Time to re-evaluate combination antifungal therapy for invasive aspergillosis and other invasive mycoses.

Abstract

Mortality from invasive aspergillosis remains unacceptably high, and the currently recommended treatment of triazoles is further challenged by rising resistance to these first-line agents. A previous randomised controlled trial of combination therapy with voriconazole plus anidulafungin versus voriconazole alone showed that the combination was safe and associated with a clinically significant reduction in all-cause mortality that, however, failed narrowly to meet conventional levels of significance. In this Personal View, we argue against a binary, negative interpretation of these results, and that the totality of the laboratory and clinical evidence favours a triazole-echinocandin combination for the treatment of immunocompromised patients with proven or probable invasive aspergillosis. Renewed efforts are needed to optimise and evaluate other combination approaches for aspergillosis and other life-threatening invasive fungal diseases as a means by which to mitigate antifungal resistance, maximise and prolong the utility of old and new agents, and drive down mortality.