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1

Meletiadis, Joseph, Saigh Rafal Al, Aristea Velegraki, Thomas Walsh, Emmanuel Roilides, and Loukia Zerva. "Pharmacodynamic Effects of Simulated Standard Doses of Antifungal Drugs against Aspergillus Species in a New In Vitro Pharmacokinetic/Pharmacodynamic Model." Antimicrobial agents and chemotherapy 56, no. 11 (2011): 403–10. https://doi.org/10.1128/AAC.00662-11.

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In conventional MIC tests, fungi are exposed to constant drug concentrations, whereas in vivo, fungi are exposed to changing drug concentrations. Therefore, we developed a new in vitro pharmacokinetic/pharmacodynamic model where human plasma pharmacokinetics of standard doses of 1 mg/kg amphotericin B, 4 mg/kg voriconazole, and 1 mg/kg caspofungin were simulated and their pharmacodynamic characteristics were determined against three clinical isolates of Aspergillus fumigatus, Aspergillus flavus, and Aspergillus terreus with identical MICs (1 mg/liter for amphotericin B, 0.5 mg/liter for vorico
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2

Begum, Jubeda, and P. Das. "Antifungal resistance in dermatophytosis: A global health concern." Letters In Animal Biology 2, no. 1 (2022): 41–45. http://dx.doi.org/10.62310/liab.v2i1.76.

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Dermatophytosis is a common dermatological problem in animals as well as humans which is associated with interference in immune function. Unlike the antibacterial resistance which is frequently reported, antifungal resistance is less commonly reported, but there are reports of emerging antifungal resistance in humans and animals. The problem of antifungal resistance can be more severe in comparison to any other drug resistance due to the limited number of antifungals available for therapeutic purpose. A number of mechanisms have been put forward to explain the phenomenon of antifungal drug res
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Mandal, Debashree. "Evaluating the Impact of Antifungal Drugs on Human Health and Exploring Alternative Treatments." Oriental Journal Of Chemistry 40, no. 3 (2024): 630–45. http://dx.doi.org/10.13005/ojc/400302.

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Fungi occurred naturally like Candida yeast, in the human body. It may grow on skin, inside the digestive system and vagina. Antifungal drugs are used to kill or stop this fungal growth. According to their mode of action they are divided into azoles (inhibit ergosterol synthesis), echinocandins (damage cell walls), and polyenes (destroy fungal cells) etc. Depending on the seriousness of infection and type of infection, generally antifungal drugs are administered to a body. Oral antifungals are taken by mouth for systemic infections. Topical antifungals (creams, ointments) treat localized skin
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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 (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 d
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Arastehfar, Amir, Toni Gabaldón, Rocio Garcia-Rubio, et al. "Drug-Resistant Fungi: An Emerging Challenge Threatening Our Limited Antifungal Armamentarium." Antibiotics 9, no. 12 (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 f
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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 (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
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7

Gunawan, Untung, Slamet Ibrahim, Atthar Luqman Ivansyah, and Sophi Damayanti. "Separation and analysis of triazole antifungal in biological matrices by liquid chromatography: a review." Pharmacia 70, no. 4 (2023): 1265–81. http://dx.doi.org/10.3897/pharmacia.70.e111511.

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Invasive fungal infections cause serious illness and death worldwide. Long-term therapeutic and preventative use of antifungal drugs in high-risk patients has caused resistance. Triazole antifungals are widely used to prevent and treat fungal infections, and therapeutic drug monitoring has been suggested to improve outcomes, reduce toxicity, and prevent drug resistance. Common methods used for monitoring triazole antifungal drugs in biological matrices such as blood, serum, and plasma include bioassay and instrumentation methods, especially liquid chromatography. Sample preparation is needed t
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8

Gunawan, Untung, Slamet Ibrahim, Atthar Luqman Ivansyah, and Sophi Damayanti. "Separation and analysis of triazole antifungal in biological matrices by liquid chromatography: a review." Pharmacia 70, no. (4) (2023): 1265–81. https://doi.org/10.3897/pharmacia.70.e111511.

