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Description

Acanthamoeba castellanii causes a rare but serious ocular infection called Acanthamoeba keratitis. Risk factors for infection include contact with contaminated water and poor hygiene of contact lenses. The first-line treatment is comprised of a months-long schedule of antibiotics. However, in cases where pharmacological interventions fail to address the infection, surgery may be necessary, with the continued risk of potential vision loss. Consequently, new treatments are needed, whether new pharmacological agents or new combination therapies with current agents. As an aerobic parasite, Acanthamoeba synthesizes ergosterol as a cell membrane insert, and ergosterol biosynthesis inhibitors (EBIs), common in antifungal pharmaceuticals, could potentially fill that gap. The most common EBIs are of the azole drug class, which inhibit CYP51 (sterol 14α-demethylase). This study reviews the clinical usage of azole inhibitors of CYP51 in the management of Acanthamoeba keratitis.

Keywords:

Amoebic keratitis, Cornea, Ergosterol biosynthesis inhibitors, Eukaryotic pathogen, Eye infection

Disciplines

Eye Diseases | Infectious Disease | Medical Pharmacology | Ophthalmology | Parasitic Diseases | Primary Care

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Targeting CYP51 in the treatment of Acanthamoeba keratitis

Acanthamoeba castellanii causes a rare but serious ocular infection called Acanthamoeba keratitis. Risk factors for infection include contact with contaminated water and poor hygiene of contact lenses. The first-line treatment is comprised of a months-long schedule of antibiotics. However, in cases where pharmacological interventions fail to address the infection, surgery may be necessary, with the continued risk of potential vision loss. Consequently, new treatments are needed, whether new pharmacological agents or new combination therapies with current agents. As an aerobic parasite, Acanthamoeba synthesizes ergosterol as a cell membrane insert, and ergosterol biosynthesis inhibitors (EBIs), common in antifungal pharmaceuticals, could potentially fill that gap. The most common EBIs are of the azole drug class, which inhibit CYP51 (sterol 14α-demethylase). This study reviews the clinical usage of azole inhibitors of CYP51 in the management of Acanthamoeba keratitis.

Keywords:

Amoebic keratitis, Cornea, Ergosterol biosynthesis inhibitors, Eukaryotic pathogen, Eye infection