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Review
. 2019 Jan/Feb;35(1):6-22.
doi: 10.1089/jop.2018.0089. Epub 2018 Nov 8.

Challenges in the Polyene- and Azole-Based Pharmacotherapy of Ocular Fungal Infections

Prit Lakhani  1   2 , Akash Patil  1   2 , Soumyajit Majumdar  1   2
Affiliations
Review

Challenges in the Polyene- and Azole-Based Pharmacotherapy of Ocular Fungal Infections

Prit Lakhani et al. J Ocul Pharmacol Ther. 2019 Jan/Feb.

Abstract

Polyenes and azoles constitute 2 major drug classes in the antifungal armamentarium used to treat fungal infections of the eye such as fungal keratitis, endophthalmitis, conjunctivitis, and blepharitis. These classes of drugs have come to occupy an important niche in ophthalmic antifungal therapy due to their broad spectrum of activity against a variety of filamentous and yeast-like fungi. Natamycin suspension (Natacyn®), a polyene antifungal drug, is currently the only US FDA-approved formulation for treating ophthalmic fungal infections, whereas the other polyene and azole antifungals such as amphotericin B, fluconazole, itraconazole, ketoconazole, miconazole, voriconazole, and posaconazole are routinely used off-label in the clinical setting. Despite potent antifungal activity, the clinical utility of these agents in ophthalmic infections has been challenged by their physicochemical properties, the unique ocular anatomy and physiology, selective antifungal activity, ocular and systemic toxicity, emergence of resistance and cross-resistance, and absence of reliable techniques for developing a robust in vitro-in vivo correlation. This review discusses the aforementioned challenges and the common approaches undertaken to circumnavigate the difficulties associated with the polyene- and azole-based pharmacotherapy of ophthalmic fungal infections.

Keywords: anti-infectives; keratitis; ocular fungal infections; ocular pharmacotherapy; polyene and azole antifungals.

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Conflict of interest statement

No competing financial interests exist.

Figures

<b>FIG. 1.</b>
FIG. 1.
(i) Amphotericin B, (ii) Natamycin; [(A): Conjugated multiple bonds, (B): Mycosamine moiety, (C): Carboxylic group].
<b>FIG. 2.</b>
FIG. 2.
(i) Miconazole, (ii) Ketoconazole, (iii) Fluconazole, (iv) Posaconazole, (v) Itraconazole, (vi) Voriconazole; [(A): Imidazole, (B): 1,2,4-triazole].
<b>FIG. 3.</b>
FIG. 3.
Mechanism of action of polyene and azole antifungal drugs in fungal cells.
<b>FIG. 4.</b>
FIG. 4.
Schematic representation of the development of resistance against polyene and azole antifungals manifested in fungal species. CDR, confluence-dependent resistance; MDR, multidrug resistance.
<b>FIG. 5.</b>
FIG. 5.
Brief overview on the anatomical and physiological ocular barriers that compromise the ocular pharmacokinetics of the drugs.
See this image and copyright information in PMC

References

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