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Invasive fungal infections cause serious illness and death worldwide. Long-term therapeutic and preventative use of antifungal drugs in high-risk patients has caused resistance. Triazole antifungals are widely used to prevent and treat fungal infections, and therapeutic drug monitoring has been suggested to improve outcomes, reduce toxicity, and prevent drug resistance. Common methods used for monitoring triazole antifungal drugs in biological matrices such as blood, serum, and plasma include bioassay and instrumentation methods, especially liquid chromatography. Sample preparation is needed t
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9

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 (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
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10

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 (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 trea
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11

Leung, Ryan Y. H., and Jimmy Y. W. Lam. "The Patterns and Appropriateness of Systemic Antifungal Prescriptions in a Regional Hospital in Hong Kong." Antibiotics 14, no. 6 (2025): 556. https://doi.org/10.3390/antibiotics14060556.

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Introduction: The consumption of systemic antifungals is on the rise. However, a significant proportion of systemic antifungal prescriptions is inappropriate. Inappropriately prescribed antifungals are problematic, but there has been minimal emphasis on ensuring the appropriate prescription of systemic antifungals. Local studies regarding the patterns and appropriateness of antifungal prescriptions are also lacking. Materials and Methods: In this retrospective, single-centre, observational study, every in-patient prescription order of systemic antifungals in a regional hospital in Hong Kong be
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12

Carmo, Anália, Marilia Rocha, Patricia Pereirinha, Rui Tomé, and Eulália Costa. "Antifungals: From Pharmacokinetics to Clinical Practice." Antibiotics 12, no. 5 (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 rout
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13

Wall, Gina, and Jose L. Lopez-Ribot. "Current Antimycotics, New Prospects, and Future Approaches to Antifungal Therapy." Antibiotics 9, no. 8 (2020): 445. http://dx.doi.org/10.3390/antibiotics9080445.

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Fungal infections represent an increasing threat to a growing number of immune- and medically compromised patients. Fungi are eukaryotic organisms and, as such, there is a limited number of selective targets that can be exploited for antifungal drug development. This has also resulted in a very restricted number of antifungal drugs that are clinically available for the treatment of invasive fungal infections at the present time—polyenes, azoles, echinocandins, and flucytosine. Moreover, the utility of available antifungals is limited by toxicity, drug interactions and the emergence of resistan
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14

Monk, Brian C., та Mikhail V. Keniya. "Roles for Structural Biology in the Discovery of Drugs and Agrochemicals Targeting Sterol 14α-Demethylases". Journal of Fungi 7, № 2 (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 yiel
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15

Jay, Shah. "Drug Prescribing Pattern of Antifungal Drugs for Local Fungal Infections at a Tertiary Care Hospital, Palanpur, Gujarat." International Journal of Pharmaceutical and Clinical Research 14, no. 9 (2022): 88–93. https://doi.org/10.5281/zenodo.13323564.

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<strong>Aim:&nbsp;</strong>Present research was performed to know the pattern of dermatological diseases in this area and to study the prescription pattern of antifungals in this organization.&nbsp;<strong>Material and Methods</strong><strong>:</strong>&nbsp;Present research was performed at Banas Medical College And Research Institute, Palanpur, Gujarat. Data of drugs prescribed were taken from subject&rsquo;s prescription. Prescriptions incorporated all recently diagnosed subjects with cutaneous fungal infection of both genders who attended Dermatology OPD. Factors measured were sociodemogra
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16

Bouz, Ghada, and Martin Doležal. "Advances in Antifungal Drug Development: An Up-To-Date Mini Review." Pharmaceuticals 14, no. 12 (2021): 1312. http://dx.doi.org/10.3390/ph14121312.

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The utility of clinically available antifungals is limited by their narrow spectrum of activity, high toxicity, and emerging resistance. Antifungal drug discovery has always been a challenging area, since fungi and their human host are eukaryotes, making it difficult to identify unique targets for antifungals. Novel antifungals in clinical development include first-in-class agents, new structures for an established target, and formulation modifications to marketed antifungals, in addition to repurposed agents. Membrane interacting peptides and aromatherapy are gaining increased attention in th
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17

Giordano, Ana Luisa Perini Leme, Marili Villa Nova Rodrigues, Karen Gabriela Araujo dos Santos, et al. "Enhancing Antifungal Drug Discovery Through Co-Culture with Antarctic Streptomyces albidoflavus Strain CBMAI 1855." International Journal of Molecular Sciences 25, no. 23 (2024): 12744. http://dx.doi.org/10.3390/ijms252312744.

