Abstract
Background
Invasive fungal infections (IFIs) represent a growing health concern due to their morbidity and mortality. The extensive use of antifungal medications contributed to an increase in fungal resistance, particularly among non- albicans Candida species, such as C. parapsilosis (CP). The World Health Organization (WHO) identified fluconazole-resistant C. parapsilosis (FLRCP) as a priority pathogen in the fight against antimicrobial resistance, but data on its clinical impact and risk factors compared to fluconazole-sensitive strains remains limited. This study evaluates the prevalence, risk factors, clinical impact and outcomes of patients infected with FLRCP.
Methods
This retrospective, single-center study involved patients with invasive candidiasis caused by C. parapsilosis who were admitted to Policlinico Umberto I in Rome between April 2020 and May 2024. Patients were divided into two groups according to the fluconazole (FLZ) resistance of C. parapsilosis. Minimum inhibitory concentration (MIC) for antifungals were measured using microdilution testing and susceptibility was assessed according to EUCAST clinical breakpoints (resistant to FLZ defined as MIC > 4 mg/L). Data analysis was conducted using R-4.4.0 statistical software.
Results
In a cohort of 108 patients, the prevalence of FLRCP was 52% (n = 56), with 50% of the cases from the intensive care unit (ICU). The analysis revealed a statistically significant association between FLRCP and prior ICU admission (P-value 0.01), identified also as the only independent predictive factor for fluconazole resistance (OR 3.65, P-value 0.02). Of note, no significant association was found between FLRCP and previous antifungal therapy, including azoles. Thirty-one percent of patients with FLRCP received liposomal amphotericin B, while 69% were treated with caspofungin, without significant difference between survivors and non-survivors. Resistance to fluconazole did not significantly affect clinical impact or patient outcomes (Table 1).
Conclusions
Although evidence on the clinical impact of FLRCP remains limited, the increase in cases, as reflected in our prevalence data, highlights the urgent need to define its pathogenic role. Horizontal transmission of the pathogen, suggested by intra-hospital outbreaks involving genetically related clusters and azole-naive patients, emphasizes the need for an Anti-Fungal Stewardship (AFS) program to limit spread and prevent further fungal resistance.
Table 1.
General descriptive analysis and association analysis for fluconazole resistance and multivariable logistic regression model for predictors of fluconazole resistance