The eagle-like effect of echinocandins: what’s in a name?
Abstract
Despite several years of research, a lot of questions remain about the paradoxical attenuation of echinocandin activity against Candida and Aspergillus species at certain drug concentrations above the MIC values, the so-called paradoxical growth effect or Eagle-like effect. Although this phenomenon has been observed in several in vitro studies, confirming in vivo data are scarce. The clinical relevance remains unknown, although more and more data suggest that the clinical impact of this phenomenon might be heavily overrated. Detailed knowledge about the mechanisms responsible for this phenomenon and further research about the presence of the effect in the human body is necessary to decide whether the paradoxical growth effect of echinocandins can really interfere with an adequate treatment of invasive fungal diseases in clinical practice.
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The paradoxical effect, also known as the Eagle effect, often observed with echinocandins may be confused with antifungal persistence because the drugs show reduced activity in vitro at higher concentrations.
“Notably, the paradoxical effect, also known as the “Eagle effect”, often observed in echinocandins may confused with antifungal persistence, as the drugs show reduced activity in vitro at higher concentrations [40,41].”
From Antifungal persistence: Clinical relevance and mechanisms (2025) · cites this paper as [40]
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The Effects of an Hsp90 Inhibitor on the Paradoxical Effect
Kaneko, Y., Ohno, H., Imamura, Y., Kohno, S., & Miyazaki, Y. (2009) · Japanese Journal of Infectious Diseases · doi:10.7883/yoken.jjid.2009.392 · Cited by 23 · see citing works
Pharmacokinetics of caspofungin in a critically ill patient with liver cirrhosis
Spriet, I., Meersseman, W., Annaert, P., Hoon, J. N. J. M. D., & Willems, L. (2011) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-011-1066-8 · Cited by 22 · see citing works
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Killing Kinetics of Four Quinolones against Gram-Positive Cocci
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Paradoxical effect of antibiotics
SHAH, P. M. (1982) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/10.4.259 · Cited by 21 · see citing works
Intraocular Penetration of Micafungin in Patient with Candida albicans Endophthalmitis
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Bayegan, S., Majoros, L., Kardos, G., Kemény-Beke, A., Miszti, C., Kovacs, R., & Gesztelyi, R. (2010) · The Journal of Microbiology · doi:10.1007/s12275-010-9221-y · Cited by 21 · see citing works
Mariné, M., Pastor, F. J., Sahand, I. H., Pontón, J., Quindós, G., & Guarro, J. (2009) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00980-09 · Cited by 20 · see citing works
Szilágyi, J., Földi, R., Bayegan, S., Kardos, G., & Majoros, L. (2012) · Journal of Chemotherapy · doi:10.1179/1120009x12z.0000000005 · Cited by 18 · see citing works
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Micafungin Concentrations in the Plasma and Burn Eschar of Severely Burned Patients
Sasaki, J., Yamanouchi, S., Kudo, D., Endo, T., Nomura, R., Takuma, K., Kushimoto, S., Shinozawa, Y., Kishino, S., Hori, S., et al. (2011) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.05381-11 · Cited by 16 · see citing works
In-vitro activity of pefloxacin compared to other antibiotics
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Plasma concentration of micafungin in patients with hematologic malignancies
Nakagawa, Y., Suzuki, K., Ichii, Y., Saeki, Y., Kodaka, M., & Kishino, S. (2007) · Journal of Infection and Chemotherapy · doi:10.1007/s10156-006-0496-1 · Cited by 16 · see citing works
Paradoxical effect of antibiotics
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Ku, T. S. N., Bernardo, S. M., & Lee, S. A. (2011) · Journal of Medical Microbiology · doi:10.1099/jmm.0.032235-0 · Cited by 13 · see citing works
Immunological Aspects ofCandidaandAspergillusSystemic Fungal Infections
Mueller-Loebnitz, C., Ostermann, H., Franzke, A., Loeffler, J., Uharek, L., Topp, M. S., & Einsele, H. (2013) · Interdisciplinary Perspectives on Infectious Diseases · doi:10.1155/2013/102934 · Cited by 13 · see citing works
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Pharmacokinetics of Caspofungin in Two Patients with Burn Injuries
Jullien, V., Blanchet, B., Benyamina, M., Tod, M. M., & Vinsonneau, C. (2012) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00039-12 · Cited by 9 · see citing works
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Pharmacokinetics of antifungal drugs: practical implications for optimized treatment of patients
Bellmann, R., & Smuszkiewicz, P. (2017) · Infection · doi:10.1007/s15010-017-1042-z · Cited by 399 · see citing works
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Understanding Echinocandin Resistance in the Emerging Pathogen Candida auris
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Fungal persister cells: The basis for recalcitrant infections?