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Fungal infections pose a growing public health threat, creating an urgent clinical need for new antifungals. Natural products (NPs) from organisms in extreme environments are a promising source for novel drugs. Streptomyces albidoflavus CBMAI 1855 exhibited significant potential in this regard. This study aimed to (1) assess the antifungal spectrum of the CBMAI 1855 extract against key human pathogens, (2) elicit NP production through co-cultivation with fungi, correlating the metabolites with the biosynthetic gene clusters (BGCs), and (3) perform in silico toxicity predictions of the identifi
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18

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 (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
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Mathew, Sherin, Cristy Anne Kuriakose, Sandra Shaji, Binu Upendran, and Lakshmi R. "Drug Utilization Evaluation of Systemic Antifungals in a Tertiary Care Hospital." Saudi Journal of Medical and Pharmaceutical Sciences 9, no. 09 (2023): 684–92. http://dx.doi.org/10.36348/sjmps.2023.v09i09.012.

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Introduction: The incidence of Invasive Fungal Infection has increased, and it constitutes a serious threat to human health and life, especially in immunocompromised and critically ill patients. We aimed to evaluate the appropriateness of antifungal agents along with their risk factors and sensitivity pattern. Methods: It is a retrospective, cross-sectional study, which includes details of patients prescribed with systemic antifungal agents during a period of five years (01-06-2016 to 31-05-2021). Collected details were compared with Infectious Diseases Society of America (IDSA) guidelines and
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Vahedi-Shahandashti, Roya, and Cornelia Lass-Flörl. "Novel Antifungal Agents and Their Activity against Aspergillus Species." Journal of Fungi 6, no. 4 (2020): 213. http://dx.doi.org/10.3390/jof6040213.

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There is a need for new antifungal agents, mainly due to increased incidence of invasive fungal infections (IFI), high frequency of associated morbidity and mortality and limitations of the current antifungal agents (e.g., toxicity, drug–drug interactions, and resistance). The clinically available antifungals for IFI are restricted to four main classes: polyenes, flucytosine, triazoles, and echinocandins. Several antifungals are hampered by multiple resistance mechanisms being present in fungi. Consequently, novel antifungal agents with new targets and modified chemical structures are required
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Patra, Sandip, Mayur Raney, Aditi Pareek, and Rupinder Kaur. "Epigenetic Regulation of Antifungal Drug Resistance." Journal of Fungi 8, no. 8 (2022): 875. http://dx.doi.org/10.3390/jof8080875.

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In medical mycology, epigenetic mechanisms are emerging as key regulators of multiple aspects of fungal biology ranging from development, phenotypic and morphological plasticity to antifungal drug resistance. Emerging resistance to the limited therapeutic options for the treatment of invasive fungal infections is a growing concern. Human fungal pathogens develop drug resistance via multiple mechanisms, with recent studies highlighting the role of epigenetic changes involving the acetylation and methylation of histones, remodeling of chromatin and heterochromatin-based gene silencing, in the ac
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Chai, Shuang, Jing-Lun Zhan, Li-Mei Zhao, and Xiao-Dong Liu. "Safety of triazole antifungals: a pharmacovigilance study from 2004 to 2021 based on FAERS." Therapeutic Advances in Drug Safety 13 (January 2022): 204209862211432. http://dx.doi.org/10.1177/20420986221143266.

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Background: Triazole antifungals are widely used as broad-spectrum antifungal activity; however, there are many undetected and unreported adverse events (AEs). Methods: Data from the Food and Drug Administration Adverse Event Reporting System (FAERS) from the first quarter (Q1) of 2004 to the third quarter (Q3) of 2021 were selected for disproportionality analysis to assess the connection between antifungal triazoles, and AEs and important medical events (IMEs). Results: A total of 22,566 records associated with triazole antifungals were identified, with 9584 triazole antifungal–IME pairs. The
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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 (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
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Kabir, Md Saiful, Wazeda Begum, Md Maruf Ur Rahman, and Nehal Warish. "A case report of drug resistant Tinea corporis." Journal of Dhaka National Medical College & Hospital 24, no. 1 (2018): 44–47. https://doi.org/10.3329/jdnmch.v24i1.80058.

