Unraveling drug penetration of echinocandin antifungals at the site of infection in an intra-abdominal abscess model
Open accessAbstract
Intra-abdominal candidiasis (IAC) is a prominent invasive fungal infection associated with high mortality. Prompt antifungal therapy and source control are crucial for successful treatment. Echinocandin antifungal drugs are first-line agents; however, their clinical effectiveness is highly variable, with known potential for breakthrough resistance, and little is known about drug exposure at the site of infection. Using matrix-assisted desorption ionization mass spectrometry imaging technology, we investigated the spatial and quantitative distribution in tissue lesions for two echinocandin drugs, micafungin and CD101, in a clinically relevant IAC mouse model. Drug accumulation within lesions was observed with both drugs at their humanized therapeutic doses. CD101, but not micafungin, accumulated in lesions at levels above the mutant prevention concentration of the infecting strain. These findings indicate that current echinocandin drugs are limited by penetration at the site of infection and have implications for clinical outcomes and emergence of resistance in patients with IAC.
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Rezafungin has a prolonged half-life of around 133 h that allows extended-interval dosing and provides high plasma drug concentrations early in therapy.
“Rezafungin has a prolonged half-life (around 133 h) that allows extended-interval dosing and provides high plasma drug concentrations early in therapy.”
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- Authors
- Zhao, Y., Prideaux, B., Nagasaki, Y., Lee, M. H., Chen, P.-Y., Blanc, L., Ho, H., Clancy, C. J., Nguyen, M. H., Dartois, V., & Perlin, D. S.
- Affiliations
- Rutgers Health (US)
- University of Pittsburgh (US)
- Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey, USA
- Corresponding author
- Zhao, Yanan
- Perlin, David S.
- ORCID
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 2017-10
- Volume
- 61
- Issue
- 10
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC5610477
- OpenAlex
- W2736416755
- Cited by
- 102
- References
- 43
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 14 · 2023: 11 · 2022: 9 · 2021: 14 · 2020: 16 · 2019: 8 · 2018: 8 · 2017: 5
- FWCI
- 7.79
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- HHS | National Institutes of Health (AI109025)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Pharmacology › Antibiotics Pharmacokinetics and Efficacy
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Keywords
- echinocandins, intra-abdominal candidiasis, micafungin, CD101, mutant prevention concentration, invasive fungal infections, mouse model
- MeSH terms
- Micafungin, Animals, Antifungal Agents, Candida albicans, Candidiasis, Disease Models, Animal, Female, Microbial Sensitivity Tests, Abdominal Abscess, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Drug Resistance, Fungal, Mice, Echinocandins, Lipopeptides
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