Optimizing the Treatment of Invasive Candidiasis—A Case for Combination Therapy
Rachel Wake, Phoebe E Allebone-Salt, Larissa L.H. John, Ben A Caswall, Nelesh P. Govender, Ronen Ben‐Ami, Lyle Murray, Clare Logan, Thomas S. Harrison, Tihana Bicanic
Abstract
Abstract Invasive candidiasis is a rising global health threat with increasing incidence, persistently high mortality, and diminishing treatment options. Antifungal resistance has rapidly emerged and spread, with multidrug-resistant species deemed an urgent and serious threat. While acknowledging the key role of antifungal stewardship and infection control in curbing spread, we examine the role of antifungal monotherapy in driving resistance and the potential for combination therapy to prevent stress adaptation and emergence of drug resistance. In addition to its role in mitigating resistance, combination treatment may improve drug penetration, expedite fungal clearance, and allow lower, less toxic doses of individual drugs to be used. A growing body of laboratory-based evidence suggests that antifungal combinations can yield synergistic activity against Candida spp., including against frequently multidrug-resistant Candida auris. It is imperative to test these combinations in clinical trials, incorporating resistance end points as a marker of success.