capsule in Cryp. neoformans, a causative agent of fungal meningitis in humans. Further work on mechanistic understanding of α-Cyperone against fungal virulence could help develop a novel antifungal agent for drug-resistant fungal pathogens.

scholarly journals Drug Repurposing Strategies in the Discovery of Antifungal Agents

2021 ◽  
Author(s):  
Qian Zhang ◽  
Fangyan Liu ◽  
Meng Zeng ◽  
Caiyan Xin ◽  
Jinping Zhang ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Clinical Application ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Immunosuppressive Agents ◽  
Drug Repurposing ◽  
Antifungal Drugs ◽  
Drug Resistant ◽  
Effective Strategies ◽  
Prevention And Treatment

The morbidity and mortality caused by invasive fungal infections is increasing across the globe due to developments in transplant surgery, the use of immunosuppressive agents, and the emergence of drug-resistant fungal strains, which has led to a challenge in terms of treatment due to the limitations of three classes of drugs. Hence, it is imperative to establish effective strategies to identify and design new antifungal drugs. Drug repurposing is an effective way of expanding the application of existing drugs. In the last years, various existing drugs have been shown to be useful in the prevention and treatment of the invasive fungi. In this review, we summarize the currently used antifungal agents. In addition, the most up to date information on the effectiveness of existing drugs with antifungal activity is discussed. Moreover, the antifungal mechanisms of existing drugs are highlighted. These data will provide valuable knowledge to stimulate further investigation and clinical application in this field.

Efficacy of Novel Schiff base Derivatives as Antifungal Compounds in Combination with Approved Drugs Against Candida Albicans

2019 ◽  
Vol 15 (6) ◽  
pp. 648-658 ◽  
Author(s):  
Manzoor Ahmad Malik ◽  
Shabir Ahmad Lone ◽  
Parveez Gull ◽  
Ovas Ahmad Dar ◽  
Mohmmad Younus Wani ◽  
...  
Keyword(s):  
Schiff Base ◽  
Candida Albicans ◽  
Antifungal Activity ◽  
Fungal Infections ◽  
Total Sterol ◽  
Antifungal Drugs ◽  
New Drugs ◽  
Ergosterol Biosynthesis ◽  
Dependent Manner ◽  
Schiff Base Derivatives

Background: The increasing incidence of fungal infections, especially caused by Candida albicans, and their increasing drug resistance has drastically increased in recent years. Therefore, not only new drugs but also alternative treatment strategies are promptly required. Methods: We previously reported on the synergistic interaction of some azole and non-azole compounds with fluconazole for combination antifungal therapy. In this study, we synthesized some non-azole Schiff-base derivatives and evaluated their antifungal activity profile alone and in combination with the most commonly used antifungal drugs- fluconazole (FLC) and amphotericin B (AmB) against four drug susceptible, three FLC resistant and three AmB resistant clinically isolated Candida albicans strains. To further analyze the mechanism of antifungal action of these compounds, we quantified total sterol contents in FLC-susceptible and resistant C. albicans isolates. Results: A pyrimidine ring-containing derivative SB5 showed the most potent antifungal activity against all the tested strains. After combining these compounds with FLC and AmB, 76% combinations were either synergistic or additive while as the rest of the combinations were indifferent. Interestingly, none of the combinations was antagonistic, either with FLC or AmB. Results interpreted from fractional inhibitory concentration index (FICI) and isobolograms revealed 4-10-fold reduction in MIC values for synergistic combinations. These compounds also inhibit ergosterol biosynthesis in a concentration-dependent manner, supported by the results from docking studies. Conclusion: The results of the studies conducted advocate the potential of these compounds as new antifungal drugs. However, further studies are required to understand the other mechanisms and in vivo efficacy and toxicity of these compounds.

