Journal articles: 'Antifungal drugs'

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Cross, J. T., S. L. Hickerson, and T. Yamauchi. "Antifungal Drugs." Pediatrics in Review 16, no. 4 (April 1, 1995): 123–29. http://dx.doi.org/10.1542/pir.16-4-123.

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Cross, J. Thomas, Steven L. Hickerson, and Terry Yamauchi. "Antifungal Drugs." Pediatrics In Review 16, no. 4 (April 1, 1995): 123–29. http://dx.doi.org/10.1542/pir.16.4.123.

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Introduction Fungi have been recognized as pathogens for many years. However, the incidence of fungal infections in the pediatric population has increased substantially due to the increased use of broad-spectrum antibiotics, immunosuppressive agents, hyperalimentation products, and central venous catheters in addition to the acquired immunodeficiency syndrome (AIDS) epidemic. The physician involved with the care of children should know the agents effective against these pathogens (Table 1). Amphotericin B has a long history of both efficacy and toxicity because it was the only available systemic agent for many years. With the introduction of ketoconazole, fluconazole, and itraconazole over the past decade, the decision of which agent to use has become much more difficult. Clinical trials are underway to help answer these questions, but until these are completed, the clinician must weigh the risks and benefits of therapy for each patient individually. Amphotericin B BACKGROUND Amphotericin B is entering its fourth decade as an antifungal agent. Since its introduction in the mid-1950s, it has been the cornerstone of management of systemic fungal infections. Even with the introduction of the azoles, it continues to be the treatment of choice for many conditions. CHEMISTRY, MECHANISM OF ACTION Streptomyces nodosus, a soil actinomycete, is the source of the amphotericins A and B. Amphotericin B is the commercially available product, and it may contain a small amount (<5%) of amphotericin A.

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Houšť, Jiří, Jaroslav Spížek, and Vladimír Havlíček. "Antifungal Drugs." Metabolites 10, no. 3 (March 12, 2020): 106. http://dx.doi.org/10.3390/metabo10030106.

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We reviewed the licensed antifungal drugs and summarized their mechanisms of action, pharmacological profiles, and susceptibility to specific fungi. Approved antimycotics inhibit 1,3-β-d-glucan synthase, lanosterol 14-α-demethylase, protein, and deoxyribonucleic acid biosynthesis, or sequestrate ergosterol. Their most severe side effects are hepatotoxicity, nephrotoxicity, and myelotoxicity. Whereas triazoles exhibit the most significant drug–drug interactions, echinocandins exhibit almost none. The antifungal resistance may be developed across most pathogens and includes drug target overexpression, efflux pump activation, and amino acid substitution. The experimental antifungal drugs in clinical trials are also reviewed. Siderophores in the Trojan horse approach or the application of siderophore biosynthesis enzyme inhibitors represent the most promising emerging antifungal therapies.

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Warnock, D. W. "Antifungal drugs." Current Opinion in Infectious Diseases 1, no. 3 (May 1988): 375–79. http://dx.doi.org/10.1097/00001432-198805000-00006.

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Warnock, D. W. "Antifungal drugs." Current Opinion in Infectious Diseases 2, no. 3 (June 1989): 362–66. http://dx.doi.org/10.1097/00001432-198906000-00005.

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Warnock, David W. "Antifungal drugs." Current Opinion in Infectious Diseases 3, no. 6 (December 1990): 765–69. http://dx.doi.org/10.1097/00001432-199012000-00005.

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Akkuş, İlknur, and Birgül Kaçmaz. "Antifungal drugs." Journal of Current Hematology & Oncology Research 1, no. 2 (May 29, 2023): 41–46. http://dx.doi.org/10.51271/jchor-0010.

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Fungal infections continue to emerge as an important cause of infectious disease and mortality in humans. Amphotericin B deoxycholate (ABD), was the first antifungal that was discovered, and it was released in 1958, and flucytosine, which was developed later and is effective against Candida and Cryptococcus, was introduced in 1978. The discovery of first-generation azoles (fluconazole and itraconazole) in the 1990s has created a new step in the treatment of fungi. In the years that followed, with the development of lipid formulations of amphotericin B, the introduction of second-generation azoles, and the release of the most recently developed class, echinocandins, the foundations of today’s existing antifungal classes were laid. This article is aimed to review the mechanism of action, side effects and clinical use indications of the main antifungal drugs used in the treatment of systemic fungal infections.

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Perfect, John R. "Molecular targets for new antifungal drugs." Canadian Journal of Botany 73, S1 (December 31, 1995): 1187–91. http://dx.doi.org/10.1139/b95-377.

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Fungal infections in man and animals have a significant impact on health. However, there are only a few antifungal agents available for treatment of invasive mycoses. Further understanding of fungal molecular pathogenesis in collaboration with biochemistry and molecular modeling strategies should be able to develop new selective fungicidal agents. An example of this approach is Cryptococcus neoformans, which is reviewed in this discussion, as a model system for identification of antifungal molecular targets. Key words: antifungals, fungi, treatment, cryptococcosis, molecular biology, targets.

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Van Daele, Ruth, Isabel Spriet, Joost Wauters, Johan Maertens, Toine Mercier, Sam Van Hecke, and Roger Brüggemann. "Antifungal drugs: What brings the future?" Medical Mycology 57, Supplement_3 (June 1, 2019): S328—S343. http://dx.doi.org/10.1093/mmy/myz012.

