Breakthrough Bloodstream Infections Caused by Echinocandin-Resistant Candida tropicalis: An Emerging Threat to Immunocompromised Patients with Hematological Malignancies
Open accessAbstract
Background. Candida tropicalis is a virulent fungal pathogen for which echinocandins are the primary therapy. Emergence of resistance to echinocandins of C. tropicalis carries potentially ominous therapeutic implications. Methods. We describe herein two patients with breakthrough C. tropicalis fungemia during echinocandin therapy, characterize their molecular mechanism of resistance, and systematically review 13 previously reported cases of echinocandin-resistant C. tropicalis bloodstream infections (BSIs) and other diseases. Results. Among these 15 patients with echinocandin-resistant C. tropicalis infections, the median age was 61 years (ages 28–84 years) and 13 (86%) were immunocompromised. Thirteen (86%) of all patients had a history of pervious or concurrent exposure to echinocandins. Isolates of C. tropicalis from 11 cases, including the two index cases, underwent DNA sequencing of the FKS1 gene for mutations known to confer echinocandin resistance. The amino acid substitution Ser654Pro was shown in four cases, while other FKS1 mutations encoded Ser80S/Pro, Phe641Leu, Phe641Ser, Ser80S/Pro substitutions. These mutational events were not associated with collateral increases in minimum inhibitory concentrations to antifungal triazoles and amphotericin B. Overall mortality in patients with echinocandin-resistant C. tropicalis infections was 40%. Among those six patients who died, two received monotherapy with voriconazole, one was treated with fluconazole, one remained on caspofungin, and two were switched to liposomal amphotericin B. Nine patients (60%) survived after being treated with an antifungal agent other than an echinocandin. Conclusions. Emergence of resistance to echinocandins by C. tropicalis, occurs during antifungal therapy, is associated with high mortality, is mediated by a diverse range of FKS1 mutations, retains in vitro susceptibility to triazoles and amphotericin B, and constitutes an emerging threat to patients with hematological malignancies.
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A review of the most recent data suggests that many, but not all, breakthrough Candida infections occur due to organisms that are resistant to one or more antifungals, and are dominated by non-albicans Candida species, especially C. glabrata, C. krusei, C. parapsilosis, and C. tropicalis.
“A review of the most recent data pertaining to BT Candida infections suggests that many, but not all, of these infections occur due to organisms that are resistant to one or more antifungals, and accordingly are dominated by non-albicans Candida species, especially C. glabrata, C. krusei, C. parapsilosis, and C. tropicalis.89–92”
From Epidemiology of Invasive Candidiasis (2024) · cites this paper as [89]
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- Authors
- Sfeir, M. M., Jiménez-Ortigosa, C., Gamaletsou, M. N., Schuetz, A. N., Soave, R., Van Besien, K., Small, C. B., Perlin, D. S., & Walsh, T. J.
- Affiliations
- NewYork–Presbyterian Hospital (US)
- Public Health Research Institute, New Jersey Medical School/Rutgers Biomedical and Health Sciences, Newark, NJ 07103, USA
- National and Kapodistrian University of Athens (GR)
- Mayo Clinic (US)
- Division of Hematology/Oncology, Weill Cornell Medicine and New York Presbyterian Hospital, New York, NY 10065, USA
- Rutgers Health (US)
- Corresponding author
- Walsh, Thomas J.
- ORCID
- Venue
- Journal of Fungi
- Publisher
- MDPI AG
- Published
- 2020-01-31
- Volume
- 6
- Issue
- 1
- Pages
- 20
- ISSN
- 2309-608X (ISSN-L)
- PMC
- PMC7151208
- OpenAlex
- W3004181044
- Cited by
- 19
- References
- 24
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 3 · 2023: 2 · 2022: 3 · 2021: 3
- FWCI
- 0.26
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- Journal of Fungi (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (2r01ai109025-11)
- National Institute of Allergy and Infectious Diseases (R01AI-109025)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- Candida tropicalis, echinocandin resistance, bloodstream infection, FKS1 mutations, immunocompromised patients, hematologic malignancies, antifungal therapy, amphotericin B susceptibility, voriconazole, caspofungin, liposomal amphotericin B, mortality
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