Synergistic association of clioquinol with antifungal drugs against biofilm forms of clinical Fusarium isolates

Abstract

Summary Background The influence of biofilm on the complexity of fungal diseases has been reported in recent years, especially in non‐invasive mycoses such as keratitis and onychomycosis. The difficulty in treating cases of fusariosis in the human medical clinic exemplifies this situation, because when Fusarium spp. are present in the form of biofilm, the permeation of antifungal agents is compromised. Objectives This study proposes an association of clioquinol, an inhibitor of fungal cells with antifungal drugs prescribed to combat fusariosis in humans. Methods Susceptibility was assessed by microdilution in broth. Formation of biofilm by staining with violet crystal. Inhibition and removal of biofilm using the MTT colorimetric reagent. Time‐kill combination, hypoallergenicity test, cytotoxicity test and toxicity prediction by computer analysis were also performed. Results Clioquinol associated with voriconazole and ciclopirox inhibited biofilm formation. Possibly, clioquinol acts in the germination and elongation of hyphae, while voriconazole prevents cell adhesion and ciclopirox the formation of the extracellular polymeric matrix. The CLIO‐VRC association reduced the biofilm formation by more than 90%, while the CLIO‐CPX association prevented over 95%. None of the association was irritating, and over 90% of the leucocytes remained viable. Computational analysis does not reveal toxicity relevant to CLIO, whereas VRC and CPX showed some risks for systemic use, but suitable for topical formulations. Conclusions The combination of CLIO‐VRC or CLIO‐CPX proved to be a promising association strategy in the medical clinic, both in combating fungal keratitis and onychomycosis, since they prevent the initial process of establishing an infection, the formation of biofilm.

Antimicrobial activity of clioquinol and nitroxoline: a scoping review

“…Employing polymerase chain reaction (PCR) and broth microdilution, Alvarez and Sanhueza ( 2016 ) found optimal activity for clioquinol against Scedosporium dehoogii , an opportunistic soil-dwelling fungus, with variable MICs between 0.5 and 1 µg/mL. Employing similar techniques, Chaves et al ( 2020 ) found MICs between 0.5 and 2 µg/mL for clioquinol against Fusarium species, which also denotes excellent activity against the fungus. In addition, the research team also found excellent antibiofilm activity for clioquinol (MAC = 5–10 µg/mL) against isolated Fusarium species.…”

Competitiveness during Dual-Species Biofilm Formation of Fusarium oxysporum and Candida albicans and a Novel Treatment Strategy

“…More recently, some AMPs with known action against different microorganisms have been associated with conventional antimicrobial drugs to improve the action of these drugs and decrease microbial resistance [34,35].…”

Fungal Keratitis Treatment Using Drug-Loaded Hyaluronic Acid Microgels

“…solani and F. oxysporum, have been isolated from humans that instigate fungal keratitis on the ocular surface . Corneal ulcer causes endophthalmitis, enucleation, as well as persistent blindness because of veiling by the Fusarium fungus on the cornea .…”