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AbstractThe high burden and growing prevalence of invasive fungal infections (IFIs), the toxicity and interactions associated with current antifungal drugs, as well as the increasing resistance, ask for the development of new antifungal drugs, preferably with a novel mode of action. Also, the availability of oral or once-weekly alternatives would enable ambulatory treatment resulting in an improved patient's comfort and therapy adherence. However, only one new azole and two new posaconazole-formulations were marketed over the last decade. This review focuses on the antifungal drugs in the pipeline undergoing clinical evaluation. First, the newest azole, isavuconazole, with its improved safety profile and reduction in DDIs, will be discussed. Moreover, there are two glucan synthase inhibitors (GSIs) in the antifungal pipeline: rezafungin (CD101), a long-acting echinocandin with an improved stability that enables once weekly administration, and SCY-078, an orally available GSI with efficacy against azole- and echinocandin resistant isolates. A new oral formulation of amphotericin B will also be presented. Moreover, the first representative of a new antifungal class, the orotomides, with a broad spectrum and no cross-resistance with current antifungal classes, will be discussed. Finally, an overview of other antifungals that are still in earlier clinical development phases, is provided.

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DiDomenico, Beth. "Novel antifungal drugs." Current Opinion in Microbiology 2, no. 5 (October 1999): 509–15. http://dx.doi.org/10.1016/s1369-5274(99)00009-0.

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Denning, David W. "Echinocandin antifungal drugs." Lancet 362, no. 9390 (October 2003): 1142–51. http://dx.doi.org/10.1016/s0140-6736(03)14472-8.

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Siles, Samuel A., Anand Srinivasan, Christopher G. Pierce, José L. Lopez-Ribot, and Anand K. Ramasubramanian. "High-Throughput Screening of a Collection of Known Pharmacologically Active Small Compounds for Identification of Candida albicans Biofilm Inhibitors." Antimicrobial Agents and Chemotherapy 57, no. 8 (May 20, 2013): 3681–87. http://dx.doi.org/10.1128/aac.00680-13.

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ABSTRACTCandida albicansis the most common etiologic agent of systemic fungal infections with unacceptably high mortality rates. The existing arsenal of antifungal drugs is very limited and is particularly ineffective againstC. albicansbiofilms. To address the unmet need for novel antifungals, particularly those active against biofilms, we have screened a small molecule library consisting of 1,200 off-patent drugs already approved by the Food and Drug Administration (FDA), the Prestwick Chemical Library, to identify inhibitors ofC. albicansbiofilm formation. According to their pharmacological applications that are currently known, we classified these bioactive compounds as antifungal drugs, as antimicrobials/antiseptics, or as miscellaneous drugs, which we considered to be drugs with no previously characterized antifungal activity. Using a 96-well microtiter plate-based high-content screening assay, we identified 38 pharmacologically active agents that inhibitC. albicansbiofilm formation. These drugs were subsequently tested for their potency and efficacy against preformed biofilms, and we identified three drugs with novel antifungal activity. Thus, repurposing FDA-approved drugs opens up a valuable new avenue for identification and potentially rapid development of antifungal agents, which are urgently needed.

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Kim, Jong H., Luisa W. Cheng, Kathleen L. Chan, Christina C. Tam, Noreen Mahoney, Mendel Friedman, Mikhail Martchenko Shilman, and Kirkwood M. Land. "Antifungal Drug Repurposing." Antibiotics 9, no. 11 (November 15, 2020): 812. http://dx.doi.org/10.3390/antibiotics9110812.

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Control of fungal pathogens is increasingly problematic due to the limited number of effective drugs available for antifungal therapy. Conventional antifungal drugs could also trigger human cytotoxicity associated with the kidneys and liver, including the generation of reactive oxygen species. Moreover, increased incidences of fungal resistance to the classes of azoles, such as fluconazole, itraconazole, voriconazole, or posaconazole, or echinocandins, including caspofungin, anidulafungin, or micafungin, have been documented. Of note, certain azole fungicides such as propiconazole or tebuconazole that are applied to agricultural fields have the same mechanism of antifungal action as clinical azole drugs. Such long-term application of azole fungicides to crop fields provides environmental selection pressure for the emergence of pan-azole-resistant fungal strains such as Aspergillus fumigatus having TR34/L98H mutations, specifically, a 34 bp insertion into the cytochrome P450 51A (CYP51A) gene promoter region and a leucine-to-histidine substitution at codon 98 of CYP51A. Altogether, the emerging resistance of pathogens to currently available antifungal drugs and insufficiency in the discovery of new therapeutics engender the urgent need for the development of new antifungals and/or alternative therapies for effective control of fungal pathogens. We discuss the current needs for the discovery of new clinical antifungal drugs and the recent drug repurposing endeavors as alternative methods for fungal pathogen control.

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Rayan, Mahmoud, Ziyad Abdallah, Saleh Abu-Lafi, Mahmud Masalha, and Anwar Rayan. "Indexing Natural Products for their Antifungal Activity by Filters-based Approach: Disclosure of Discriminative Properties." Current Computer-Aided Drug Design 15, no. 3 (April 10, 2019): 235–42. http://dx.doi.org/10.2174/1573409914666181017100532.

