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Keywords = opelconazole

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11 pages, 672 KiB  
Systematic Review
Recent Antifungal Pipeline Developments against Candida auris: A Systematic Review
by Rogelio de J. Treviño-Rangel, Gloria M. González, Alexandra M. Montoya, Olga C. Rojas, Mariana Elizondo-Zertuche and Neri A. Álvarez-Villalobos
J. Fungi 2022, 8(11), 1144; https://doi.org/10.3390/jof8111144 - 28 Oct 2022
Cited by 15 | Viewed by 5871
Abstract
The alarming spread and impact of multidrug-resistant Candida auris infections alongside the limited therapeutic options have prompted the development of new antifungals. These promising agents are currently in different stages of development, offering novel dosing regimens and mechanisms of action. A systematic search [...] Read more.
The alarming spread and impact of multidrug-resistant Candida auris infections alongside the limited therapeutic options have prompted the development of new antifungals. These promising agents are currently in different stages of development, offering novel dosing regimens and mechanisms of action. A systematic search in MEDLINE, EMBASE, Web of Science, and Scopus up to 27 June 2022 was conducted to find relevant articles reporting data of in vitro activity and in vivo efficacy of investigational antifungals against C. auris. These included new additions to existing antifungal classes (rezafungin and opelconazole), first-in-class drugs such as ibrexafungerp, manogepix/fosmanogepix, olorofim and tetrazoles (quilseconazole, oteseconazole and VT-1598), as well as other innovative agents like ATI-2307, MGCD290 and VL-2397. From 592 articles retrieved in the primary search, 27 met the eligibility criteria. The most studied agent was manogepix/fosmanogepix (overall MIC90: 0.03 mg/L), followed by ibrexafungerp (overall MIC90: 1 mg/L) and rezafungin (overall MIC mode: 0.25 mg/L), while VT-1598 and ATI-2307 were the least explored drugs against C. auris. All these compounds demonstrated significant improvements in survival and reduction in tissue fungal burden on neutropenic animal models of candidemia due to C. auris. Continual efforts towards the discovery of new treatments against this multidrug-resistant fungus are essential. Full article
(This article belongs to the Special Issue Antifungal Drug Discovery: Novel Therapies and Approaches)
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20 pages, 917 KiB  
Review
Pharmacodynamics, Mechanisms of Action and Resistance, and Spectrum of Activity of New Antifungal Agents
by Nathan P. Wiederhold
J. Fungi 2022, 8(8), 857; https://doi.org/10.3390/jof8080857 - 16 Aug 2022
Cited by 42 | Viewed by 9490
Abstract
Several new antifungals are currently in late-stage development, including those with novel pharmacodynamics/mechanisms of action that represent new antifungal classes (manogepix, olorofim, ATI-2307, GR-2397). Others include new agents within established classes or with mechanisms of action similar to clinically available antifungals (ibrexafungerp, rezafungin, [...] Read more.
Several new antifungals are currently in late-stage development, including those with novel pharmacodynamics/mechanisms of action that represent new antifungal classes (manogepix, olorofim, ATI-2307, GR-2397). Others include new agents within established classes or with mechanisms of action similar to clinically available antifungals (ibrexafungerp, rezafungin, oteseconazole, opelconazole, MAT2203) that have been modified in order to improve certain characteristics, including enhanced pharmacokinetics and greater specificity for fungal targets. Many of the antifungals under development also have activity against Candida and Aspergillus strains that have reduced susceptibility or acquired resistance to azoles and echinocandins, whereas others demonstrate activity against species that are intrinsically resistant to most clinically available antifungals. The tolerability and drug–drug interaction profiles of these new agents also appear to be promising, although the number of human subjects that have been exposed to many of these agents remains relatively small. Overall, these agents have the potential for expanding our antifungal armamentarium and improving clinical outcomes in patients with invasive mycoses. Full article
(This article belongs to the Special Issue Pharmacodynamics of Antifungal Drugs)
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