Responding to the Emergence of Antifungal Drug Resistance: Perspectives from the Bench and the Bedside

Abstract

The incidence of serious fungal infections is increasing rapidly, and yet the rate of new drugs becoming available to treat them is slow. The limited therapeutic armamentarium is a challenge for clinicians, because the available drugs are often toxic, expensive, difficult to administer, ineffective or a combination of all four. Given this setting, the emergence of resistance is especially concerning, and a review of the topic is timely. Here we discuss antifungal drug resistance in Candida spp. and Aspergillus spp. with reference to the most commonly used first-line antifungal agents – azoles and echinocandins. We review the resistance mechanisms of the leading pathogens, how resistance can be identified in the diagnostic lab and the clinical implications of resistance once detected.

Alkylimidazolium Ionic Liquids as Antifungal Alternatives: Antibiofilm Activity Against Candida albicans and Underlying Mechanism of Action

“…annually around the globe (Fuentefria et al, 2018;Almeida et al, 2019). Treatment of fungal infections is a challenge in clinical settings because of limited number of antifungal drugs for treating invasive infections, inefficacy in preventing infections, difficulty in administering and combination of all these factors (Desai et al, 2014;Beardsley et al, 2018). This is amplified by emerging antifungal resistance and resistance conferred by fungal biofilms.…”

“…Effective ionic liquids are suitable for prospective applications in antifungal creams for topical applications, disinfection of surgical tools and treatment of dental lines in hospital settings. The results of in vitro assays are useful for guiding treatment choices (Beardsley et al, 2018) and complementation with in vivo studies is necessary for considering potential clinical applications. Schrekker et al (2016) evaluated the biocompatibility of imidazolium ionic liquids in vitro using L929 fibroblast cells of mice.…”

Rapid and Low-Cost Culture-Based Method for Diagnosis of Mucormycosis Using a Mouse Model

“…cultures and fungal identification, even at the genus level only, allow for the appropriate choice of antifungal regimens and further assessment of antifungal resistance patterns and emerging resistance Beardsley et al, 2018). Although some molecular identification methods may be able to provide results within a few hours, the microculture assay described in this study does not require specialized training or equipment.…”

Immunotherapy against Systemic Fungal Infections Based on Monoclonal Antibodies

“…Candida albicans is an extremely adaptable pathogen and dangerous for human health since it can resist adverse conditions in different in vivo conditions, including nutrient availability, temperature variation, osmolarity, pH and oxygen availability [18]. Moreover, it can also resist against antifungals and form mixed biofilms with other species [173,174].…”