In vitro susceptibility of Aspergillus and Fusarium associated with equine keratitis to new antifungal drugs

Abstract

Objective To determine minimum inhibitory concentrations (MICs) of four fungal species isolated from horses presented with equine fungal keratitis (EFK) in the southeastern United States to previously untested azole, echinocandin, and carboxamide antifungal drugs. Methods In vitro assays were performed to determine the susceptibility of Aspergillus flavus, A. fumigatus, Fusarium falciforme, and F. keratoplasticum to five antifungal drugs representing three modes of action. Results Luliconazole exhibited increased growth inhibition against both Aspergillus and Fusarium compared to commonly used, standard antifungal drugs. MIC values for luliconazole at 0.001‐0.002 µg/mL were at least 25‐fold lower than all other antifungal drugs tested, including voriconazole. Conclusions The increased antifungal activity of luliconazole observed in this study warrants further investigation for its potential as an antifungal drug for equine fungal keratitis.

Case Report: Successful Management of Refractory Keratomycosis in an Alpaca Using Penetrating Keratoplasty and Combination Antifungal Therapy (Caspofungin 0.5% and Terbinafine 1%)

“…Caspofungin penetrates through the cornea with a compromised epithelium (but not intact), resulting in aqueous humor drug levels above MICs for most fungi (21). Caspofungin has variable but sometimes good efficacy against Scopulariopsis sp., variable but sometimes good efficacy against Fusarium sp., shows no signs of corneal toxicity or irritation, and is intermediate cost to the client (7,8,15,21,25). No adverse reactions to any topical medications were noted in this case.…”

In vitro antifungal susceptibility ofFusariumspecies andAspergillus fumigatuscultured from eleven horses with fungal keratitis

“…Voriconazole can penetrate intact corneal epithelium which provides a major advantage in treatment of equine fungal keratitis and fungal abscesses 31 . A recent study investigated MICs of two Aspergillus species and two Fusarium species to voriconazole, pydiflumetofen, prothioconazole, caspofungin, and a novel azole, luliconazole 35 . They found that luliconazole had an increased growth inhibition and a 25‐fold lower MICs compared with other antifungals for both organisms 35 .…”

“…A recent study investigated MICs of two Aspergillus species and two Fusarium species to voriconazole, pydiflumetofen, prothioconazole, caspofungin, and a novel azole, luliconazole 35 . They found that luliconazole had an increased growth inhibition and a 25‐fold lower MICs compared with other antifungals for both organisms 35 . Further clinical investigations of this novel azole in the clinical setting is required 35 …”

Fungal keratitis in a mare: case report in Costa Rica

“…Several fungal genera are associated with keratomycosis, including Aspergillus, Fusarium, Candida, Curvularia, Penicillium, Cylindrocarpon, and Mucor (Galán et al 2009;Utter et al 2010;Galera & Brooks 2012;Wada et al 2013;Samanta 2015;Sherman et al 2017;Ledbetter et al 2018), the first two being the most frequently reported and with the worst prognosis (Galán et al 2009;Utter et al 2010;Cafarchia et al 2013;Sherman et al 2017;Roberts et al 2020). Since these genera are also found in healthy eyes (Khosravi et al 2014), a fungal culture must be conducted with histopathology and/or cytology to verify whether the tissue has been compromised with hyphae or yeast.…”

“…Antifungal resistance is a concerning threat to fighting mycotic diseases such as the one discussed here. New drugs such as luliconazole (an imidazole used to treat keratomycosis in humans) have become a potential treatment for this disease caused by resistant Aspergillus or Fusarium species in horses, by exhibiting the lowest MICs (Minimum Inhibitory Concentrations) in antifungal susceptibility tests (Roberts et al 2020). However, its availability and price are restrictive to developing nations, highlighting the importance of implementing the proper treatment in the early stages of the disease.…”