Abstract
Candida albicans represents the most frequent isolated yeast from bloodstream infections. Despite the remarkable progress in diagnostic and therapeutic approaches, these infections continue to be a critical challenge in intensive care units worldwide. The economic cost of bloodstream fungal infections and its associated mortality, especially in debilitated patients, remains unacceptably high. Candida albicans is a highly adaptable microorganism, being able to develop resistance following prolonged exposure to antifungals. Formation of biofilms, which diminish the accessibility of the antifungal, selection of spontaneous mutations that increase expression or decreased susceptibility of the target, altered chromosome abnormalities, overexpression of multidrug efflux pumps and the ability to escape host immune defenses are some of the factors that can contribute to antifungal tolerance and resistance. The knowledge of the antifungal resistance mechanisms can allow the design of alternative therapeutically options in order to modulate or revert the resistance. We have focused this review on the main factors that are involved in antifungal resistance and tolerance in patients with C. albicans bloodstream infections.
Highlights
Candida albicans coexists in humans as commensal without damage to the host, colonizing several body locations like the skin, genital tract, and gastro-intestinal tract [1]
One of the main factors that contribute to the high mortality rate associated with Candidaemia is the difficulty in diagnosis, due to the nonspecific clinical symptoms of systemic fungal infection and delayed laboratorial detection methods, as well as the subsequent delay in initiation of adequate antifungal therapy [12,13]
Since most filamentous fungi lack cytosine deaminase, the spectrum of flucytosine is restricted to pathogenic yeasts. 5-Flucytosine should be used in combination with other antifungal agents namely amphotericin B, rather than in monotherapy, because resistance develops at high frequency [24]
Summary
Candida albicans coexists in humans as commensal without damage to the host, colonizing several body locations like the skin, genital tract, and gastro-intestinal tract [1]. In parallel to the advance of medical procedures, the incidence of bloodstream Candida infections increased as well as the associated mortality rate, being C. albicans the most frequent yeast isolated from patient biological samples [4,5,6,7,8,9]. Colonization of the skin and mucous membranes and the alteration or disruption of natural host barriers, like wounds, surgery, and the insertion of indwelling intravascular catheters are the main predisposing factors for Candida infections [6,10,11]. One of the main factors that contribute to the high mortality rate associated with Candidaemia is the difficulty in diagnosis, due to the nonspecific clinical symptoms of systemic fungal infection and delayed laboratorial detection methods, as well as the subsequent delay in initiation of adequate antifungal therapy [12,13]. This review highlights the multiple attributes of C. albicans that may influence and promote antifungal resistance and tolerance
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