Abstract
Current treatment for invasive fungal diseases is limited to three classes of antifungal drugs: azoles, polyenes, and echinocandins. The most recently introduced antifungal class, the echinocandins, was first approved nearly 30 years ago. The limited antifungal drug portfolio is rapidly losing its clinical utility due to the inexorable rise in the incidence of invasive fungal infections and the emergence of multidrug resistant (MDR) fungal pathogens. New antifungal therapeutic agents and novel approaches are desperately needed. Here, we detail attempts to exploit the antifungal and immunoregulatory properties of host defense peptides (HDPs) in the design and evaluation of new antifungal therapeutics and discuss historical limitations and recent advances in this quest.
Highlights
Invasive fungal infections are a global health concern, with high rates of incidence and mortality, in immunocompromised patients [1,2,3]
Numerous clinical isolates have emerged that are resistant to all three classes of approved antifungals [4,9,10,11,12,13], highlighted by the international spread of multidrug resistant (MDR) C. auris, which is classified by CDC as a serious threat [14,15]
Despite the challenges of antifungal drug development in general, and the inherent barriers encountered in developing peptide drugs, there is reason to be hopeful that the biological properties of host defense peptides (HDPs) may contribute to the quest for new antifungal agents
Summary
Invasive fungal infections are a global health concern, with high rates of incidence and mortality, in immunocompromised patients [1,2,3]. An estimated 200,000 cases of Aspergillus spp. infections occur annually with invasive disease primarily affecting immunocompromised patients. Invasive aspergillosis causes death in up to 50% of affected patients, whereas left untreated, as often occurs in developing countries, lethality approaches 100% [1]. Cryptococcosis is initially a pulmonary infection, in the immunosuppressed patient the organism commonly disseminates systemically to the central nervous system (CNS) causing meningoencephalitis with an estimated 70% mortality [1]. There are three classes of antifungals: azoles, polyenes, and echinocandins (Table 2). Azoles are the most widely used class of antifungal agents because of their bioavailability as oral and intravenous (i.v.) formulations and their excellent safety profiles. Cryptococcus spp. and endemic mycoses [7]
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