Paradoxical Growth Effect of Echinocandins in Fungal Biofilms: A Literature Review on Mechanisms, Species Specificity, and Clinical Relevance

Ayu Nazilla Fatimahtus Zahra¹, Pepy Dwi Endraswari²*, Dwi Murtiastutik³

Abstract

The paradoxical growth (PG) effect, also termed the Eagle-like effect, describes the resumption of fungal growth at echinocandin concentrations above the minimum inhibitory concentration (MIC), contrary to the expected dose-dependent inhibition. Although documented for nearly two decades, the relevance of PG to biofilm-associated infections and its clinical significance remain incompletely understood. This literature review examines the evidence for PG in fungal biofilms, encompassing both Candida and Aspergillus species, with emphasis on mechanisms, species-specific prevalence, and therapeutic implications. A narrative literature review was conducted by searching PubMed and Scopus for studies published between 2004 and 2025, with priority given to the last decade. The evidence indicates that PG occurs in sessile cells of multiple Candida species, with prevalence varying by species and echinocandin type; C. parapsilosis and C. albicans exhibit the highest rates with caspofungin, whereas C. glabrata appears uniformly non-paradoxical. In Aspergillus fumigatus, PG is observed with caspofungin but not consistently with micafungin or anidulafungin. Mechanistically, PG involves compensatory cell wall remodeling, particularly chitin deposition, and activation of stress-response pathways including calcineurin and Hsp90. Recent evidence implicates segmental aneuploidy as a reversible adaptive mechanism in C. albicans. Farnesol eliminates PG in vitro, suggesting a potential adjunctive strategy. The clinical relevance of PG remains uncertain due to limited in vivo confirmation and the high drug concentrations required in vitro. Standardized detection methods and clinical correlation studies are needed before treatment recommendations can be modified.

Keywords

paradoxical growth; Eagle effect; echinocandin; fungal biofilm; Candida; Aspergillus

Cite This Article

Zahra, A. N. F., Endraswari, P. D., Murtiastutik, D. (2026). Paradoxical Growth Effect of Echinocandins in Fungal Biofilms: A Literature Review on Mechanisms, Species Specificity, and Clinical Relevance. International Journal of Scientific Advances (IJSCIA), Volume 7| Issue 6: Nov – Dec 2026, Pages 970-974. URL: https://www.ijscia.com/wp-content/uploads/2026/11/Volume7-Issue6-Nov-Dec-No.1119-970-974.pdf

Volume 7 | Issue 6: Nov – Dec 2026