Review of the Current Management of Urinary Tract Infections due to Fluconazole-Resistant and Non-Albicans Candida Species

Abstract

The management of fungal infections is challenging, especially given the continued increase in fluconazole resistance and prevalence of non-albicans Candida spp. Urinary tract infections due to non-albicans and fluconazole-resistant Candida are particularly problematic given the uncertainty in determining true infection from colonization and the limited number of antifungal agents with adequate penetration to the site of infection. While our understanding of mechanisms of resistance and pharmacokinetics and pharmacodynamics continues to improve, it is combatted by the emergence of novel, difficult-to-manage pathogens such as C. auris. The purpose of this review is to summarize recent data regarding the management of urinary tract infections due to non-albicans and fluconazole-resistant Candida spp. with a focus on mechanisms of resistance, pharmacokinetics and pharmacodynamics, and treatment strategies. Advances in molecular techniques have improved our understanding of the mechanisms responsible for antifungal resistance, especially to the echinocandins and azole antifungal classes. Additionally, increased knowledge of the pharmacokinetic and pharmacodynamic properties that govern available antifungal agents has enhanced the ability to optimize dosing, especially for extravascular fungal infections. Unfortunately, these developments in the pre-clinical arena have not been matched by additional high-quality clinical data, and therefore, the optimal management strategies for fungal UTIs remain elusive. The lack of adequate new clinical data to guide optimal management of UTIs due to fluconazole-resistant and non-albicans Candida, combined with the dearth of novel antifungal agents, leaves fluconazole, amphotericin B deoxycholate, and flucytosine as the drugs of choice for these infections. Further data regarding urinary concentrations and optimal urinary PK/PD parameters may allow for the use of other agents, such as the echinocandins, in certain situations. Several novel antifungal agents are currently in clinical development with adequate in vitro activity against fluconazole-resistant and non-albicans Candida, although their utility in the treatment of UTIs requires further investigation.