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Published on: December 28, 2017
Inter-Institutional Dynamics and Impact of Fluconazole-Resistant Candida parapsilosis
Maya Korem1,2, Shelly Reich3, Galia Rahav4,5
1Department of Clinical Microbiology and Infectious Diseases, Hadassah Medical Center, Jerusalem, Israel.
Background:
Infections with fluconazole-resistant Candida parapsilosis have been increasing in Israeli hospitals with unclear implications for patient outcomes.
Objectives:
To determine the frequency, mechanisms, molecular epidemiology, and outcomes of azole-resistant C. parapsilosis bloodstream infections in four hospitals in Israel.
Patients/Methods:
C. parapsilosis bloodstream isolates were collected at four hospitals in central Israel during varying periods from 2005 to 2022. Antifungal susceptibility testing was done using CLSI broth microdilution. Risk factors for fluconazole resistance were investigated using logistic regression. ERG11 gene sequencing was performed on all isolates. Genetic relatedness was determined using multilocus microsatellite genotyping. Clinical cure, microbiological eradication, and mortality rates were compared between fluconazole-susceptible and resistant isolates.
Results:
A total of 192 patient-specific C. parapsilosis isolates were analysed. Resistance to fluconazole and voriconazole was detected in 80 (41%) and 14 (7.2%) isolates, respectively. The ERG11 Y132F substitution was found in 91% of fluconazole-resistant and 1% of fluconazole-susceptible isolates. Increasing age, intensive care hospitalisation, haemodialysis, and recent exposure to antibiotics were risk factors for fluconazole-resistant C. parapsilosis. Distinct but related genotypes predominated at each centre, indicating extensive dissemination within hospitals and limited transmission among them. Fluconazole resistance was associated with increased likelihood of microbiological failure but no significant difference in clinical cure and mortality.
Conclusions:
We found high rates of fluconazole resistance in C. parapsilosis, attributable to nosocomial spread of hospital-specific clones bearing the Y132F substitution. Fluconazole resistance was associated with a higher risk of microbiological but not clinical failure. Strategies to limit nosocomial transmission of C. parapsilosis are needed.
Insights
Fluconazole-resistant Candida parapsilosis infections are increasing in Israeli hospitals. While resistance is linked to microbiological failure, clinical outcomes and mortality were not significantly different, highlighting the need for infection control.
Area of Science:
- Medical Mycology
- Infectious Diseases
- Antimicrobial Resistance
Background:
- Increasing incidence of fluconazole-resistant Candida parapsilosis bloodstream infections in Israeli hospitals.
- Unclear impact of azole resistance on patient outcomes.
Purpose of the Study:
- Determine the frequency, resistance mechanisms, molecular epidemiology, and clinical outcomes of azole-resistant C. parapsilosis bloodstream infections.
- Investigate risk factors associated with fluconazole resistance.
Main Methods:
- Collected and analyzed 192 C. parapsilosis isolates from four Israeli hospitals (2005-2022).
- Performed antifungal susceptibility testing, ERG11 gene sequencing, and multilocus microsatellite genotyping.
- Utilized logistic regression to identify risk factors and compared clinical outcomes between susceptible and resistant isolates.
Main Results:
- 41% of C. parapsilosis isolates were resistant to fluconazole, often associated with the ERG11 Y132F substitution.
- Identified increasing age, ICU stay, haemodialysis, and prior antibiotic use as risk factors for resistance.
- Nosocomial spread of hospital-specific clones was observed, with resistance linked to higher microbiological failure rates but not clinical outcomes or mortality.
Conclusions:
- High rates of fluconazole resistance in C. parapsilosis are driven by hospital-acquired infections with specific resistant clones.
- Fluconazole resistance increases the risk of microbiological treatment failure.
- Effective strategies are required to curb the nosocomial transmission of C. parapsilosis.
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