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Superfecial fungal infections of the skin are a major health problem and associated with morbidity due to chronic itching and inflammation of skin. Tinea corporis is known as ringworm, a superficial fungal infection (dermatophytosis) of the arms and legs, especially on glabrous skin. Treatment includes systemic and topical antifungals with variable duration depending upon the site of infection and the antifungal chosen. Choosing the right treatment is not always simple because of the possibility of drug interactions and drug resistance. Recently Clinical failure and relapses have been observed
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Prasad, Rajendra, Atanu Banerjee, and Abdul Haseeb Shah. "Resistance to antifungal therapies." Essays in Biochemistry 61, no. 1 (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 no
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Horn, Connor, та Govindsamy Vediyappan. "Anticapsular and Antifungal Activity of α-Cyperone". Antibiotics 10, № 1 (2021): 51. http://dx.doi.org/10.3390/antibiotics10010051.

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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 dr
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Parente-Rocha, Juliana Alves, Alexandre Melo Bailão, André Correa Amaral, et al. "Antifungal Resistance, Metabolic Routes as Drug Targets, and New Antifungal Agents: An Overview about Endemic Dimorphic Fungi." Mediators of Inflammation 2017 (2017): 1–16. http://dx.doi.org/10.1155/2017/9870679.

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Diseases caused by fungi can occur in healthy people, but immunocompromised patients are the major risk group for invasive fungal infections. Cases of fungal resistance and the difficulty of treatment make fungal infections a public health problem. This review explores mechanisms used by fungi to promote fungal resistance, such as the mutation or overexpression of drug targets, efflux and degradation systems, and pleiotropic drug responses. Alternative novel drug targets have been investigated; these include metabolic routes used by fungi during infection, such as trehalose and amino acid meta
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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 (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 drug
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Forastiero, A., A. C. Mesa-Arango, A. Alastruey-Izquierdo, et al. "Candida tropicalis Antifungal Cross-Resistance Is Related to Different Azole Target (Erg11p) Modifications." Antimicrobial Agents and Chemotherapy 57, no. 10 (2013): 4769–81. http://dx.doi.org/10.1128/aac.00477-13.

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ABSTRACTCandida tropicalisranks between third and fourth amongCandidaspecies most commonly isolated from clinical specimens. Invasive candidiasis and candidemia are treated with amphotericin B or echinocandins as first-line therapy, with extended-spectrum triazoles as acceptable alternatives.Candida tropicalisis usually susceptible to all antifungal agents, although several azole drug-resistant clinical isolates are being reported. However,C. tropicalisresistant to amphotericin B is uncommon, and only a few strains have reliably demonstrated a high level of resistance to this agent. The resist
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Addetla, Sagarika* Boreda Sowmya Aprajitha Bhatnagar Dr. Kameswari. "FLUCONAZOLE: A REVIEW." Indo American Journal of Pharmaceutical Sciences (IAJPS) 03, no. 09 (2016): 1004–8. https://doi.org/10.5281/zenodo.154436.

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Fluconazole is a bis-triazole antifungal drug with novel pharmacokinetic properties (metabolic stability, relatively high water solubility) which contribute to its therapeutic activity. Fluconazole is a medication that is given either by mouth or intravenously. It is used to treat a variety of fungal infections, especially Candida infections of the vagina (yeast infections), mouth, throat, and bloodstream. This article describes about the uses of fluconazole drug in immunocompromised patients and in the treatment of other fungal infections. Fungal resistance to drugs in the azole class tends t
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Saunders, Jacqueline, Kayla Maki, Renee Koski, and S. Eric Nybo. "Tavaborole, Efinaconazole, and Luliconazole: Three New Antimycotic Agents for the Treatment of Dermatophytic Fungi." Journal of Pharmacy Practice 30, no. 6 (2016): 621–30. http://dx.doi.org/10.1177/0897190016660487.