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<P>Background: A considerable worldwide increase in the rate of invasive fungal infections and resistance toward antifungal drugs was witnessed during the past few decades. Therefore, the need for newer antifungal candidates is paramount. Nature has been the core source of therapeutics for thousands of years, and an impressive number of modern drugs including antifungals were derived from natural sources. In order to facilitate the recognition of potential candidates that can be derived from natural sources, an iterative stochastic elimination optimization technique to index natural products for their antifungal activity was utilized. Methods: A set of 240 FDA-approved antifungal drugs, which represent the active domain, and a set of 2,892 natural products, which represent the inactive domain, were used to construct predictive models and to index natural products for their antifungal bioactivity. The area under the curve for the produced predictive model was 0.89. When applying it to a database that is composed of active/inactive chemicals, we succeeded to detect 42% of the actives (antifungal drugs) in the top one percent of the screened chemicals, compared with one-percent when using a random model. Results and Conclusion: Eight natural products, which were highly scored as likely antifungal drugs, are disclosed. Searching PubMed showed only one molecule (Flindersine) out of the eight that have been tested was reported as an antifungal. The other seven phytochemicals await evaluation for their antifungal bioactivity in a wet laboratory.</P>

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Carmo, Anália, Marilia Rocha, Patricia Pereirinha, Rui Tomé, and Eulália Costa. "Antifungals: From Pharmacokinetics to Clinical Practice." Antibiotics 12, no. 5 (May 9, 2023): 884. http://dx.doi.org/10.3390/antibiotics12050884.

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The use of antifungal drugs started in the 1950s with polyenes nystatin, natamycin and amphotericin B-deoxycholate (AmB). Until the present day, AmB has been considered to be a hallmark in the treatment of invasive systemic fungal infections. Nevertheless, the success and the use of AmB were associated with severe adverse effects which stimulated the development of new antifungal drugs such as azoles, pyrimidine antimetabolite, mitotic inhibitors, allylamines and echinochandins. However, all of these drugs presented one or more limitations associated with adverse reactions, administration route and more recently the development of resistance. To worsen this scenario, there has been an increase in fungal infections, especially in invasive systemic fungal infections that are particularly difficult to diagnose and treat. In 2022, the World Health Organization (WHO) published the first fungal priority pathogens list, alerting people to the increased incidence of invasive systemic fungal infections and to the associated risk of mortality/morbidity. The report also emphasized the need to rationally use existing drugs and develop new drugs. In this review, we performed an overview of the history of antifungals and their classification, mechanism of action, pharmacokinetic/pharmacodynamic (PK/PD) characteristics and clinical applications. In parallel, we also addressed the contribution of fungi biology and genetics to the development of resistance to antifungal drugs. Considering that drug effectiveness also depends on the mammalian host, we provide an overview on the roles of therapeutic drug monitoring and pharmacogenomics as means to improve the outcome, prevent/reduce antifungal toxicity and prevent the emergence of antifungal resistance. Finally, we present the new antifungals and their main characteristics.

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Ganesan, Priya, Dhanraj Ganapathy, Saravanan Sekaran, Karthikeyan Murthykumar, Ashok K. Sundramoorthy, Sivaperumal Pitchiah, and Rajeshkumar Shanmugam. "Molecular Mechanisms of Antifungal Resistance in Mucormycosis." BioMed Research International 2022 (October 13, 2022): 1–8. http://dx.doi.org/10.1155/2022/6722245.

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Mucormycosis is one among the life-threatening fungal infections with high morbidity and mortality. It is an uncommon and rare infection targeting people with altered immunity. This lethal infection induced by fungi belonging to the Mucorales family is very progressive in nature. The incidence has increased in recent decades owing to the rise in immunocompromised patients. Disease management involves a multimodal strategy including early administration of drugs and surgical removal of infected tissues. Among the antifungals, azoles and amphotericin B remain the gold standard drugs of choice for initial treatment. The order Mucorales are developing a high level of resistance to the available systemic antifungal drugs, and the efficacy still remains below par. Deciphering the molecular mechanisms behind the antifungal resistance in Mucormycosis would add vital information to our available antifungal armamentarium and design novel therapies. Therefore, in this review, we have discussed the mechanisms behind Mucormycosis antifungal resistance. Moreover, this review also highlights the basic mechanisms of action of antifungal drugs and the resistance landscape which is expected to augment future treatment strategies.

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Smitherman, L. "In Brief: Antifungal Drugs." Pediatrics in Review 37, no. 6 (June 1, 2016): 267–68. http://dx.doi.org/10.1542/pir.2015-0171.

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Ben-Ami, Ronen, and Dimitrios P. Kontoyiannis. "Resistance to Antifungal Drugs." Infectious Disease Clinics of North America 35, no. 2 (June 2021): 279–311. http://dx.doi.org/10.1016/j.idc.2021.03.003.

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Hay, Rj. "Antifungal drugs-an introduction." Journal of Dermatological Treatment 1, sup2 (January 1990): 1–3. http://dx.doi.org/10.3109/09546639009089020.

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Dismukes, W. E. "Introduction to Antifungal Drugs." Clinical Infectious Diseases 30, no. 4 (April 1, 2000): 653–57. http://dx.doi.org/10.1086/313748.

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HAY, R. J. "The azole antifungal drugs." Journal of Antimicrobial Chemotherapy 20, no. 1 (1987): 1–3. http://dx.doi.org/10.1093/jac/20.1.1.

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Vanreppelen, Giel, Jurgen Wuyts, Patrick Van Dijck, and Paul Vandecruys. "Sources of Antifungal Drugs." Journal of Fungi 9, no. 2 (January 28, 2023): 171. http://dx.doi.org/10.3390/jof9020171.

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Due to their eukaryotic heritage, the differences between a fungal pathogen’s molecular makeup and its human host are small. Therefore, the discovery and subsequent development of novel antifungal drugs are extremely challenging. Nevertheless, since the 1940s, researchers have successfully uncovered potent candidates from natural or synthetic sources. Analogs and novel formulations of these drugs enhanced the pharmacological parameters and improved overall drug efficiency. These compounds ultimately became the founding members of novel drug classes and were successfully applied in clinical settings, offering valuable and efficient treatment of mycosis for decades. Currently, only five different antifungal drug classes exist, all characterized by a unique mode of action; these are polyenes, pyrimidine analogs, azoles, allylamines, and echinocandins. The latter, being the latest addition to the antifungal armamentarium, was introduced over two decades ago. As a result of this limited arsenal, antifungal resistance development has exponentially increased and, with it, a growing healthcare crisis. In this review, we discuss the original sources of antifungal compounds, either natural or synthetic. Additionally, we summarize the existing drug classes, potential novel candidates in the clinical pipeline, and emerging non-traditional treatment options.

