Cryptococcosis: update on therapeutics and new targets

Cryptococcus neoformans was recently declared a top priority fungal pathogen because of its propensity to cause a life-threatening meningoencephalitis, which continues to have high mortality and morbidity despite antifungal therapy. Our goal is to review recent developments in antifungal therapy while synthesizing how these are integrated into advances in understanding the pathophysiology of cryptococcosis.

The therapeutic outcomes for cryptococcosis continue to improve but the disease still carries an unacceptably high mortality and morbidity. Advances in therapy have largely come from optimizing the use of existing antifungal drugs, management of intracerebral and early diagnosis. A major development in the past decade was the recognition that immune responses contributed to damage in cryptococcosis, which has led to new research on the use of adjunctive immune modulators.

While progress continues to be made in the therapy of cryptococcosis by finding better ways to use existing antifungal agents and improve clinical management it is possible that this strategy is reaching its asymptote. Consequently, transformative reductions in mortality and morbidity are likely to require new antifungal agents and/or adjunctive immunotherapies. Fortunately, there are there several promising approaches in the horizon that will hopefully future drive clinical investigation.