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Basic Principles of Antifungal Treatment
Published in Firza Alexander Gronthoud, Practical Clinical Microbiology and Infectious Diseases, 2020
Monitor signs of drug toxicity All antifungal drugs can cause hepatotoxicity, lowest risk seen with echinocandins.Azoles: Prolonged QT interval. Visual disturbances and encephalopathy can be seen with voriconazole. IV voriconazole can result in renal toxicity.Echinocandins: Low toxicity profile. Infusion-related reaction is a rare side effect.Amphotericin B: Infusion-related reaction (lower with liposomal amphotericin B), renal toxicity, hypokalaemia, hepatotoxicity.
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
The most recently described class of antifungal drugs is the echinocandins. These drugs act quite peculiarly by preventing the synthesis of glucans in the fungal cell wall by inhibiting the enzyme 1,3-β-glucan synthase. This unique mechanism significantly reduces the occurrence of side effects, since it targets a structure that does not exist in the host cells. This class includes the drugs caspofungin, micafungin, and anidulafungin. They are expensive, but are a good therapeutic options in cases of Candida fungemia (Akins, 2005; Pfaller et al., 2012).
Micafungin
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Nicholas D. Beyda, Russell E. Lewis, Dimitrios P. Kontoyiannis
Headache and dizziness are the most commonly reported central nervous system effects reported with the echinocandins, observed in up to 12% of patients. Seizures, psychiatric disturbances, malaise, and paresthesias of hands and feet are uncommon (Cancidas, 2008; Eraxis, 2008; Mycamine, 2013). Posterior reversible encephalopathy has been reported in patients receiving micafungin, but causality is unproven.
The antifungal pipeline for invasive fungal diseases: what does the future hold?
Published in Expert Review of Anti-infective Therapy, 2023
Chin Fen Neoh, Wirawan Jeong, David CM Kong, Monica A Slavin
Ibrexafungerp, a semisynthetic derivative of enfumafungin, is the first-in-class triterpenoid. It has similar mechanism of action as echinocandins, namely, inhibiting β-(1,3)-D-glucan synthesis that is an essential cell wall component of fungi. Ibrexafungerp is available in oral formulation with a bioavailability of 35% to>51%; enhanced absorption is noted with food or in an acidic environment [33] (Table 1). Hence, ibrexafungerp could be an attractive alternative following IV echinocandins, benefiting patients who can be discharged early from hospital or require prolonged courses of antifungal treatment at the outpatient setting (e.g. those with bone and joint infections). Liposomal IV formulation of ibrexafungerp is currently under investigation, with phase I trial completed in 2021. Ibrexafungerp has excellent distribution to most tissues including kidney, lung, liver, spleen, vaginal tissue, bone marrow, skin and skeletal muscle (except for CNS) [34]. Ibrexafungerp is primarily eliminated via bile and feces (~90%), with little excreted in urine (~1.5%) [34]. Therefore, it may have limited role for CNS or urinary tract infections. Though ibrexafungerp inhibits CYP2C8, CYP3A4, and p-glycoprotein (P-gp), studies have suggested that these interactions were not clinically significant and therefore, ibrexafungerp has a relatively lower risk of drug-drug interactions [35,36], an advantage over triazoles. Dosage adjustment of ibrexafungerp, however, is required with concomitant use of a strong CYP3A4 inhibitor [37].
Evolution of antifungals for invasive mold infections in immunocompromised hosts, then and now
Published in Expert Review of Anti-infective Therapy, 2023
Zoe Freeman Weiss, Jessica Little, Sarah Hammond
In the early 2000s, intravenous echinocandins were granted FDA approval, primarily for treatment of invasive candidiasis, and to a lesser extent, salvage therapy for invasive aspergillosis. Drugs in this class include caspofungin, micafungin, and anidulafungin. Echinocandins are semisynthetic lipopeptide antifungals that inhibit the synthesis of (1→3)-B-D-glucan, a polysaccharide of the fungal cell wall [10]. These agents have significant activity against yeast pathogens such as Candida, modest activity against mold such as Aspergillus sp. but no significant activity against the dimorphic fungi, Cryptococcus, or mucormycetes. Echinocandins are extremely well tolerated, safe, and have virtually no significant drug interactions [11]. Echinocandins are highly protein bound and penetrate into nearly every organ, though concentrations are low in the eye, uninfected spinal fluid, and urine. Daily intravenous administration hinders their current use in the outpatient setting [12].
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.