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Sabtharishi*, Vanathi, Radhika Katragadda, and Thyagarajan Ravinder. "A study on the antifungal susceptibility pattern of dermatophytes isolated in a tertiary care hospital." International Journal of Bioassays 6, no. 05 (May 6, 2017): 5379. http://dx.doi.org/10.21746/ijbio.2017.05.003.

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Recent years, due to increased usage of antifungal treatment worldwide, there is an increased chance of rising resistance among antifungal drugs too. Dermatophytic infections causes’ superficial mycosis and it affects skin, hair and nail. These infections are more common and antifungal drugs are used everywhere to treat those common infections. To conduct a study by determining the antifungal susceptibility pattern in dermatophytic isolates from patients attending dermatology OPD in a tertiary care hospital. A total of 217 samples like hair, nail and skin scrapings were obtained and isolation of dermatophytes was done. Antifungal susceptibility testing for dermatophytes was performed by micro broth dilution method. Antifungal drugs tested were Griseofulvin, Fluconazole, Itraconazole and Ketoconazole. Minimum inhibitory concentration for each drug for fungal isolates was tested and results studied. Fluconazole showed a higher MIC values in the range of 1-8µg/ml. Itraconazole showed the lowest MIC values by micro broth dilution method. Since there is limitation of standard guidelines and protocol, meticulous research must be conducted on effect of antifungals and derive at universally implementable guidelines.

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Cordisco, Estefanía, Maximiliano Sortino, and Laura Svetaz. "Antifungal Activity of Traditional Medicinal Plants from Argentina: Effect of their Combination with Antifungal Drugs." Current Traditional Medicine 5, no. 1 (June 3, 2019): 75–95. http://dx.doi.org/10.2174/2215083804666181002111456.

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Background and Objective: The incidence of fungal infections has experienced a marked increase in the last two decades being limited to a few drugs with serious drawbacks. Combination therapy has emerged as an approach to improve the efficacy of currently used antifungal therapy that also may delay the evolution of resistance. Method: The objectives of this work are to present a bibliographic search on the plants used in traditional medicine in Argentina for ailments related to fungal infections and to investigate the antifungal activity of currently used antifungal drugs in combination with natural extracts. Results: Results of the bibliographic investigation showed that 153 species belonging to 56 families and 120 genera from Argentina are applied to treat signs and symptoms considered to maintain ethnopharmacological uses related to fungal infections, mainly for skin and mucosal conditions. Conclusion: Regarding the evaluation of the antifungal activity of combinations between extracts and antifungal drugs, we observed that extracts from plants species belonging to a genera traditionally used for ailments related to fungal infections have more chances of enhancing the activity of amphotericin B, fluconazole and itraconazole. In addition, we observed that there is a greater chance of finding an enhancement in the activity of the commercial antifungals when the combination is performed with extracts that have shown activity in solitary. Nevertheless, inactive extracts that would have been discarded according to the classic strategy displayed activity in combination and they continue being potential candidates in the search for new antifungals.

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Jemel, Sana, Jacques Guillot, Kalthoum Kallel, Françoise Botterel, and Eric Dannaoui. "Galleria mellonella for the Evaluation of Antifungal Efficacy against Medically Important Fungi, a Narrative Review." Microorganisms 8, no. 3 (March 11, 2020): 390. http://dx.doi.org/10.3390/microorganisms8030390.

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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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Cai, Tian, Youming Liao, Zhenhua Chen, Yingchang Zhu, and Xincai Qiu. "The Influence of Different Triazole Antifungal Agents on the Pharmacokinetics of Cyclophosphamide." Annals of Pharmacotherapy 54, no. 7 (January 1, 2020): 676–83. http://dx.doi.org/10.1177/1060028019896894.

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Background: Cyclophosphamide is one of the most important chemotherapeutic drugs. Known as a widely accepted treatment strategy, chemotherapy may damage the immune function of cancer patients; as a result, invasive fungal infections (IFIs) occur. Triazole antifungal agents are the most acceptable drugs for IFI treatment, especially those infections caused by chemotherapy. Objective: We aimed to investigate the effects of different triazole antifungal drugs, including fluconazole, itraconazole, and ketoconazole, on the pharmacokinetics (PK) of cyclophosphamide. In addition, we also characterize the potential drug-drug interactions (DDIs) between cyclophosphamide and various triazole antifungal drugs. Methods: The necessary pharmacokinetic parameters and physicochemical data were obtained from published studies. Physiologically based pharmacokinetic (PBPK) models were developed and validated in virtual subjects using Simcyp software. The validated PBPK models were used to evaluate potential DDIs between cyclophosphamide and different triazole antifungal agents in cancer patients. Triazole antifungal agents were simulated by oral administration, whereas cyclophosphamide was simulated by intravenous administration. Results: Simulated plasma concentration-time curves of fluconazole, itraconazole, ketoconazole, and cyclophosphamide were in good consistency with the observed profiles. Our results suggested that the pharmacokinetic parameters of cyclophosphamide were increased by various extents when coadministered with different triazole antifungals. The area under the plasma concentration-time curve of cyclophosphamide was increased when combined with fluconazole, itraconazole, or ketoconazole. Conclusions and Relevance: Ketoconazole had the greatest effect on the PK of cyclophosphamide among the 3 triazole antifungals. Our study provides clues that the toxicity and adverse drug reactions that are associated with cyclophosphamide should be closely monitored when coadministered with ketoconazole.

