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. 2025 Mar;56(1):341-352.
doi: 10.1007/s42770-024-01611-8. Epub 2025 Jan 16.

Antifungal susceptibility, clinical findings, and biofilm resistance of Fusarium species causing keratitis: a challenge for disease control

Pedro de Freitas Santos Manzi de Souza  1 , Edlâny Pinho Romão Milanez  1   2 , Ana Raquel Colares de Andrade  1 , Lua Silva  1 , Maria Laína Silva  1 , Ruan Costa Monteiro  3 , Anderson Messias Rodrigues  3 , Débora Castelo Branco de Souza Collares Maia  1 , Glaucia Morgana de Melo Guedes  1 , Rossana de Aguiar Cordeiro  4
Affiliations

Antifungal susceptibility, clinical findings, and biofilm resistance of Fusarium species causing keratitis: a challenge for disease control

Pedro de Freitas Santos Manzi de Souza et al. Braz J Microbiol. 2025 Mar.

Abstract

Fusarium keratitis (FK) is an important clinical condition that can lead to blindness and eye loss, and is most commonly caused by the Fusarium solani species complex (FSSC). This study evaluated the susceptibility of planktonic cells and biofilms of FSSC (n = 7) and non-FSSC (n = 7) isolates obtained from patients with keratitis from a semi-arid tropical region to amphotericin B (AMB), natamycin (NAT), voriconazole (VRZ), efinaconazole (EFZ), and luliconazole (LCZ). Analysis of clinical data showed that trauma was the most common risk factor for FK patients. Disease onset was longer in non-FSSC group (3-30 days) than in the FSSC group (3-7 days). FSSC strains were less susceptible to AMB and VRZ than non-FSSC strains (p < 0.05). Susceptibility to NAT, LCZ and EFZ was similar between isolates of FSSC and non-FSSC groups. Overall, patients infected with non-FSSC showed a better response to antifungal treatment. Corneal transplantation was more common in patients infected with FSSC (3/7) than in those infected with non-FSSC (1/7). Mature biofilms showed a poor response to antifungal treatment. Patients infected with Fusarium strains capable of forming antifungal tolerant biofilms had more complex therapeutic management, requiring two antifungals and/or corneal transplantation (p < 0.05). This study highlights the importance of mycological diagnosis and the antifungal susceptibility testing in the clinical management of FK. The ability of Fusarium to form antifungal tolerant biofilms poses a challenge to clinicians and urges the development of new antibiofilm therapeutics.

Keywords: Efinaconazole; Fungal keratitis; Luliconazole Fusarium solani species complex.

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Conflict of interest statement

Declarations. Ethics statement: The authors confirm that the ethical policies of the journal, as noted on the journal’s author guidelines page, have been adhered to and the appropriate ethical review committee approval has been received. The institutional ethics committee of the Federal University of Ceara’s guidelines were followed. Conflict of interest: None to declare.

Figures

Fig. 1
Fig. 1
Minimum inhibitory concentration (MIC) and Relative Minimum inhibitory concentration of antifungals against Fusarium strains FSSC: Fusarium solani species complex; AMB: amphotericin B; NAT: natamycin; VRZ: voriconazole. Asterisks indicate statistical significance (p < 0.05)
Fig. 2
Fig. 2
Biofilm forming ability of non-FSSC (Fusarium solani species complex) and FSSC strains. Dotted line indicates the cut-off that classifies the strains as strong biofilm producers FSSC: Fusarium solani species complex
Fig. 3
Fig. 3
CLSM images of Fusarium biofilms (strain 4578-27). Antifungals were added during adhesion stage or after biofilm maturation. Biofilms were formed on Thermanox® slides in RPMI 1640 medium without antifungals as controls (A1, A2) or supplemented with AMB (B1), NAT (C1), VRZ (D1), EFZ (E1), or LCZ (F1). Mature biofilms were treated AMB (B2), NAT (C2), VRZ (D2), EFZ (E2), or LCZ (F2). SYTO9 shows live cells (green) at 488 nm; propidium iodide shows dead or damaged cells (red) at 561 nm. Magnification: CLSM, 400x; Bar: 50 μm
See this image and copyright information in PMC

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