Inter-Institutional Dynamics and Impact of Fluconazole-Resistant Candida parapsilosis
Maya Korem
Department of Clinical Microbiology and Infectious Diseases, Hadassah Medical Center, Jerusalem, Israel
Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
Contribution: Conceptualization, Investigation, Methodology, Data curation, Validation, Formal analysis, Project administration, Writing - original draft, Writing - review & editing, Software, Supervision
Search for more papers by this authorShelly Reich
Infectious Diseases Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
Contribution: Investigation, Software, Formal analysis, Data curation
Search for more papers by this authorGalia Rahav
School of Medicine, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel
Infectious Diseases Unit and Laboratories, Sheba Medical Center, Ramat Gan, Israel
Contribution: Investigation, Writing - review & editing, Data curation
Search for more papers by this authorDafna Yahav
School of Medicine, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel
Infectious Diseases Unit, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel
Contribution: Investigation, Writing - review & editing, Data curation
Search for more papers by this authorMiriam Weinberger
School of Medicine, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel
Infectious Diseases Unit, Shamir (Assaf Harofeh) Medical Center, Zerifin, Israel
Contribution: Data curation, Writing - review & editing, Investigation
Search for more papers by this authorAnna Novikov
Infectious Diseases Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
Contribution: Investigation, Visualization, Validation
Search for more papers by this authorNaama Mizrahi
Infectious Diseases Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
Contribution: Investigation, Data curation, Software
Search for more papers by this authorCorresponding Author
Ronen Ben-Ami
Infectious Diseases Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
School of Medicine, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel
Correspondence:
Ronen Ben-Ami ([email protected])
Contribution: Conceptualization, Investigation, Writing - original draft, Methodology, Validation, Visualization, Writing - review & editing, Formal analysis, Project administration, Software, Data curation, Supervision, Resources
Search for more papers by this authorMaya Korem
Department of Clinical Microbiology and Infectious Diseases, Hadassah Medical Center, Jerusalem, Israel
Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
Contribution: Conceptualization, Investigation, Methodology, Data curation, Validation, Formal analysis, Project administration, Writing - original draft, Writing - review & editing, Software, Supervision
Search for more papers by this authorShelly Reich
Infectious Diseases Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
Contribution: Investigation, Software, Formal analysis, Data curation
Search for more papers by this authorGalia Rahav
School of Medicine, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel
Infectious Diseases Unit and Laboratories, Sheba Medical Center, Ramat Gan, Israel
Contribution: Investigation, Writing - review & editing, Data curation
Search for more papers by this authorDafna Yahav
School of Medicine, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel
Infectious Diseases Unit, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel
Contribution: Investigation, Writing - review & editing, Data curation
Search for more papers by this authorMiriam Weinberger
School of Medicine, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel
Infectious Diseases Unit, Shamir (Assaf Harofeh) Medical Center, Zerifin, Israel
Contribution: Data curation, Writing - review & editing, Investigation
Search for more papers by this authorAnna Novikov
Infectious Diseases Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
Contribution: Investigation, Visualization, Validation
Search for more papers by this authorNaama Mizrahi
Infectious Diseases Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
Contribution: Investigation, Data curation, Software
Search for more papers by this authorCorresponding Author
Ronen Ben-Ami
Infectious Diseases Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
School of Medicine, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel
Correspondence:
Ronen Ben-Ami ([email protected])
Contribution: Conceptualization, Investigation, Writing - original draft, Methodology, Validation, Visualization, Writing - review & editing, Formal analysis, Project administration, Software, Data curation, Supervision, Resources
Search for more papers by this authorFunding: This study was supported by Israeli Science Foundation and Bridging fund of Hadassah Medical Center.
ABSTRACT
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.
Conflicts of Interest
RB has received consulting fees from Merck & Co., GSK and Baccine, and research support from the Israeli Science Foundation (442/18) MK has received bridging funds of the Hadassah Medical Centre (6080302). Other authors: nothing to disclose.
Open Research
Data Availability Statement
The data that supports the findings of this study are available in the Supporting Information of this article.
Supporting Information
| Filename | Description |
|---|---|
| myc70017-sup-0001-DataS1.zipZip archive, 361.3 KB |
Data S1. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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