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Soe, Hay Man Saung Hnin, Phyo Darli Maw, Thorsteinn Loftsson, and Phatsawee Jansook. "A Current Overview of Cyclodextrin-Based Nanocarriers for Enhanced Antifungal Delivery." Pharmaceuticals 15, no. 12 (November 22, 2022): 1447. http://dx.doi.org/10.3390/ph15121447.

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Fungal infections are an extremely serious health problem, particularly in patients with compromised immune systems. Most antifungal agents have low aqueous solubility, which may hamper their bioavailability. Their complexation with cyclodextrins (CDs) could increase the solubility of antifungals, facilitating their antifungal efficacy. Nanoparticulate systems are promising carriers for antifungal delivery due to their ability to overcome the drawbacks of conventional dosage forms. CD-based nanocarriers could form beneficial combinations of CDs and nanoparticulate platforms. These systems have synergistic or additive effects regarding improved drug loading, enhanced chemical stability, and enhanced drug permeation through membranes, thereby increasing the bioavailability of drugs. Here, an application of CD in antifungal drug formulations is reviewed. CD-based nanocarriers, such as nanoparticles, liposomes, nanoemulsions, nanofibers, and in situ gels, enhancing antifungal activity in a controlled-release manner and possessing good toxicological profiles, are described. Additionally, the examples of current, updated CD-based nanocarriers loaded with antifungal drugs for delivery by various routes of administration are discussed and summarized.

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Freitas e Silva, Kleber S., Lívia C. Silva, Relber A. Gonçales, Bruno J. Neves, Célia M. A. Soares, and Maristela Pereira. "Setting New Routes for Antifungal Drug Discovery Against Pathogenic Fungi." Current Pharmaceutical Design 26, no. 14 (May 15, 2020): 1509–20. http://dx.doi.org/10.2174/1381612826666200317125956.

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: Fungal diseases are life-threatening to human health and responsible for millions of deaths around the world. Fungal pathogens lead to a high number of morbidity and mortality. Current antifungal treatment comprises drugs, such as azoles, echinocandins, and polyenes and the cure is not guaranteed. In addition, such drugs are related to severe side effects and the treatment lasts for an extended period. Thus, setting new routes for the discovery of effective and safe antifungal drugs should be a priority within the health care system. The discovery of alternative and efficient antifungal drugs showing fewer side effects is time-consuming and remains a challenge. Natural products can be a source of antifungals and used in combinatorial therapy. The most important natural products are antifungal peptides, antifungal lectins, antifungal plants, and fungi secondary metabolites. Several proteins, enzymes, and metabolic pathways could be targets for the discovery of efficient inhibitor compounds and recently, heat shock proteins, calcineurin, salinomycin, the trehalose biosynthetic pathway, and the glyoxylate cycle have been investigated in several fungal species. HSP protein inhibitors and echinocandins have been shown to have a fungicidal effect against azole-resistant fungi strains. Transcriptomic and proteomic approaches have advanced antifungal drug discovery and pointed to new important specific-pathogen targets. Certain enzymes, such as those from the glyoxylate cycle, have been a target of antifungal compounds in several fungi species. Natural and synthetic compounds inhibited the activity of such enzymes and reduced the ability of fungal cells to transit from mycelium to yeast, proving to be promisor antifungal agents. Finally, computational biology has developed effective approaches, setting new routes for early antifungal drug discovery since normal approaches take several years from discovery to clinical use. Thus, the development of new antifungal strategies might reduce the therapeutic time and increase the quality of life of patients.

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Monk, Brian C., and Mikhail V. Keniya. "Roles for Structural Biology in the Discovery of Drugs and Agrochemicals Targeting Sterol 14α-Demethylases." Journal of Fungi 7, no. 2 (January 20, 2021): 67. http://dx.doi.org/10.3390/jof7020067.

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Antifungal drugs and antifungal agrochemicals have significant limitations. These include several unintended consequences of their use including the growing importance of intrinsic and acquired resistance. These problems underpin an increasingly urgent need to improve the existing classes of antifungals and to discover novel antifungals. Structural insights into drug targets and their complexes with both substrates and inhibitory ligands increase opportunity for the discovery of more effective antifungals. Implementation of this promise, which requires multiple skill sets, is beginning to yield candidates from discovery programs that could more quickly find their place in the clinic. This review will describe how structural biology is providing information for the improvement and discovery of inhibitors targeting the essential fungal enzyme sterol 14α-demethylase.

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Yang, Feng, Flora Teoh, Alrina Shin Min Tan, Yongbing Cao, Norman Pavelka, and Judith Berman. "Aneuploidy Enables Cross-Adaptation to Unrelated Drugs." Molecular Biology and Evolution 36, no. 8 (April 27, 2019): 1768–82. http://dx.doi.org/10.1093/molbev/msz104.