Synthesis and Biological Activity of 3-(substitutedphenyl)-6-(4-methoxyphenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine: Part II

2020 ◽  
Vol 18 ◽  
Author(s):  
Niranjan Kaushik ◽  
Nitin Kumar ◽  
Anoop Kumar ◽  
Vikas Sharma
Keyword(s):  
Antifungal Activity ◽  
Opportunistic Infections ◽  
Fungal Infections ◽  
Mass Spectral Data ◽  
Triazole Derivatives ◽  
Mass Spectral ◽  
Fungal Strains ◽  
Antifungal Properties ◽  
Antifungal Potential ◽  
Spectral Data Analysis

Background: Fungal infections are opportunistic infections that become a serious problem to human health. Objective: Considering the antifungal potential of triazole nucleus, the study was carried out with the objective to synthesize some novel triazole derivatives with antifungal potential. Method: 1,2,4-triazole derivatives were synthesized via a two step reaction (reported earlier). The first step involves reaction of substituted benzoic acid with thiocarbohydrazide to form 4-amino-3-(substituted phenyl)-5-mercapto-1, 2, 4-triazole derivatives (1a-1k) while in second step, synthesized compounds (1a-1k) were then subsequently treated with substituted acetophenone to yield substituted (4-methoxyphenyl-7H-[1, 2, 4] triazolo [3, 4-b][1,3,4] thiadiazine derivatives (2a-2k). All synthesized compounds were characterized by IR, 1H NMR, and Mass spectral data analysis and were screened for their antifungal properties against different fungal strains i.e. Candida tropicalis (ATCC-13803, ATCC-20913), Candida albicans (ATCC-60193), Candida inconspicua (ATCC-16783) and Candida glabrata (ATCC-90030, ATCC-2001). Results: Compound 2d displayed better percentage inhibition (26.29%, 24.81%) than fluconazole (24.44%, 22.96%) against ATCC-16783, ATCC-2001 fungal strains respectively at 100µg/ml. Compound 2f also displayed better percentage inhibition (28.51%) against ATCC-90030 as compared to fluconazone (27.4%) at 200 µg/ml. Similarly, compounds 2e and 2j also exhibited better antifungal properties than fluconazole at 200µg/ml. Compound 2e was found most potent against ATCC13803 (30.37%) and ATCC-90030 (30.37%) fungal strains as compared to fluconazole (28.14%, 27.4%) at 200 µg/ml respectively whereas compound 2j exhibited better antifungal activity (28.51%) against ATCC-60193 than fluconazole (27.7%) at 200 µg/ml. Conclusion: The results were in accordance with our assertions for triazole derivatives, as all compounds displayed moderate to good antifungal activity.

scholarly journals Herbal Products and Their Active Constituents Used Alone and in Combination with Antifungal Drugs against Drug-Resistant Candida sp.

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 655
Author(s):  
Anna Herman ◽  
Andrzej Przemysław Herman
Keyword(s):  
Biofilm Formation ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Membrane Transporters ◽  
Drug Resistant ◽  
Herbal Products ◽  
Active Constituents ◽  
Over Expression ◽  
Candida Sp ◽  
Current State

Clinical isolates of Candida yeast are the most common cause of opportunistic fungal infections resistant to certain antifungal drugs. Therefore, it is necessary to detect more effective antifungal agents that would be successful in overcoming such infections. Among them are some herbal products and their active constituents.The purpose of this review is to summarize the current state of knowledge onherbal products and their active constituents havingantifungal activity against drug-resistant Candida sp. used alone and in combination with antifungal drugs.The possible mechanisms of their action on drug-resistant Candida sp. including (1) inhibition of budding yeast transformation into hyphae; (2) inhibition of biofilm formation; (3) inhibition of cell wall or cytoplasmic membrane biosynthesis; (4) ROS production; and (5) over-expression of membrane transporters will be also described.

