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The treatment of invasive fungal infections remains challenging due to limitations in currently available antifungal therapies including toxicity, interactions, restricted routes of administration, and drug resistance. This review focuses on novel therapies in clinical development, including drugs and a device. These drugs have novel mechanisms of action to overcome resistance, and some offer new formulations providing distinct advantages over current therapies to improve safety profiles and...
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BACKGROUND: Itraconazole is the preferred azole for histoplasmosis in the current Infectious Diseases Society of America guidelines. Voriconazole is increasingly used as treatment for histoplasmosis; it has in-vitro activity against Histoplasma capsulatum and has shown success in case reports and small case series but may have a lower barrier to resistance. No comparative studies have been published. METHODS: We constructed a single-center retrospective cohort of adult patients diagnosed...
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The dimorphic mycoses (DM) of the United States, Histoplasma, Coccidioides, and Blastomyces, commonly known as endemic mycoses of North America (in addition to Paracoccidioides), are increasingly being diagnosed outside their historical areas of endemicity. Despite this trend, the maps outlining their geographical distributions have not been updated in more than half a century using a large, nationwide database containing individual patient-level data.Retrospective analysis of >45 million...
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The epidemiology of invasive fungal infections is changing, with new populations at risk and the emergence of resistance caused by the selective pressure from increased usage of antifungal agents in prophylaxis, empiric therapy, and agriculture. Limited antifungal therapeutic options are further challenged by drug–drug interactions, toxicity, and constraints in administration routes. Despite the need for more antifungal drug options, no new classes of antifungal drugs have become available...
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Abstract Coronavirus disease 2019 (COVID-19) can become complicated by secondary invasive fungal infections (IFIs), stemming primarily from severe lung damage and immunologic deficits associated with the virus or immunomodulatory therapy. Other risk factors include poorly controlled diabetes, structural lung disease and/or other comorbidities, and fungal colonization. Opportunistic IFI following severe respiratory viral illness has been increasingly recognized, most notably with...
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Abstract Invasive fungal infections continue to increase as at-risk populations expand. The high associated morbidity and mortality with fungal diseases mandates the continued investigation of novel antifungal agents and diagnostic strategies that include surrogate biomarkers. Biologic markers of disease are useful prognostic indicators during clinical care, and their use in place of traditional survival endpoints may allow for more rapid conduct of clinical trials requiring...
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As the first part of an update to the clinical practice guideline on the management of histoplasmosis in adults, children, and pregnant people, developed by the Infectious Diseases Society of America, we present 4 updated recommendations. These recommendations span treatment of asymptomatic Histoplasma pulmonary nodules (histoplasmomas), mild acute pulmonary histoplasmosis, and moderate acute pulmonary histoplasmosis. The panel's recommendations are based on evidence derived from systematic...
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Histoplasmosis is a major AIDS-defining illness in Latin America. Liposomal amphotericin B (L-AmB) is the drug of choice for treatment, but access is restricted due to the high drug and hospitalization costs of the conventional long regimens.Prospective randomized multicenter open-label trial of one or two-dose induction therapy with L-AmB versus control for disseminated histoplasmosis in AIDS, followed by oral itraconazole therapy. We randomized subjects to: (i) Single dose 10 mg/kg of...
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Objectives: To evaluate the safety and efficacy of two dosing regimens of oral ibrexafungerp (formerly SCY078), a novel orally bioavailable b-glucan synthase inhibitor, in subjects with invasive candidiasis versus the standard of care (SOC) and to identify the dose to achieve target exposure (15.4 lMÁh) in .80% of the intended population. Methods: In a multinational, open-label study, patients with documented invasive candidiasis were randomized to receive step-down therapy to one of three...
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