Treatment strategies for cryptococcal infection: challenges, advances and future outlook
| Autor: | Kali R. Iyer, Leah E. Cowen, Nicole M. Revie, Nicole Robbins, Ci Fu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Antifungal Agents Combination therapy Virulence Factors Cryptococcus Antifungal drug Drug resistance Disease Review Article Microbiology 03 medical and health sciences Echinocandins Fungal Capsules Cell Wall Drug Resistance Fungal medicine Intensive care medicine Cryptococcus gattii Cryptococcus neoformans 0303 health sciences General Immunology and Microbiology biology 030306 microbiology Fungal Polysaccharides Cryptococcosis biology.organism_classification medicine.disease Infectious Diseases Fungal pathogenesis |
| Zdroj: | Nature Reviews. Microbiology |
| ISSN: | 1740-1534 |
| Popis: | Cryptococcus spp., in particular Cryptococcus neoformans and Cryptococcus gattii, have an enormous impact on human health worldwide. The global burden of cryptococcal meningitis is almost a quarter of a million cases and 181,000 deaths annually, with mortality rates of 100% if infections remain untreated. Despite these alarming statistics, treatment options for cryptococcosis remain limited, with only three major classes of drugs approved for clinical use. Exacerbating the public health burden is the fact that the only new class of antifungal drugs developed in decades, the echinocandins, displays negligible antifungal activity against Cryptococcus spp., and the efficacy of the remaining therapeutics is hampered by host toxicity and pathogen resistance. Here, we describe the current arsenal of antifungal agents and the treatment strategies employed to manage cryptococcal disease. We further elaborate on the recent advances in our understanding of the intrinsic and adaptive resistance mechanisms that are utilized by Cryptococcus spp. to evade therapeutic treatments. Finally, we review potential therapeutic strategies, including combination therapy, the targeting of virulence traits, impairing stress response pathways and modulating host immunity, to effectively treat infections caused by Cryptococcus spp. Overall, understanding of the mechanisms that regulate anti-cryptococcal drug resistance, coupled with advances in genomics technologies and high-throughput screening methodologies, will catalyse innovation and accelerate antifungal drug discovery. Cryptococcosis is a serious fungal infection for which treatment options are limited. In this Review, Cowen and colleagues discuss the current antifungal treatments available for cryptococcal infections, the challenges in developing new treatments, and ongoing efforts to identify novel therapies. |
| Databáze: | OpenAIRE |
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