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      Salvage Treatment for Invasive Aspergillosis and Mucormycosis: Challenges, Recommendations and Future Considerations

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          Abstract

          Invasive mold diseases are devastating systemic infections which demand meticulous care in selection, dosing, and therapy monitoring of antifungal drugs. Various circumstances regarding PK/PD properties of the applied drug, resistance/tolerance of the causative pathogen or host intolerability can lead to failure of the initial antifungal therapy. This necessitates treatment adaption in the sense of switching antifungal drug class or potentially adding another drug for a combination therapy approach. In the current state of drastically limited options of antifungal drug classes adaption of therapy remains challenging. Current guidelines provide restricted recommendations only and emphasize individual approaches. However, novel antifungals, incorporating innovative mechanisms of action, show promising results in late stage clinical development. These will expand options for salvage therapy in the future potentially as monotherapy or in combination with conventional or other novel antifungals. We outline current recommendations for salvage therapy including PK/PD considerations as well as elucidate possible future treatment options for invasive aspergillosis and mucormycosis.

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          Most cited references104

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          Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium

          Mucormycosis is a difficult to diagnose rare disease with high morbidity and mortality. Diagnosis is often delayed, and disease tends to progress rapidly. Urgent surgical and medical intervention is lifesaving. Guidance on the complex multidisciplinary management has potential to improve prognosis, but approaches differ between health-care settings. From January, 2018, authors from 33 countries in all United Nations regions analysed the published evidence on mucormycosis management and provided consensus recommendations addressing differences between the regions of the world as part of the "One World One Guideline" initiative of the European Confederation of Medical Mycology (ECMM). Diagnostic management does not differ greatly between world regions. Upon suspicion of mucormycosis appropriate imaging is strongly recommended to document extent of disease and is followed by strongly recommended surgical intervention. First-line treatment with high-dose liposomal amphotericin B is strongly recommended, while intravenous isavuconazole and intravenous or delayed release tablet posaconazole are recommended with moderate strength. Both triazoles are strongly recommended salvage treatments. Amphotericin B deoxycholate is recommended against, because of substantial toxicity, but may be the only option in resource limited settings. Management of mucormycosis depends on recognising disease patterns and on early diagnosis. Limited availability of contemporary treatments burdens patients in low and middle income settings. Areas of uncertainty were identified and future research directions specified.
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            Practice Guidelines for the Diagnosis and Management of Aspergillosis: 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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              Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline

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                Author and article information

                Journal
                Infect Drug Resist
                Infect Drug Resist
                idr
                Infection and Drug Resistance
                Dove
                1178-6973
                12 April 2023
                2023
                : 16
                : 2167-2178
                Affiliations
                [1 ]Division of Infectious Diseases, Department of Internal Medicine, Medical University of Graz , Graz, Austria
                [2 ]Biotechmed-Graz , Graz, Austria
                [3 ]Clinical Pharmacokinetics Unit, Division of Intensive Care and Emergency Medicine, Department of Internal Medicine I, Medical University of Innsbruck , Innsbruck, Austria
                [4 ]Department of Microbiology, Faculty of Pharmacy and Biochemistry, University of Zagreb , Zagreb, Croatia
                [5 ]Clinical and Translational Fungal-Working Group, University of California San Diego , San Diego, CA, USA
                [6 ]Translational Medical Mycology Research Unit, ECMM Excellence Center for Medical Mycology, Medical University of Graz , Graz, Austria
                Author notes
                Correspondence: Martin Hoenigl, Division of Infectious Diseases, Department of Internal Medicine, Medical University of Graz , Auenbruggerplatz 15, Graz, 8036, Austria, Tel +43 31638531425, Email hoeniglmartin@gmail.com
                Author information
                http://orcid.org/0000-0002-7795-4406
                http://orcid.org/0000-0003-2861-3258
                http://orcid.org/0000-0001-6656-3648
                http://orcid.org/0000-0001-8783-1306
                http://orcid.org/0000-0001-7049-960X
                http://orcid.org/0000-0002-1653-2824
                Article
                372546
                10.2147/IDR.S372546
                10106327
                37077251
                0268c86c-230b-4a5a-98e3-36324afbac82
                © 2023 Egger et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 18 December 2022
                : 23 March 2023
                Page count
                Figures: 1, Tables: 2, References: 107, Pages: 12
                Categories
                Review

                Infectious disease & Microbiology
                invasive fungal infections,aspergillosis,mucormycosis,salvage therapy

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