Clinical utility of caspofungin eye drops in fungal keratitis

Neoh, Chin Fen; Daniell, Mark; Chen, Sharon C.-A.; Stewart, Kay; Kong, David Chee Ming

doi:10.1016/j.ijantimicag.2014.04.008

Cited by 30 publications

(19 citation statements)

References 141 publications

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“…Therapeutic success depends on factors such as the ability of a topical antifungal agent to penetrate tissues. In some cases, oral antifungals are required to achieve this goal . However, until now, animal studies are inconclusive to determine the best treatment choice for fusariosis …”

Section: Introductionmentioning

confidence: 99%

Allylic Selenocyanates as New Agents to Combat Fusarium Species Involved with Human Infections

et al. 2017

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Fusarium is an emerging opportunistic fungal pathogen that causes local or systemic infections. The successful use of a therapeutic drug or combination antifungal therapies against Fusarium spp. are compromised because reports of multidrug resistance are currently frequent. Thus, the development of new antifungal capable of combating multidrug‐resistant Fusarium strains becomes necessary. This study presents the synthesis of seven new allylic selenocyanates and their screening against Fusarium spp. Minimum inhibitory concentrations (MICs) of these compounds ranged from 4 to 64 μg mL−1, with the mechanism of action being related to fungal cell membrane disruption. Specific structural changes, such as widespread thinning along the hyphae, were observed by scanning electron microscopy. The effect of selenocyanates on cell viability and genotoxicity are concentration dependent, however they did not cause mutagenicity in human cells. Five selenocyanates were identified as nonirritant by the ex‐vivo HET‐CAM (Hen′s Egg Test‐Chorioallantoic Membrane) method. Allylic selenocyanates represents a promising alternative in the treatment and prevention of fusariosis.

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Section: Introductionmentioning

confidence: 99%

Allylic Selenocyanates as New Agents to Combat Fusarium Species Involved with Human Infections

et al. 2017

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“…Similarly, itraconazole (doses above 10 mg injected intravitreally in rabbits) and voriconazole (400 mg b.i.d, orally in fungal keratitis patients) are known to cause retinal necrosis and visual disturbances, respectively. [122][123][124] Systemic side effects/toxicities such as nephrotoxicity (amphotericin B), hepatotoxicity (ketoconazole and voriconazole), and gastrointestinal upsets (itraconazole) are also commonly encountered upon their oral and/or intravenous administration in ocular fungal infections. 87,[124][125][126] Hence, from the abovementioned discussion, ocular and systemic toxicities evidently present an important aspect of the challenge in the ocular delivery of these agents.…”

Section: Figmentioning

confidence: 99%

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

Lakhani

Patil

Majumdar

2019

Journal of Ocular Pharmacology and Therapeutics

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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 Ò), 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 vitroin 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.

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“…Recent studies have suggested an increasing prevalence of disease 7. In contrast, it is relatively uncommon in developed nations (Australia and the UK), accounting for only 1–5% of all infectious keratitis presentations 5. Mycotic keratitis is most frequently associated with either filamentous ( Fusarium spp , Aspergillus spp , Penicillium spp and Curvularia spp) or yeast-like fungi ( Candida albicans and other Candida species) 8 9.…”

Section: Introductionmentioning

confidence: 99%

Multidrug-resistantFusariumkeratitis: diagnosis and treatment considerations

2016

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Mycotic keratitis is an ocular infective process derived from any fungal species capable of corneal invasion. Despite its rarity in developed countries, its challenging and elusive diagnosis may result in keratoplasty or enucleation following failed medical management. Filamentous fungi such as Fusarium are often implicated in mycotic keratitis. Bearing greater morbidity than its bacterial counterpart, mycotic keratitis requires early clinical suspicion and initiation of antifungal therapy to prevent devastating consequences. We describe a case of multidrug-resistant mycotic keratitis in a 46-year-old man who continued to decline despite maximal therapy and therapeutic keratoplasty. Finally, enucleation was performed as a means of source control preventing dissemination of a likely untreatable fungal infection into the orbit. Multidrug-resistant Fusarium is rare, and may progress to endophthalmitis. We discuss potential management options which may enhance diagnosis and outcome in this condition.

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Clinical utility of caspofungin eye drops in fungal keratitis

Cited by 30 publications

References 141 publications

Allylic Selenocyanates as New Agents to Combat Fusarium Species Involved with Human Infections

Allylic Selenocyanates as New Agents to Combat Fusarium Species Involved with Human Infections

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

Multidrug-resistantFusariumkeratitis: diagnosis and treatment considerations

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