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AbstractAneuploidy is common both in tumor cells responding to chemotherapeutic agents and in fungal cells adapting to antifungal drugs. Because aneuploidy simultaneously affects many genes, it has the potential to confer multiple phenotypes to the same cells. Here, we analyzed the mechanisms by which Candida albicans, the most prevalent human fungal pathogen, acquires the ability to survive both chemotherapeutic agents and antifungal drugs. Strikingly, adaptation to both types of drugs was accompanied by the acquisition of specific whole-chromosome aneuploidies, with some aneuploid karyotypes recovered independently and repeatedly from very different drug conditions. Specifically, strains selected for survival in hydroxyurea, an anticancer drug, acquired cross-adaptation to caspofungin, a first-line antifungal drug, and both acquired traits were attributable to trisomy of the same chromosome: loss of trisomy was accompanied by loss of adaptation to both drugs. Mechanistically, aneuploidy simultaneously altered the copy number of most genes on chromosome 2, yet survival in hydroxyurea or caspofungin required different genes and stress response pathways. Similarly, chromosome 5 monosomy conferred increased tolerance to both fluconazole and to caspofungin, antifungals with different mechanisms of action. Thus, the potential for cross-adaptation is not a feature of aneuploidy per se; rather, it is dependent on specific genes harbored on given aneuploid chromosomes. Furthermore, pre-exposure to hydroxyurea increased the frequency of appearance of caspofungin survivors, and hydroxyurea-adapted C. albicans cells were refractory to antifungal drug treatment in a mouse model of systemic candidiasis. This highlights the potential clinical consequences for the management of cancer chemotherapy patients at risk of fungal infections.

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Kalola, Abhishek S., Shreya M. Shah, and Chirag B. Mistry. "Evaluation of prescription pattern of antifungal drugs in the dermatology department of a tertiary care teaching hospital." International Journal of Basic & Clinical Pharmacology 12, no. 3 (April 27, 2023): 427–33. http://dx.doi.org/10.18203/2319-2003.ijbcp20231123.

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Background: In general, fungal infections are one of the contributors of disease burden in the community, but irrational use of antifungal drugs can result in unwanted adverse events or antifungal drugs resistance. The present study was designed to analyze the prescription pattern of antifungal drugs prescribed in the dermatology department of a tertiary care teaching hospital. Methods: After getting permission from the ethics committee, this prospective observational cross-sectional study was conducted by analysis of prescriptions of 900 voluntary participant patients over a period of seven months in the dermatology outpatient department of a tertiary care teaching hospital in western India. Prescribed medicines’ parameters were analyzed as per WHO/INRUD prescription indicators. Results: Overall 900 prescriptions were analyzed, and among them around 50% patients were having tinea corporis and tinea cruris, making it the most common fungal infection. The most commonly prescribed antifungals were Clotrimazole (34.59%), followed by Fluconazole (31.61%) and Luliconazole (23.52%). Percentage of drugs prescribed from the WHO model list of essential medicines was 71.22%. Average number of antifungal drugs per prescription was 2.83 ± 0.57%. Conclusions: This study indicates prescribing practices of anti-fungal drugs and supportive medicines at tertiary care hospital that can be further improved by promoting prescribing by generic names. Overall final list of essential medicines at district level, state level and national level may vary as compared to the WHO list for anti-fungal drugs and doctors can consider alternative drugs as per domestic resistant pattern.

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Sharma, Jehoshua, Sierra Rosiana, Iqra Razzaq, and Rebecca Shapiro. "Linking Cellular Morphogenesis with Antifungal Treatment and Susceptibility in Candida Pathogens." Journal of Fungi 5, no. 1 (February 21, 2019): 17. http://dx.doi.org/10.3390/jof5010017.

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Fungal infections are a growing public health concern, and an increasingly important cause of human mortality, with Candida species being amongst the most frequently encountered of these opportunistic fungal pathogens. Several Candida species are polymorphic, and able to transition between distinct morphological states, including yeast, hyphal, and pseudohyphal forms. While not all Candida pathogens are polymorphic, the ability to undergo morphogenesis is linked with the virulence of many of these pathogens. There are also many connections between Candida morphogenesis and antifungal drug treatment and susceptibility. Here, we review how Candida morphogenesis—a key virulence trait—is linked with antifungal drugs and antifungal drug resistance. We highlight how antifungal therapeutics are able to modulate morphogenesis in both sensitive and drug-resistant Candida strains, the shared signaling pathways that mediate both morphogenesis and the cellular response to antifungal drugs and drug resistance, and the connection between Candida morphology, drug resistance, and biofilm growth. We further review the development of anti-virulence drugs, and targeting Candida morphogenesis as a novel therapeutic strategy to target fungal pathogens. Together, this review highlights important connections between fungal morphogenesis, virulence, and susceptibility to antifungals.

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Arastehfar, Amir, Toni Gabaldón, Rocio Garcia-Rubio, Jeffrey D. Jenks, Martin Hoenigl, Helmut J. F. Salzer, Macit Ilkit, Cornelia Lass-Flörl, and David S. Perlin. "Drug-Resistant Fungi: An Emerging Challenge Threatening Our Limited Antifungal Armamentarium." Antibiotics 9, no. 12 (December 8, 2020): 877. http://dx.doi.org/10.3390/antibiotics9120877.

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The high clinical mortality and economic burden posed by invasive fungal infections (IFIs), along with significant agricultural crop loss caused by various fungal species, has resulted in the widespread use of antifungal agents. Selective drug pressure, fungal attributes, and host- and drug-related factors have counteracted the efficacy of the limited systemic antifungal drugs and changed the epidemiological landscape of IFIs. Species belonging to Candida, Aspergillus, Cryptococcus, and Pneumocystis are among the fungal pathogens showing notable rates of antifungal resistance. Drug-resistant fungi from the environment are increasingly identified in clinical settings. Furthermore, we have a limited understanding of drug class-specific resistance mechanisms in emerging Candida species. The establishment of antifungal stewardship programs in both clinical and agricultural fields and the inclusion of species identification, antifungal susceptibility testing, and therapeutic drug monitoring practices in the clinic can minimize the emergence of drug-resistant fungi. New antifungal drugs featuring promising therapeutic profiles have great promise to treat drug-resistant fungi in the clinical setting. Mitigating antifungal tolerance, a prelude to the emergence of resistance, also requires the development of effective and fungal-specific adjuvants to be used in combination with systemic antifungals.