GROWTH INHIBITORY ACTIVITIES OF THE RHIZOME CRUDE EXTRACT OF Curcuma longa ON THE HUMAN PATHOGENIC FUNGUS Mucor circinelloides

2020 ◽  
Vol 65 (10) ◽  
pp. 82-91
Author(s):  
Phuong Nguyen Anh ◽  
Mai Le Thi Tuyet ◽  
Trung Trieu Anh
Keyword(s):  
Antifungal Activity ◽  
Crude Extract ◽  
Fungal Infections ◽  
Early Stage ◽  
Curcuma Longa ◽  
Pathogenic Fungus ◽  
Mucor Circinelloides ◽  
Antifungal Drugs ◽  
Diffusion Method ◽  
Dilution Method

Mucormycosis is an uncommon but life-threatening invasive fungal infection, mostly occurs in immunocompromised patients. Lacking the appropriate antifungal drugs is one of the reasons that lead to difficulties in the management of mucormycosis. Curcuma longa has been used traditionally and widely to treat various diseases, including fungal infections. In the search for novel antifungal compounds from natural resources, we evaluated the effect of rhizome crude extract of C. longa on Mucor circinelloides – a causal agent of mucormycosis. The results of screening, using broth dilution method and agar-well diffusion method, showed that the C. longa extract exhibited promising antifungal activity against the fungus M. circinelloides. In liquid medium, C. longa extract decreased the ability of spore germination and the speed of hyphae formation of M. circinelloides decreased by up to approximately 70% and 90%, respectively. Besides, in a solid medium, the crude extract presented similar activity with amphotericin B (400 μg\mL) in decreasing the growth of M. circinelloides by nearly 77%. Moreover, the extract of C. longa also likely to induce the yeast-like type of growth of the dimorphic M. circinelloides in the early stage. These results suggest the plant could be a potential source for further study on biochemical components and the mechanism of its antifungal activity.

Practical Approach to the Pathologic Diagnosis of Mixed Filamentous Fungal Infections in Burn Wounds: A Case Series

2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S133-S133
Author(s):  
A D Pyden ◽  
I Solomon ◽  
A Laga Canales
Keyword(s):  
Opportunistic Infections ◽  
Fungal Infections ◽  
Case Series ◽  
Fungal Species ◽  
Molecular Testing ◽  
Burn Wounds ◽  
Tissue Sections ◽  
True Infection ◽  
Extensive Burn

Abstract Introduction/Objective Opportunistic infections by fungi are a major source of morbidity and mortality in patients suffering from extensive burn wounds. Here we review a series of cases of infections by multiple fungi in burn wounds as diagnosed by histopathology and outline the key features for the pathologist to include in the report. Methods/Case Report Biopsies from patients with more than one fungal species identified in the laboratory in a concurrent culture or by PCR were included in this study. Three cases are presented with multiple fungi identified. Each case had yeast and at least one different hyaline mold species present on pathology; two cases additionally had mucormycetes present, with angioinvasion in one case. All organisms requiried microbiologic cultures and variably required molecular testing for full identification. Results (if a Case Study enter NA) N/A Conclusion Pathologists should be aware of the possibility of infection by multiple fungal species in burn wounds. Fungal morphology in tissue sections should allow for detection and distinction of mucormyctes and other hyaline molds. Histopathologic correlation with culture and/or PCR results is essential to distinguish potential contaminants from true infection.

scholarly journals Synergistic Antifungal Activity of Chitosan with Fluconazole against Candida albicans, Candida tropicalis, and Fluconazole-Resistant Strains

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5114
Author(s):  
Wei-Hsuan Lo ◽  
Fu-Sheng Deng ◽  
Chih-Jung Chang ◽  
Ching-Hsuan Lin
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Candida Tropicalis ◽  
Inhibitory Effect ◽  
Antifungal Drugs ◽  
Drug Resistant ◽  
Combinational Treatment ◽  
Fluconazole Resistant ◽  
Resistant Strains ◽  
Drug Resistant Strains

(1) Background: Few antifungal drugs are currently available, and drug-resistant strains have rapidly emerged. Thus, the aim of this study is to evaluate the effectiveness of the antifungal activity from a combinational treatment of chitosan with a clinical antifungal drug on Candida albicans and Candida tropicalis. (2) Methods: Minimum inhibitory concentration (MIC) tests, checkerboard assays, and disc assays were employed to determine the inhibitory effect of chitosan with or without other antifungal drugs on C. albicans and C. tropicalis. (3) Results: Treatment with chitosan in combination with fluconazole showed a great synergistic fungicidal effect against C. albicans and C. tropicalis, but an indifferent effect on antifungal activity when challenged with chitosan-amphotericin B or chitosan-caspofungin simultaneously. Furthermore, the combination of chitosan and fluconazole was effective against drug-resistant strains. (4) Conclusions: These findings provide strong evidence that chitosan in combination with fluconazole is a promising therapy against two Candida species and its drug-resistant strains.

