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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).
Diagnosis and Treatment of Fungal Keratitis
Published in Mahendra Rai, Marcelo Luís Occhiutto, Mycotic Keratitis, 2019
Eye drops of 5% natamycin, a polyene macrolide antifungal agent, can inhibit both the growth of various molds and yeasts and the production of mycotoxins. The polyene macrolide ring on the molecular structure reacts with the cell wall of fungi (molds and yeasts) or ergosterol on the plasma membrane, causing rupture of the cell wall and plasma membrane, leakage of the cell fluid and cytoplasm, and eventually death. Despite the favorable effects on FK, it has not been widely used in China due to the high price of imported products. Domestically manufactured natamycin eye drops have just entered the market with a relatively low price. In short, there are few varieties of antifungal eye drops in China, which is contrasted with the increasing incidence of FK.
Lipids of Dermatophytes
Published in Rajendra Prasad, Mahmoud A. Ghannoum, Lipids of Pathogenic Fungi, 2017
The most effective antibiotics widely used in the treatment of fungal infections are polyenes. The target of these drugs is the plasma membrane and their selectivity is based upon the difference in sterol composition of the fungus and mammalian cells. It has been postulated that the strong affinity of the hydrophilic portion of the polyene for ergosterol via hydrogen bonds allows the drug to penetrate the membrane with the hydrophobic portion sitting beside the sterol ring.90,91 These antibiotics are highly effective in the treatment of systemic mycoses but are ineffective in superficial and cutaneous mycoses caused by dermatophytes. Capek and Simek92 observed that the loss of sensitivity towards polyenes in M. gypseum and T. mentagrophytes was associated with decreased sterol content. In E. floccosum, in the presence of nystatin, irrespective of the sterol content, uptake of amino acid was decreased (Table 5), which indicates that lipids other than sterols influence the overall sensitivity of the E. floccosum membrane towards the polyenes (Sanadi and Khuller, unpublished observations).
Potential lipid-based strategies of amphotericin B designed for oral administration in clinical application
Published in Drug Delivery, 2023
Xiaoming Zhong, Jianqiong Yang, Hongyan Liu, Zhiwen Yang, Ping Luo
Molecular behavior of AmB poses a great challenge to develop an oral formulation. Due to the presence of zwitterionic nature, structural asymmetry, and amphiphilicity, AmB shows poor aqueous solubility (<1 mg/L) at the physiological pH, which can cause a significant precipitation in the gastrointestinal tract (Shim et al., 2011). Also, the drug with the polyene chain shows highly unstable at acidic or alkaline pH, leading to an easily degradation under the acidic environment in the stomach upon oral administration (Liu et al., 2017). Additionally, AmB has a poor permeability in the intestinal tract due to the high molecular weight, low solubility, and preferential interaction with the cellular membrane. The oral bioavailability of AmB exhibits a very poor data, ranging from 0.2 to 0.9% (Liu et al., 2017; Volmer et al., 2010).
An evaluation of ibrexafungerp for the treatment of invasive candidiasis: the evidence to date
Published in Expert Opinion on Pharmacotherapy, 2021
Rhonda E Colombo, Jose A Vazquez
Invasive candidiasis is a significant cause of infection-related morbidity and mortality. The increasing rate of nosocomial candidemia represents a major threat, particularly due to the emergence of multidrug-resistant Candida species, such as C. glabrata and C. auris. There are currently a limited number of antifungal options for the treatment of invasive candidiasis, and each agent has certain limitations. Unfortunately, echinocandins, the preferred initial therapy for candidemia and invasive candidiasis, are only available in intravenous formulations. Azoles, a mainstay of candidal treatment, are plagued by increasing resistance concerns and potential drug–drug interactions. Polyenes are hampered by drug-associated toxicities, as well as the need for intravenous administration. Thus, there remains a need for an additional potent antifungal agent with activity against resistant fungal pathogens, has a good bioavailability profile, is safe and easy to use, and finally, is effective in the treatment of candidemia and invasive candidiasis.
Sustained intrathecal delivery of amphotericin B using an injectable and biodegradable thermogel
Published in Drug Delivery, 2021
Wenting Lin, Tao Xu, Zhongzhi Wang, Jianghan Chen
AMB, a member of polyenes, is the first-recommended drug for the treatment of CM (Williamson et al., 2017). The pharmacokinetics studies have shown its poor penetration into the cerebrospinal fluid (CSF) and brain parenchyma due to its molecule properties (Hamill, 2013) and blood-brain barrier (BBB). BBB is an impermeable cellular interface that separates the blood from the brain, selectively allows only a few substances to pass. The concentration of AMB in CSF was approximately 0.05 mg/L following its intravenous injection, 10 times lower than used for antifungal activity (Nau et al., 2020). Besides, its intravenous administration has many side effects such as headache, fever, damage of liver and kidney, and vasculitis, etc (Nau et al., 2020)., which makes it far from being the best choice.