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Brunet, Kévin, Jean-Philippe Martellosio, Frédéric Tewes, Sandrine Marchand, and Blandine Rammaert. "Inhaled Antifungal Agents for Treatment and Prophylaxis of Bronchopulmonary Invasive Mold Infections." Pharmaceutics 14, no. 3 (March 14, 2022): 641. http://dx.doi.org/10.3390/pharmaceutics14030641.

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Pulmonary mold infections are life-threatening diseases with high morbi-mortalities. Treatment is based on systemic antifungal agents belonging to the families of polyenes (amphotericin B) and triazoles. Despite this treatment, mortality remains high and the doses of systemic antifungals cannot be increased as they often lead to toxicity. The pulmonary aerosolization of antifungal agents can theoretically increase their concentration at the infectious site, which could improve their efficacy while limiting their systemic exposure and toxicity. However, clinical experience is poor and thus inhaled agent utilization remains unclear in term of indications, drugs, and devices. This comprehensive literature review aims to describe the pharmacokinetic behavior and the efficacy of inhaled antifungal drugs as prophylaxes and curative treatments both in animal models and humans.

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김효진, 김기홍, and 박소희. "Systemic Antifungal Drugs for Onychomycosis." Korean Journal of Medical Mycology 21, no. 4 (December 2016): 105–10. http://dx.doi.org/10.17966/kjmm.2016.21.4.105.

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Nishimoto, Katsutaro. "Antifungal Drugs for Pediatric Use." Nippon Ishinkin Gakkai Zasshi 40, no. 3 (1999): 125–28. http://dx.doi.org/10.3314/jjmm.40.125.

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O??Day, Denis M. "New Antifungal Drugs in Ophthalmology." International Ophthalmology Clinics 36, no. 2 (1996): 45–51. http://dx.doi.org/10.1097/00004397-199603620-00006.

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Stylianou, Marios, Evgeny Kulesskiy, José Pedro Lopes, Margareta Granlund, Krister Wennerberg, and Constantin F. Urban. "Antifungal Application of Nonantifungal Drugs." Antimicrobial Agents and Chemotherapy 58, no. 2 (November 25, 2013): 1055–62. http://dx.doi.org/10.1128/aac.01087-13.

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ABSTRACTCandidaspecies are the cause of 60% of all mycoses in immunosuppressed individuals, leading to ∼150,000 deaths annually due to systemic infections, whereas the current antifungal therapies either have toxic side effects or are insufficiently efficient. We performed a screening of two compound libraries, the Enzo and the Institute for Molecular Medicine Finland (FIMM) oncology collection library, for anti-Candidaactivity based on the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. From a total of 844 drugs, 26 agents showed activity againstCandida albicans. Of those, 12 were standard antifungal drugs (SADs) and 7 were off-target drugs previously reported to be active againstCandidaspp. The remaining 7 off-target drugs, amonafide, tosedostat, megestrol acetate, melengestrol acetate, stanozolol, trifluperidol, and haloperidol, were identified with this screen. The anti-Candidaactivities of the new agents were investigated by three individual assays using optical density, ATP levels, and microscopy. The antifungal activities of these drugs were comparable to those of the SADs found in the screen. The aminopeptidase inhibitor tosedostat, which is currently in a clinical trial phase for anticancer therapy, displayed a broad antifungal activity against differentCandidaspp., includingCandida glabrata. Thus, this screen reveals agents that were previously unknown to be anti-Candidaagents, which allows for the design of novel therapies against invasive candidiasis.

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Davey, P. G. "New antiviral and antifungal drugs." BMJ 300, no. 6727 (March 24, 1990): 793–98. http://dx.doi.org/10.1136/bmj.300.6727.793.

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Hay, Roderick J. "Antifungal drugs on the horizon." Journal of the American Academy of Dermatology 31, no. 3 (September 1994): S82—S86. http://dx.doi.org/10.1016/s0190-9622(08)81275-3.

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Aparicio, Jesús F. "Generating Novel Polyene Antifungal Drugs." Chemistry & Biology 12, no. 5 (May 2005): 509–10. http://dx.doi.org/10.1016/j.chembiol.2005.05.002.

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Afeltra, J., and P. E. Verweij. "Antifungal Activity of Nonantifungal Drugs." European Journal of Clinical Microbiology & Infectious Diseases 22, no. 7 (July 1, 2003): 397–407. http://dx.doi.org/10.1007/s10096-003-0947-x.

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Odds, Frank C. "New approaches for antifungal drugs." Trends in Microbiology 1, no. 6 (September 1993): 246–47. http://dx.doi.org/10.1016/0966-842x(93)90142-e.

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YAMAGUCHI, HIDEYO, SHIGERU ABE, and YOSHIKO TOKUDA. "Immunomodulating Activity of Antifungal Drugs." Annals of the New York Academy of Sciences 685, no. 1 Immunomodulat (June 1993): 447–57. http://dx.doi.org/10.1111/j.1749-6632.1993.tb35905.x.

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Nix, David E. "Cardiotoxicity Induced by Antifungal Drugs." Current Fungal Infection Reports 8, no. 2 (April 6, 2014): 129–38. http://dx.doi.org/10.1007/s12281-014-0183-0.

