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      CD101: a novel long‐acting echinocandin

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          Summary

          CD101 is a novel echinocandin drug being developed to treat severe fungal infections including invasive candidiasis. We have performed a series of studies to evaluate the antifungal properties of CD101 against both echinocandin‐susceptible and ‐resistant Candida strains. Antifungal susceptibility testing performed on a collection of 95 Candida strains including 30 caspofungin‐resistant isolates containing fks mutations demonstrated comparable antifungal potency of CD101 relative to micafungin (MCF) across different Candida species. Comparable kinetic inhibition of glucan synthase activity was also observed for CD101 and MCF on both wild‐type (WT) and resistant fks mutant Candida strains. Similarly, both drugs yielded nearly identical values for a mutant prevention concentration. In a murine model of invasive candidiasis, CD101 displayed better or at least comparable efficacy relative to MCF in treating WT or fks mutant Candida albicans. An exceptional long‐lived pharmacokinetic profile was observed in mice following a single dose of CD101. Collectively, CD101 has great potential not only in treating invasive Candida infections but also in preventing emergence of resistance to currently approved echinocandin drugs.

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          Executive Summary: Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America.

          It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.
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            Echinocandin antifungal drugs.

            The echinocandins are large lipopeptide molecules that are inhibitors of beta-(1,3)-glucan synthesis, an action that damages fungal cell walls. In vitro and in vivo, the echinocandins are rapidly fungicidal against most Candida spp and fungistatic against Aspergillus spp. They are not active at clinically relevant concentrations against Zygomycetes, Cryptococcus neoformans, or Fusarium spp. No drug target is present in mammalian cells. The first of the class to be licensed was caspofungin, for refractory invasive aspergillosis (about 40% response rate) and the second was micafungin. Adverse events are generally mild, including (for caspofungin) local phlebitis, fever, abnormal liver function tests, and mild haemolysis. Poor absorption after oral administration limits use to the intravenous route. Dosing is once daily and drug interactions are few. The echinocandins are widely distributed in the body, and are metabolised by the liver. Results of studies of caspofungin in candidaemia and invasive candidiasis suggest equivalent efficacy to amphotericin B, with substantially fewer toxic effects. Absence of antagonism in combination with other antifungal drugs suggests that combination antifungal therapy could become a general feature of the echinocandins, particularly for invasive aspergillosis.
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              Echinocandin resistance: an emerging clinical problem?

              Echinocandin resistance in Candida is a great concern, as the echinocandin drugs are recommended as first-line therapy for patients with invasive candidiasis. Here, we review recent advances in our understanding of the epidemiology, underlying mechanisms, methods for detection and clinical implications.
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                Author and article information

                Journal
                Cell Microbiol
                Cell. Microbiol
                10.1111/(ISSN)1462-5822
                CMI
                Cellular Microbiology
                John Wiley and Sons Inc. (Hoboken )
                1462-5814
                1462-5822
                22 July 2016
                September 2016
                : 18
                : 9 , Fungal Cell Wall ( doiID: 10.1111/cmi.v18.9 )
                : 1308-1316
                Affiliations
                [ 1 ] Public Health Research Institute, Rutgers Biomedical and Health SciencesNew Jersey Medical School Newark NJUSA
                [ 2 ]Cidara Therapeutics, Inc. San Diego CAUSA
                Author notes
                [*] [* ]For correspondence. E‐mail perlinds@ 123456njms.rutgers.edu ; Tel. (+00) 973 854‐3200; Fax (+00) 973 854‐3101.
                Article
                CMI12640 CMI-16-0084.R2
                10.1111/cmi.12640
                5096055
                27354115
                0e24cf52-45f3-4e65-aca7-8d4122e77477
                © 2016 The Authors Cellular Microbiology Published by John Wiley & Sons Ltd

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 01 March 2016
                : 22 June 2016
                : 25 June 2016
                Page count
                Pages: 9
                Funding
                Funded by: Cidara Therapeutic, Inc.
                Categories
                Special Issue ‐ Original article
                Special Issue ‐ Original articles
                Custom metadata
                2.0
                cmi12640
                cmi12640-hdr-0001
                September 2016
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.9.6 mode:remove_FC converted:04.11.2016

                Microbiology & Virology
                Microbiology & Virology

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