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Fungal diseases of the nail bed (onychomycosis) and epidermis are recurrent illnesses in the elderly and immunocompromised patients, which have few efficacious treatment options. Current treatment options for onychomycosis are limited to topical agents, laser treatment, and oral antifungals. Previous generations of topical agents were not efficacious, owing to poor penetration of the nail bed. Oral antifungal drugs, such as itraconazole, terbinafine, and fluconazole, not only give better response rates but also inhibit a host of CYP450 enzymes. Oral antifungals can exacerbate drug–drug interac
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Zhou, Yue, and Todd B. Reynolds. "Innovations in Antifungal Drug Discovery among Cell Envelope Synthesis Enzymes through Structural Insights." Journal of Fungi 10, no. 3 (2024): 171. http://dx.doi.org/10.3390/jof10030171.

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Life-threatening systemic fungal infections occur in immunocompromised patients at an alarming rate. Current antifungal therapies face challenges like drug resistance and patient toxicity, emphasizing the need for new treatments. Membrane-bound enzymes account for a large proportion of current and potential antifungal targets, especially ones that contribute to cell wall and cell membrane biosynthesis. Moreover, structural biology has led to a better understanding of the mechanisms by which these enzymes synthesize their products, as well as the mechanism of action for some antifungals. This r
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Parslow, Ben Y., and Christopher R. Thornton. "Continuing Shifts in Epidemiology and Antifungal Susceptibility Highlight the Need for Improved Disease Management of Invasive Candidiasis." Microorganisms 10, no. 6 (2022): 1208. http://dx.doi.org/10.3390/microorganisms10061208.

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Invasive candidiasis (IC) is a systemic life-threatening infection of immunocompromised humans, but remains a relatively neglected disease among public health authorities. Ongoing assessments of disease epidemiology are needed to identify and map trends of importance that may necessitate improvements in disease management and patient care. Well-established incidence increases, largely due to expanding populations of patients with pre-disposing risk factors, has led to increased clinical use and pressures on antifungal drugs. This has been exacerbated by a lack of fast, accurate diagnostics tha
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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 (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
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Ghannoum, Mahmoud A., and Louis B. Rice. "Antifungal Agents: Mode of Action, Mechanisms of Resistance, and Correlation of These Mechanisms with Bacterial Resistance." Clinical Microbiology Reviews 12, no. 4 (1999): 501–17. http://dx.doi.org/10.1128/cmr.12.4.501.

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SUMMARY The increased use of antibacterial and antifungal agents in recent years has resulted in the development of resistance to these drugs. The significant clinical implication of resistance has led to heightened interest in the study of antimicrobial resistance from different angles. Areas addressed include mechanisms underlying this resistance, improved methods to detect resistance when it occurs, alternate options for the treatment of infections caused by resistant organisms, and strategies to prevent and control the emergence and spread of resistance. In this review, the mode of action
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Firacative, Carolina. "ANTIFUNGAL RESISTANCE: A GROWING CONCERN." Acta Biológica Colombiana 28, no. 3 (2023): 368–75. http://dx.doi.org/10.15446/abc.v28n3.104736.

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Globally, the increasing number of drug-resistant human pathogens represents a major threat to public health. Among these pathogens, fungi that have acquired resistance to the already scarce arsenal of antifungals are of particular significance, as they present therapeutic challenges that increase morbidity and mortality rates. Particularly, most mycoses are opportunistic since they mainly affect hosts with a weakened immune system, including patients with cancer, hematological malignancies, prolonged neutropenia, solid organ transplants, HIV/AIDS, patients in intensive care units, using centr
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Fang, Yue, Lingling Hu, Xin Zhou, et al. "A Genomewide Screen in Schizosaccharomyces pombe for Genes Affecting the Sensitivity of Antifungal Drugs That Target Ergosterol Biosynthesis." Antimicrobial Agents and Chemotherapy 56, no. 4 (2012): 1949–59. http://dx.doi.org/10.1128/aac.05126-11.

