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Green Nanoparticles
Published in Richard L. K. Glover, Daniel Nyanganyura, Rofhiwa Bridget Mulaudzi, Maluta Steven Mufamadi, Green Synthesis in Nanomedicine and Human Health, 2021
Razia Z. Adam, Enas Ismail, Fanelwa Ajayi, Widadh Klein, Germana Lyimo, Ahmed A. Hussein
Antifungal therapy is limited to the use of azoles, echinocandins, polyenes and flucytosine (Perlin et al., 2017). The development of resistance is a consideration when treating a microbial infection. It has been found that biofilm formation on teeth and devices such as heart valves and catheters reduces the concentration of the drug by trapping it in a glucan-rich matrix polymer (Perlin et al., 2017). In yeast infections, resistance to azole antifungals has been frequently discussed and attributed to the following mechanisms: an alteration in the chemical structure of demethylase enzyme, removal of the azole from the cell by multidrug transporter pumps and compensation by other sterol synthesis enzymes in membrane biosynthesis (Lewis and Williams, 2017; Perlin et al., 2017). Echinocandins are highly effective against most Candida species, but the prevalence of C. albicans resistance has only been recorded as less than 1% (Perlin et al., 2017). However, echinocandin resistance among C. glabrata is now increasingly accompanied by azole resistance too (Pham et al., 2014). Resistance to polyenes, which include amphotericin B and nystatin, is unusual. However, reports of high minimum inhibitory concentration to amphotericin B has been found for C. albicans, C. krusei, C. rugosa, C. lusitaniae and C. glabrata (Colombo et al., 2003; Atkinson et al., 2008; Hull et al., 2012). Ultimately, there is a need for novel antifungal drugs, which address resistance, whose mechanism is more selective for fungal targets and have less host toxicity.
Candida spp.
Published in Rossana de Aguiar Cordeiro, Pocket Guide to Mycological Diagnosis, 2019
Silviane Praciano Bandeira, Glaucia Morgana de Melo Guedes, Débora de Souza Colares Maia Castelo-Branco
Polyene derivatives are also an important tool for the treatment of fungal infections. These drugs act by binding to the ergosterol of the lipid bilayer of the fungal cell membrane, disrupting the cell architecture. They lead to the formation of pores, through which ions and molecules important for the survival of the microorganism are lost, causing its death (Akins, 2005). This group includes nystatin and amphotericin B. The use of the former is limited to cutaneous or mucosal application. Amphotericin B, in turn, is often the last resource for serious fungal infections, at the expense of high nephrotoxicity to the host, leading to severe hypokalemia and renal failure. Lipid formulations, the best-tolerated drug options, still present toxicity and are costly (Vincent et al., 2013).
Therapeutic Approach in Fungal Keratitis
Published in Mahendra Rai, Marcelo Luís Occhiutto, Mycotic Keratitis, 2019
Victoria Díaz-Tome, María Teresa-Rodríguez Ares, Rubén Varela-Fernández, Rosario Touriño-Peralba, Miguel González-Barcia, Laura Martínez-Pérez, María Jesús Lamas, Francisco J. Otero-Espinar, Anxo Fernández-Ferreiro
Classical pharmacological therapy includes polyenes as the first-line drugs due to its effectiveness. Nevertheless, numerous reports of infections resistance to the first-line group and amphotericin side effects led to a new therapeutic line, including second and third generation drugs, such as triazoles, among others. Despite this, surgical treatments remain effective, although they are only used when pharmacological treatment does not respond or corneal thinning is present.
Echinocandins – structure, mechanism of action and use in antifungal therapy
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Mateusz Szymański, Sandra Chmielewska, Urszula Czyżewska, Marta Malinowska, Adam Tylicki
Until the end of the 20th century, azoles, polyenes, and flucytosine were mainly used to treat mycoses. These classes of drugs can cause serious side effects related to their hepato- and nephrotoxicity. In addition, many fungal strains have developed resistance to these antibiotics, which significantly reduces their efficacy6. In rare cases, cross-resistance to polyenes and azoles may occur, raising concerns about the future of antifungals targeting membrane ergosterol (polyens) and sterol synthesis (azoles)7. In addition, there are frequent drug-drug reactions associated with interactions of the aforementioned drugs and their metabolites in the body8. This has prompted the search for alternative agents to combat fungal infections. Echinocandins are a class of antifungal drugs that are fungicidal against many fungi including Candida species, but are fungistatic to the Aspergillus genus. This class of drugs has been found to cause milder side effects compared to polyenes and azoles9. The mechanism of action based on the inhibition of fungal-specific metabolic pathway and limited side effects have resulted in increasing interest and use of this class of drugs10.
Efficacy and safety of Isavuconazole for the treatment of invasive Aspergillus infection - an update of the literature
Published in Expert Opinion on Pharmacotherapy, 2022
Geetha Sivasubramanian, Pranatharthi H Chandrasekar
Invasive aspergillosis(IA) is a devastating infection in high-risk immunocompromised patients [1,2]. It remains a major cause of morbidity and mortality in transplant recipients and cancer patients despite the availability of effective antifungal treatment as well as]antifungal prophylaxis protocols [3–19]. In addition, there has been an emergence of IA in critically ill patients such as those with severe lung inflammation from influenza and SARS-CoV-2 infection [20–28]. Many lack classic risk factors for IA. With expanding host populations vulnerable to severe IA, there is a growing need for safe and effective anti-fungal agents. Antifungal classes currently available for treating IA include polyenes, azoles, and echinocandins [19]. There are many challenges involved in the management including toxicities, drug–drug interactions, limitations in the spectrum of antifungal activities as well as emergence of resistance [29,30]. Isavuconazole (ISZ), one of the newer triazole agents has shown good clinical efficacy against IA. This article provides an updated review of ISZ including data on its efficacy, safety and tolerability, and its role in the management of IA. As data in children is limited, this review is confined to adults patients.
In vivo antifungal activities of farnesol combined with antifungal drugs against murine oral mucosal candidiasis
Published in Biofouling, 2021
Chengxi Li, Zheng Xu, Siqi Liu, Yun Huang, Wei Duan, Xin Wei
Interactions of antifungal drugs and/or farnesol on oral candidiasis were further tested in the infected mice. In the nystatin treatment group, the doses of farnesol reported here were 25, 50, and 100 μM, because farnesol was not effective at a concentration less than 25 μM in combination with nystatin in vivo. The animals were divided into five subgroups with five mice per group: (1) control; (2) 50 μg ml−1 nystatin in a single dose; (3) 50 μg ml−1 nystatin combined with 25 μM farnesol; (4) 50 μg ml−1 nystatin combined with 50 μM farnesol; and (5) 50 μg ml−1 nystatin combined with 100 μM farnesol. Polyenes have limited utility because of their poor absorbance through the gut; therefore, topical application is the principal means of nystatin administered in oral candidiasis. The mixtures (50 μl) of nystatin and farnesol (or vehicle) were applied orally and topically on the tongue surface using a round-end needle (not via drinking water) at 3, 24, and 27 h after C. albicans inoculation.