Candida albicans Antifungal Resistance and Tolerance in Bloodstream Infections: The Triad Yeast-Host-Antifungal

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.

Triazole Evolution of Candida parapsilosis Results in Cross-Resistance to Other Antifungal Drugs, Influences Stress Responses, and Alters Virulence in an Antifungal Drug-Dependent Manner

“…Our results, together with the findings in the literature, highlight the necessity of deeper investigations of antifungal resistance development in C. parapsilosis and other species, as the outcome of different antifungal treatments may depend not only on the effectiveness of administered antifungal drugs but also on the virulence cost effect that could be impacted by resistance mechanisms (36).…”

The Quiet and Underappreciated Rise of Drug-Resistant Invasive Fungal Pathogens

“…glabrata , which can cause intraabdominal candidiasis, show a pronounced immune evasion and reduced neutrophil influx, resulting in progression from peritonitis to abscesses [ 67 ]. Consequently, as discussed above, various factors associated with the host, pathogen, and antifungal drugs together facilitate the emergence of antifungal resistance [ 70 ]. Delivering drugs at an appropriate level at the site of infection is critical to achieve pharmacodynamic targets attainment to maximize clinical outcome.…”

Antimicrobial peptide AMP-17 exerts anti-Candida albicans effects through ROS-mediated apoptosis and necrosis

“…Although signi cant progress has been made in diagnosis and treatment, these infections continue to be a serious challenge for ICUs (intensive care units) worldwide. The yeast state of C. albicans with unique structure and characteristics is more likely to spread in the blood circulation of debilitated patients [7,20]. Based on this diffusion property, inhibition of the proliferation of C. albicans yeast is an effective antifungal method.…”

“…Such patients with speci c risk factors are generally susceptible to C. albicans, and the site of infection may be almost all organs [5]. In recent years, due to the widespread use of traditional antifungal agents such as triazoles, the isolation rate of resistant C. albicans strains has been increasing, which has brought great challenges to the treatment of C. albicans infection [6][7]. In this context, there is a critical need to develop effective antifungal agents with unique structures and mechanism of action to treat infections caused by Candida species.…”