Are In Vitro Susceptibilities to Azole Antifungals Predictive of Clinical Outcome in the Treatment of Candidemia?

Abstract

The purpose of this review is to critically analyze published data evaluating the impact of azole pharmacokinetic and pharmacodynamic parameters, MICs, and Candida species on clinical outcomes in patients with candidemia. Clinical breakpoints (CBPs) for fluconazole and voriconazole, which are used to determine susceptibility, have been defined by the Clinical and Laboratory Standards Institute (CLSI) for Candida species. Studies evaluating the relationship between treatment efficacy and in vitro susceptibility, as well as the pharmacodynamic targets, have been conducted in patients treated with fluconazole for candidemia; however, for species other than Candida albicans and Candida glabrata, and for other forms of invasive candidiasis, data remain limited and randomized trials are not available. Limited data evaluating these relationships with voriconazole are available. While pharmacodynamic targets for posaconazole and isavuconazole have been proposed based upon studies conducted in murine models, CBPs have not been established by CLSI. Fluconazole remains an important antifungal agent for the treatment of candidemia, and data supporting its use based on in vitro susceptibility are growing, particularly for C. albicans and C. glabrata Further investigation is needed to establish the roles of voriconazole, posaconazole, and isavuconazole in the treatment of candidemia and for all agents in the treatment of other forms of invasive candidiasis.

Keywords: Candida; antifungal; azole; clinical breakpoints; outcomes; pharmacodynamics; pharmacokinetics; susceptibility testing.