The Impact of Antifungal Drug Resistance in the Clinic

Abstract

This chapter critically evaluates some common assumptions regarding antifungal resistance and highlights key clinical problems that arise when managing patients with invasive infections caused by antifungal-resistant Candida species. Although this paper gives perhaps the first example of in vivo-acquired mutations in a fungal gene with a positive impact on in vivo fitness, all of the clinical isolates used in the study were acquired from semi-invasive infections of the oropharynx rather than the bloodstream of patients. The majority of patients with invasive mycoses probably fail therapy because of underlying host factors, rather than acquired resistance to the drug. One of the most underappreciated causes of treatment failures in Candida species is biofilm-mediated resistance. Problems associated with timely diagnosis and early detection of antifungal resistance in Candida species have not improved over the last two decades, as current testing approaches still rely primarily on blood cultures, which may be negative for up to 50% of patients. It is critical that the diagnostics and treatment tools to manage antifungal resistance in Candida species be developed now, along with clinical stewardship programs to effectively integrate their use in clinic, so that we are better equipped to deal with the challenges on the horizon that will be encountered in an increasingly complex and aged population of patients in the health care system.