Wuyts, J., Van Dijck, P., & Holtappels, M. (2018) · PLOS Pathogens · doi:10.1371/journal.ppat.1007301 · Cited by 136 · see citing works
Antifungal Pharmacokinetics and Pharmacodynamics
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Vanreppelen, G., Wuyts, J., Dijck, P. V., & Vandecruys, P. (2023) · Journal of Fungi · doi:10.3390/jof9020171 · Cited by 112 · see citing works
The eagle effect and antibiotic-induced persistence: two sides of the same coin?
Prasetyoputri, A., Jarrad, A. M., Cooper, M. A., & Blaskovich, M. A. T. (2019) · Trends in Microbiology · doi:10.1016/j.tim.2018.10.007 · Cited by 101 · see citing works
Antifungal Susceptibility Testing: A Primer for Clinicians
Wiederhold, N. P. (2021) · Open Forum Infectious Diseases · doi:10.1093/ofid/ofab444 · Cited by 80 · see citing works
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In vitro antibacterial effects of statins against bacterial pathogens causing skin infections
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“Notably, the paradoxical effect, also known as the “Eagle effect”, often observed in echinocandins may confused with antifungal persistence, as the drugs show reduced activity in vitro at higher concentrations [40,41].”
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Combined Effect of Platelets and Anidulafungin against Aspergillus fumigatus Infections
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FIRST REPORT OF CANDIDA AURIS IN VIETNAMPreprint
Truong-Thien, P., Tuan, A. N., & Nguyen, T. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.05.12.653631
Owusu, E., Savani, S., & Redfern, R. L. (2025) · Neotropical Entomology · doi:10.1007/s13744-025-01306-1
Cristy, S. A., Walker, J. N., & Lorenz, M. C. (2026) · mBio · doi:10.1128/mbio.01785-26
- Authors
- Vanstraelen, K., Lagrou, K., Maertens, J., Wauters, J., Willems, L., & Spriet, I.
- Affiliations
- Universitair Ziekenhuis Leuven (BE)
- Corresponding author
- Vanstraelen, Kim
- Venue
- Expert Review of Anti-infective Therapy
- Publisher
- Informa UK Limited
- Published
- 2013-11
- Volume
- 11
- Issue
- 11
- Pages
- 1179-1191
- ISSN
- 1478-7210 (ISSN-L)
- 1744-8336
- OpenAlex
- W2108557541
- Cited by
- 28
- References
- 118
- Citations by year
- 2026: 1 · 2025: 4 · 2023: 2 · 2022: 4 · 2021: 2 · 2019: 3 · 2018: 5 · 2017: 3 · 2016: 2 · 2014: 2
- FWCI
- 0.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Expert Review of Anti-infective Therapy (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
- Keywords
- echinocandins, Candida, Aspergillus, invasive fungal infections, antifungal resistance, minimum inhibitory concentration
- MeSH terms
- Animals, Aspergillosis, Aspergillus, Candida, Candidiasis, Disease Models, Animal, Humans, Microbial Sensitivity Tests, Echinocandins
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