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Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
A clinical and molecular analysis of Candidozyma auris strains from Romania, 2022-2023
Marius Surleac1,2, Adriana Mihaela Stanciu2,3, Dragoș Florea2,3
1Research Institute of the University of Bucharest, University of Bucharest, Bucharest, Romania.
Abstract:
Candidozyma auris (formerly Candida auris; C. auris) raises significant concerns for healthcare facilities due to its ability to cause severe systemic infections, increased resistance to antifungals, and high intra-hospital transmissibility. We conducted a retrospective study on 102 patients diagnosed in 2022 and 2023. Demographic, clinical, and epidemiologic data were collected from the hospital databases. C. auris was identified using MALDI-TOF systems, and antifungal susceptibility was determined with Micronaut. The isolates were sequenced using Illumina next-generation sequencing platforms. Molecular epidemiology analysis was performed with multiple bioinformatics approaches (phylogenetic tools, resistance genes-related predictions, and variant analyses). Most patients (80/102) were admitted to or had been recently transferred from intensive care units at the moment of C. auris detection. Most cases (57/102) were classified as infections; 29 of them were bloodstream infections. All patients had been treated with broad-spectrum antibiotics before C. auris isolation, and 75/102 had received antifungals. All 31 tested isolates showed resistance to fluconazole, 5 were resistant to amphotericin B, and they were all susceptible to echinocandins. Crude mortality for infected patients was 68.18%. The 31 analyzed sequences belonged to clade I and bore multiple resistance markers.IMPORTANCEHighly antifungal-resistant Candidozyma auris keeps spreading in regions previously free of this pathogen, stressing once again the need for active surveillance, flexible control measures, and antimicrobial stewardship. This study is seminal for our understanding of the C. auris outbreak in Romania, providing insights into the evolutionary dynamics and genomic diversity of the pathogen and highlighting clade-specific mutations possibly linked to antifungal resistance. By joining these molecular characteristics with clinical, epidemiological, and microbiology data, such as risk factors for acquiring C. auris and phenotypic antifungal susceptibility, the study can be instrumental for surveillance and infection control strategies that are essential due to the pathogen's high transmissibility and the global health threat that it poses.
Insights
Candidozyma auris causes severe infections and is resistant to antifungals. This study of 102 patients reveals its spread and resistance patterns, highlighting the need for surveillance and control.
Area of Science:
- Medical Mycology
- Infectious Diseases
- Genomics
Background:
- Candidozyma auris (formerly Candida auris) poses a significant threat due to antifungal resistance and transmissibility.
- Healthcare facilities face challenges managing C. auris infections.
Purpose of the Study:
- To analyze the clinical, epidemiological, and molecular characteristics of C. auris infections.
- To understand the genomic diversity and antifungal resistance of C. auris isolates.
- To inform surveillance and infection control strategies.
Main Methods:
- Retrospective study of 102 patients diagnosed between 2022-2023.
- Identification using MALDI-TOF, antifungal susceptibility testing (Micronaut), and whole-genome sequencing (Illumina).
- Bioinformatic analysis including phylogenetic, resistance gene, and variant analyses.
Main Results:
- Most patients (80/102) were in intensive care units.
- All 31 tested isolates were resistant to fluconazole; 5 were resistant to amphotericin B.
- All isolates were susceptible to echinocandins; crude mortality was 68.18% for infected patients.
- Sequenced isolates belonged to clade I and showed multiple resistance markers.
Conclusions:
- C. auris outbreaks require active surveillance and robust infection control.
- Clade I isolates exhibit high antifungal resistance, necessitating tailored treatment strategies.
- Genomic insights are crucial for managing this emerging global health threat.
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