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ABSTRACTWe performed a genomewide screen for altered sensitivity to antifungal drugs, including clotrimazole and terbinafine, that target ergosterol biosynthesis using aSchizosaccharomyces pombegene deletion library consisting of 3,004 nonessential haploid deletion mutants. We identified 109 mutants that were hypersensitive and 11 mutants that were resistant to these antifungals. Proteins whose absence rendered cells sensitive to these antifungals were classified into various functional categories, including ergosterol biosynthesis, membrane trafficking, histone acetylation and deacetylation,
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Kim, Jong H., Luisa W. Cheng, Kathleen L. Chan, et al. "Antifungal Drug Repurposing." Antibiotics 9, no. 11 (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 tebuconaz
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Hassoun, Nesrine, Issmat I. Kassem, Monzer Hamze, Jad El Tom, Nicolas Papon, and Marwan Osman. "Antifungal Use and Resistance in a Lower–Middle-Income Country: The Case of Lebanon." Antibiotics 12, no. 9 (2023): 1413. http://dx.doi.org/10.3390/antibiotics12091413.

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Antimicrobial resistance is a serious threat, particularly in low- and middle-income countries (LMICs). Antifungal resistance is often underestimated in both healthcare and non-clinical settings. In LMICs, it is believed that the inappropriate use of antifungals, limited surveillance systems, and low diagnostic capacities are significant drivers of resistance. Like other LMICs, Lebanon lacks antifungal use and resistance surveillance programs, and the impact of antifungal resistance in the country remains unclear, especially during the unfolding economic crisis that has severely affected medic
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Tome, Miha, Jure Zupan, Zorica Tomičić, Tadeja Matos, and Peter Raspor. "Synergistic and antagonistic effects of immunomodulatory drugs on the action of antifungals againstCandida glabrataandSaccharomyces cerevisiae." PeerJ 6 (June 13, 2018): e4999. http://dx.doi.org/10.7717/peerj.4999.

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Candidemia and other forms of invasive fungal infections caused byCandida glabrataand to a lesser extentSaccharomyces cerevisiaeare a serious health problem, especially if their steadily rising resistance to the limited range of antifungal drugs is taken into consideration. Various drug combinations are an attractive solution to the resistance problem, and some drug combinations are already common in the clinical environment due to the nature of diseases or therapies. We tested a few of the common antifungal-immunomodulatory drug combinations and evaluated their effect on selected strains ofC.
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MARIAN, Mariana, and Mihai MAREȘ. "TARGETING IRON ACQUISITION MECHANISMS OF INVASIVE FUNGAL INFECTIONS: OLD AND NEW INSIGHTS." Scientific Papers Journal VETERINARY SERIES 67, no. 3 (2024): 36–42. https://doi.org/10.61900/spjvs.2024.03.05.

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The development of antifungal drugs encounters a significant challenge due to the close phylogenetic relationship between fungi and mammals, both being eukaryotic organisms that share many similar cellular and molecular processes. The toxicity of antifungal compounds is bilaterally distributed, complicating the development of highly selective therapeutic agents. The four classes of antifungals for treating invasive fungal infections—polyene macrolides, azoles, pyrimidine analogs, and echinocandins—offer therapeutic benefits but also have limitations regarding their spectrum of activity, route
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Bugli, Francesca, Brunella Posteraro, Massimiliano Papi, et al. "In VitroInteraction between Alginate Lyase and Amphotericin B against Aspergillus fumigatus Biofilm Determined by Different Methods." Antimicrobial Agents and Chemotherapy 57, no. 3 (2012): 1275–82. http://dx.doi.org/10.1128/aac.01875-12.

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ABSTRACTAspergillus fumigatusbiofilms represent a problematic clinical entity, especially because of their recalcitrance to antifungal drugs, which poses a number of therapeutic implications for invasive aspergillosis, the most difficult-to-treatAspergillus-related disease. While the antibiofilm activities of amphotericin B (AMB) deoxycholate and its lipid formulations (e.g., liposomal AMB [LAMB]) are well documented, the effectiveness of these drugs in combination with nonantifungal agents is poorly understood. In the present study,in vitrointeractions between polyene antifungals (AMB and LAM
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Fernandes, Chantal, Rafael Prados-Rosales, Branca M. A. Silva, et al. "Activation of Melanin Synthesis in Alternaria infectoria by Antifungal Drugs." Antimicrobial Agents and Chemotherapy 60, no. 3 (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 t
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Yamin, Dina, Mutiat Hammed Akanmu, Abbas Al Mutair, Saad Alhumaid, Ali A. Rabaan, and Khalid Hajissa. "Global Prevalence of Antifungal-Resistant Candida parapsilosis: A Systematic Review and Meta-Analysis." Tropical Medicine and Infectious Disease 7, no. 8 (2022): 188. http://dx.doi.org/10.3390/tropicalmed7080188.

