Acanthamoeba Keratitis: an update on amebicidal and cysticidal drug screening methodologies and potential treatment with azole drugs

ABSTRACT

Introduction: Acanthamoeba encompasses several species of free-living ameba encountered commonly throughout the environment. Unfortunately, these species of ameba can cause opportunistic infections that result in Acanthamoeba keratitis, granulomatous amebic encephalitis, and occasionally systemic infection.

Areas covered: This review discusses relevant literature found through PubMed and Google scholar published as of January 2021. The review summarizes current common Acanthamoeba keratitis treatments, drug discovery methodologies available for screening potential anti-Acanthamoeba compounds, and the anti-Acanthamoeba activity of various azole antifungal agents.

Expert opinion: While several biguanide and diamidine antimicrobial agents are available to clinicians to effectively treat Acanthamoeba keratitis, no singular treatment can effectively treat every Acanthamoeba keratitis case.Efforts to identify new anti-Acanthamoeba agents include trophozoite cell viability assays, which are amenable to high-throughput screening. Cysticidal assays remain largely manual and would benefit from further automation development. Additionally, the existing literature on the effectiveness of various azole antifungal agents for treating Acanthamoeba keratitis is incomplete or contradictory, suggesting the need for a systematic review of all azoles against different pathogenic Acanthamoeba strains.

KEYWORDS:

• Acanthamoeba
• amebicidal
• antifungal
• assay
• azole
• cell viability
• cysticidal
• drug screening
• drugs
• keratitis treatments

Article Highlights

• Acanthamoeba spp. are causative agents of Acanthamoeba keratitis, granulomatous amebic encephalitis, and systemic infections.

• Acanthamoeba keratitis treatments heavily rely on a combination of biguanide and diamidine antimicrobial agents, but other antiseptic, antiparasitic, photodynamic, antibiotic, and antifungal drugs have been evaluated as potential treatment options.

• Azole antifungal agents are well tolerated in patients and have varying levels of trophocidal and cysticidal activity.

• Several azole antifungal agents have been tested in limited cases of Acanthamoeba keratitis. Further evaluation is needed to determine the ocular bioavailability and effectiveness of azole therapy for Acanthamoeba keratitis.

• Several high-throughput cell viability assays exist for identifying trophocidal compounds while cysticidal assays rely on manual observation or trypan blue staining.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

A Debnath was supported by the grant R21AI146460 from NIH.