scholarly journals Amphotericin B-conjugated polypeptide hydrogels as a novel innovative strategy for fungal infections

2018 ◽  
Vol 5 (3) ◽  
pp. 171814 ◽  
Author(s):  
Chang Shu ◽  
Tengfei Li ◽  
Wen Yang ◽  
Duo Li ◽  
Shunli Ji ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Antifungal Activity ◽  
Amphotericin B ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Water Soluble ◽  
Naphthalene Acetic Acid ◽  
Innovative Strategy ◽  
Molecular Arrangement

The present work is focused on the design and development of novel amphotericin B (AmB)-conjugated biocompatible and biodegradable polypeptide hydrogels to improve the antifungal activity. Using three kinds of promoting self-assembly groups (2-naphthalene acetic acid (Nap), naproxen (Npx) and dexamethasone (Dex)) and polypeptide sequence (Phe-Phe-Asp-Lys-Tyr, FFDKY), we successfully synthesized the Nap-FFDK(AmB)Y gels, Npx-FFDK(AmB)Y gels and Dex-FFDK(AmB)Y gels. The AmB-conjugated hydrogelators are highly soluble in different aqueous solutions. The cryo-transmission electron microscopy and scanning electron microscopy micrographs of hydrogels afford nanofibres with a width of 20–50 nm. Powder X-ray diffraction analyses demonstrate that the crystalline structures of the AmB and Dex are changed into amorphous structures after the formation of hydrogels. Circular dichroism spectra of the solution of blank carriers and the corresponding drug deliveries further help elucidate the molecular arrangement in gel phase, indicating the existence of turn features. The in vitro drug releases suggest that the AmB-conjugated hydrogels are suitable as drug-controlled release vehicles for hydrophobic drugs. The antifungal effect of AmB-conjugated hydrogels significantly exhibits the antifungal activity against Candida albicans . The results of the present study indicated that the AmB-conjugated hydrogels are suitable carriers for poorly water soluble drugs and for enhancement of therapeutic efficacy of antifungal drugs.

scholarly journals Prevalence and Fluconazole Susceptibility Profile of Candida spp. Clinical Isolates in a Brazilian Tertiary Hospital in Minas Gerais, Brazil

2015 ◽  
Vol 87 (2 suppl) ◽  
pp. 1349-1359 ◽  
Author(s):  
Athayde Neves-Junior ◽  
Ana Carolina Cartágenes-Pinto ◽  
Débora A.S. Rocha ◽  
Leandro F. Reis de Sá ◽  
Maria de Lourdes Junqueira ◽  
...  
Keyword(s):  
Opportunistic Infections ◽  
Fungal Infections ◽  
Tertiary Hospital ◽  
Antifungal Drugs ◽  
Control Measures ◽  
Clinical Isolates ◽  
University Hospital ◽  
Effective Control ◽  
Candida Spp ◽  
Resistance Phenotype

Candidiasis has become an important concern for clinical practice, especially with the increasing incidence of immunocompromised patients. In this scenario, the development resistance to fluconazole presents a challenge for treating these opportunistic infections. The aim of this study was to evaluate some epidemiology features of Candidainfections in a Brazilian University Hospital using data, previously unavailable. We observed that 44% of the 93 clinical isolates tested, belonged to Candida albicansspecies and 56% belonged to non-Candida albicansspecies (mainly Candida tropicalis and Candida glabrata). Most strains were isolated from urine samples where C. albicans was predominantly detected. 29 strains presented a fluconazole resistance phenotype and of these, 22 were chemosensitised by FK506, a classical inhibitor of ABC transporters related to azoles resistance. These data suggest the probable role of efflux pumps in this resistance phenotype. Our study highlights the need for developing effective control measures for fungal infections, rational use of antifungal drugs and development of new molecules able to abrogate the active transport of antifungals.

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