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A reliable estimate of Candida parapsilosis antifungal susceptibility in candidemia patients is increasingly important to track the spread of C. parapsilosis bloodstream infections and define the true burden of the ongoing antifungal resistance. A systematic review and meta-analysis (SRMA) were conducted aiming to estimate the global prevalence and identify patterns of antifungal resistance. A systematic literature search of the PubMed, Scopus, ScienceDirect and Google Scholar electronic databases was conducted on published studies that employed antifungal susceptibility testing (AFST) on clin
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Amich, Jorge. "Sulfur Metabolism as a Promising Source of New Antifungal Targets." Journal of Fungi 8, no. 3 (2022): 295. http://dx.doi.org/10.3390/jof8030295.

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Fungal infections are a growing threat to human health. Despite their clinical relevance, there is a surprisingly limited availability of clinically approved antifungal agents, which is seriously aggravated by the recent appearance and fast spread of drug resistance. It is therefore clear that there is an urgent need for novel and efficient antifungals. In this context, metabolism is recognized as a promising source for new antifungal targets and, indeed, there are new drugs in development that target metabolic pathways. Fungal sulfur metabolism is particularly interesting, as many of its proc
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NIWA, Toshiro, Toshifumi SHIRAGA, and Akira TAKAGI. "Drug-Drug Interaction of Antifungal Drugs." YAKUGAKU ZASSHI 125, no. 10 (2005): 795–805. http://dx.doi.org/10.1248/yakushi.125.795.

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Hameed, Saif, and Zeeshan Fatima. "Novel Regulatory Mechanisms of Pathogenicity and Virulence to Combat MDR inCandida albicans." International Journal of Microbiology 2013 (2013): 1–10. http://dx.doi.org/10.1155/2013/240209.

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Continuous deployment of antifungals in treating infections caused by dimorphic opportunistic pathogenCandida albicanshas led to the emergence of drug resistance resulting in cross-resistance to many unrelated drugs, a phenomenon termed multidrug resistance (MDR). Despite the current understanding of major factors which contribute to MDR mechanisms, there are many lines of evidence suggesting that it is a complex interplay of multiple factors which may be contributed by still unknown mechanisms. Coincidentally with the increased usage of antifungal drugs, the number of reports for antifungal d
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Schinas, Georgios, Nikolaos Spernovasilis, and Karolina Akinosoglou. "Antifungal pipeline: Is there light at the end of the tunnel?" World Journal of Clinical Cases 12, no. 16 (2024): 2686–91. http://dx.doi.org/10.12998/wjcc.v12.i16.2686.

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The misuse and overuse of classic antifungals have accelerated the development of resistance mechanisms, diminishing the efficacy of established therapeutic pathways and necessitating a shift towards alternative targets. Despite this pressing need for new treatments, the antifungal drug pipeline has been largely stagnant for the past three decades, primarily due to the high risks and costs associated with antifungal drug development, compounded by uncertain market returns. Extensive research durations, special patient populations and rigorous regulatory demands pose significant barriers to bri
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Biersack, Bernhard. "The Antifungal Potential of Niclosamide and Structurally Related Salicylanilides." International Journal of Molecular Sciences 25, no. 11 (2024): 5977. http://dx.doi.org/10.3390/ijms25115977.

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Human mycoses cover a diverse field of fungal diseases from skin disorders to systemic invasive infections and pose an increasing global health problem based on ineffective treatment options, the hampered development of new efficient drugs, and the emergence of resistant fungal strains. Niclosamide is currently applied for the treatment of worm infections. Its mechanisms of action, which include the suppression of mitochondrial oxidative phosphorylation (also known as mitochondrial uncoupling), among others, has led to a repurposing of this promising anthelmintic drug for the therapy of furthe
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50

Perfect, John R. "Molecular targets for new antifungal drugs." Canadian Journal of Botany 73, S1 (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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