Antifungal Susceptibility and Resistance-Associated Gene Expression in Nosocomial Candida Isolates

Background: Nosocomial infections represent a significant clinical burden due to high morbidity, mortality and healthcare costs. Invasive fungal infections, particularly those caused by Candida species, are of growing concern due to increasing antifungal resistance, which limits therapeutic options and worsens patient outcomes. This study aimed to characterize the prevalence, species distribution, antifungal susceptibility profiles, and molecular mechanisms of resistance in clinical Candida isolates from hospitalized patients. Methods: A cross-sectional study was conducted involving 55 hospitalized patients, yielding 60 isolates from blood, secretions, fluids, and catheter tips. Species identification was performed using chromogenic media and confirmed by MALDI-TOF MS. Antifungal susceptibility testing followed CLSI M27-A4 broth microdilution guidelines for amphotericin B, fluconazole and 5-flucytosine. Gene expression of ERG2, ERG11 and MDR1 was evaluated by RT-qPCR after exposure to subinhibitory antifungal concentrations using the 2^−∆∆Ct method. Results: Candida albicans was the most frequent species, followed by Nakaseomyces glabratus, C. tropicalis and C. parapsilosis. Resistance varied among species, with elevated rates for fluconazole. ERG2 was notably overexpressed in amphotericin B-resistant isolates, while ERG11 and MDR1 showed species-dependent variation. Conclusions: Resistance mechanisms in Candida are species-specific and drug-dependent. Accurate species identification and understanding their molecular profiles are essential to guide targeted antifungal therapy and improve clinical outcomes.