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Serena, Carolina, Francisco Javier Pastor, Montserrat Ortoneda, Javier Capilla, Nicole Nolard, and Josep Guarro. "In Vitro Antifungal Susceptibilities of Uncommon Basidiomycetous Yeasts." Antimicrobial Agents and Chemotherapy 48, no. 7 (July 2004): 2724–26. http://dx.doi.org/10.1128/aac.48.7.2724-2726.2004.

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ABSTRACT The in vitro activities of eight antifungal drugs against 50 isolates of basidiomycetous yeasts were determined by a microdilution method. In general fluconazole and micafungin were inactive. Terbinafine was active only against Sporobolomyces salmonicolor. The activities of the other antifungals were variable and depended on the species tested. The new triazoles showed the lowest MICs, but amphotericin B and itraconazole were the only drugs active against Cryptococcus albidus.

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Jha, Anubhuti, and Awanish Kumar. "Anticandidal agent for multiple targets: the next paradigm in the discovery of proficient therapeutics/overcoming drug resistance." Future Medicinal Chemistry 11, no. 22 (November 2019): 2955–74. http://dx.doi.org/10.4155/fmc-2018-0479.

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Candida albicans is a prominent human fungal pathogen. Current treatments are suffering a massive gap due to emerging resistance against available antifungals. Therefore, there is an ardent need for novel antifungal candidates that essentially have more than one target, as most antifungal repertoires are single-target drugs. Exploration of multiple-drug targeting in antifungal therapeutics is still pending. An extensive literature survey was performed to categorize and comprehend relevant studies and the current therapeutic scenario that led researchers to preferentially consider multitarget drug-based Candida infection therapy. With this article, we identified and compiled a few potent antifungal compounds that are directed toward multiple virulent targets in C. albicans. Such compound(s) provide an optimistic platform of multiple targeting and could leave a substantial impact on the development of effective antifungals.

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Prasad, Rajendra, Atanu Banerjee, and Abdul Haseeb Shah. "Resistance to antifungal therapies." Essays in Biochemistry 61, no. 1 (February 28, 2017): 157–66. http://dx.doi.org/10.1042/ebc20160067.

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The evolution of antifungal resistance among fungal pathogens has rendered the limited arsenal of antifungal drugs futile. Considering the recent rise in the number of nosocomial fungal infections in immunocompromised patients, the emerging clinical multidrug resistance (MDR) has become a matter of grave concern for medical professionals. Despite advances in therapeutic interventions, it has not yet been possible to devise convincing strategies to combat antifungal resistance. Comprehensive understanding of the molecular mechanisms of antifungal resistance is essential for identification of novel targets that do not promote or delay emergence of drug resistance. The present study discusses features and limitations of the currently available antifungals, mechanisms of antifungal resistance and highlights the emerging therapeutic strategies that could be deployed to combat MDR.

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Fernández-Torres, B., A. J. Carrillo, E. Martı́n, A. Del Palacio, M. K. Moore, A. Valverde, M. Serrano, and J. Guarro. "In Vitro Activities of 10 Antifungal Drugs against 508 Dermatophyte Strains." Antimicrobial Agents and Chemotherapy 45, no. 9 (September 1, 2001): 2524–28. http://dx.doi.org/10.1128/aac.45.9.2524-2528.2001.

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ABSTRACT We have tested 508 strains belonging to 24 species of dermatophytes against 10 antifungal drugs following mainly the NCCLS (M38-P) standard for filamentous fungi. However, several important factors, such as the temperature (28 versus 35°C) and time of incubation (4 to 10 days versus 21 to 74 h), have been modified. The antifungals used were itraconazole, ketoconazole, miconazole, clotrimazole, voriconazole, terbinafine, amphotericin B, fluconazole, UR-9825, and G-1. In general, with the exception of fluconazole and G-1, all antifungals were shown to be highly effective.

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Fernandes, Chantal, Rafael Prados-Rosales, Branca M. A. Silva, Antonio Nakouzi-Naranjo, Mónica Zuzarte, Subhasish Chatterjee, Ruth E. Stark, Arturo Casadevall, and Teresa Gonçalves. "Activation of Melanin Synthesis in Alternaria infectoria by Antifungal Drugs." Antimicrobial Agents and Chemotherapy 60, no. 3 (December 28, 2015): 1646–55. http://dx.doi.org/10.1128/aac.02190-15.

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The importance ofAlternariaspecies fungi to human health ranges from their role as etiological agents of serious infections with poor prognoses in immunosuppressed individuals to their association with respiratory allergic diseases. The present work focuses onAlternaria infectoria, which was used as a model organism of the genus, and was designed to unravel melanin production in response to antifungals. After we characterized the pigment produced byA. infectoria, we studied the dynamics of 1,8-dihydroxynaphthalene (DHN)-melanin production during growth, the degree of melanization in response to antifungals, and how melanization affected susceptibility to several classes of therapeutic drugs. We demonstrate thatA. infectoriaincreased melanin deposition in cell walls in response to nikkomycin Z, caspofungin, and itraconazole but not in response to fluconazole or amphotericin B. These results indicate thatA. infectoriaactivates DHN-melanin synthesis in response to certain antifungal drugs, possibly as a protective mechanism against these drugs. Inhibition of DHN-melanin synthesis by pyroquilon resulted in a lower minimum effective concentration (MEC) of caspofungin and enhanced morphological changes (increased hyphal balloon size), characterized by thinner and less organizedA. infectoriacell walls. In summary,A. infectoriasynthesizes melanin in response to certain antifungal drugs, and its susceptibility is influenced by melanization, suggesting the therapeutic potential of drug combinations that affect melanin synthesis.

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Journal articles on the topic 'Antifungal drugs'

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