Article

Mycotic keratitis: Epidemiology, diagnosis and management

Department of Ocular Microbiology, Institute of Ophthalmology, Joseph Eye Hospital, Tiruchirapalli, India.
Clinical Microbiology and Infection (Impact Factor: 5.77). 01/2013; 19(3). DOI: 10.1111/1469-0691.12126
Source: PubMed

ABSTRACT

Mycotic keratitis (an infection of the cornea) is an important ocular infection, especially in young male outdoor workers. There are two frequent presentations: keratitis due to filamentous fungi (Fusarium, Aspergillus, phaeohyphomycetes and Scedosporium apiospermum are frequent causes) and keratitis due to yeast-like fungi (Candida albicans and other Candida species). In the former, trauma is usually the sole predisposing factor, although previous use of corticosteroids and contact lens wear are gaining importance as risk factors; in the latter, there is usually some systemic or local (ocular) defect. The clinical presentation and clinical features may suggest a diagnosis of mycotic keratitis; increasingly, in vivo (non-invasive) imaging techniques (confocal microscopy and anterior segment optical coherence tomography) are also being used for diagnosis. However, microbiological investigations, particularly direct microscopic examination and culture of corneal scrape or biopsy material, still form the cornerstone of diagnosis. In recent years, the PCR has gained prominence as a diagnostic aid for mycotic keratitis, being used to complement microbiological methods; more importantly, this molecular method permits rapid specific identification of the aetiological agent. Although various antifungal compounds have been used for therapy, management of this condition (particularly if deep lesions occur) continues to be problematic; topical natamycin and, increasingly, voriconazole (given by various routes) are key therapeutic agents. Therapeutic surgery, such as therapeutic penetrating keratoplasty, is needed when medical therapy fails. Increased awareness of the importance of this condition is likely to spur future research initiatives.

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    • "It possesses activity against a great variety of yeast and filamentous fungal pathogens, inc l u di ng A l t e r n a r i a , C an d i da , C e ph a l o s p or i u m, Colletotrichum, Curvularia, Lasiodiplodia, Scedosporium, Trichophyton and Penicillium spp. (Kaliamurthy et al. 2004; Thomas and Kaliamurthy 2013; Hsiao et al. 2014), and is currently considered the most effective medication against Fusarium and Aspergillus (Lalitha et al. 2007). Additionally, PIM is also effective for the treatment of keratitis produced by protozoa such as Acanthamoeba (Sunada et al. 2014). "
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    ABSTRACT: Pimaricin (natamycin) is a small polyene macrolide antibiotic used worldwide. This efficient antimycotic and antiprotozoal agent, produced by several soil bacterial species of the genus Streptomyces, has found application in human therapy, in the food and beverage industries and as pesticide. It displays a broad spectrum of activity, targeting ergosterol but bearing a particular mode of action different to other polyene macrolides. The biosynthesis of this only antifungal agent with a GRAS status has been thoroughly studied, which has permitted the manipulation of producers to engineer the biosynthetic gene clusters in order to generate several analogues. Regulation of its production has been largely unveiled, constituting a model for other polyenes and setting the leads for optimizing the production of these valuable compounds. This review describes and discusses the molecular genetics, uses, mode of action, analogue generation, regulation and strategies for increasing pimaricin production yields.
    Full-text · Article · Oct 2015 · Applied Microbiology and Biotechnology
    • "However, these treatments also increase the susceptibility of the patients to various fungal infections [1] [2] [3]. Long-term topical or systemic uses of corticosteroids are among the predisposing factors for ophthalmic mycoses like fungal endophthalmitis [4] and mycotic keratitis [5] [6]. These steroids also stimulate growth, epithelial adhesion [2] [7], germination and secretion of extracellular aspartic proteases as well as phospholipases [8] of the opportunistic human pathogen Candida albicans. "
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    ABSTRACT: The fluorinated glucocorticoid betamethasone stimulated both the extracellular phospholipase production and hypha formation of the opportunistic human pathogen Candida albicans and also decreased the efficiency of the polyene antimycotics amphotericin B and nystatin against C. albicans in a dose-dependent manner. Importantly, betamethasone increased synergistically the anti-Candida activity of the oxidative stress generating agent menadione, which may be exploited in future combination therapies to prevent or cure C. albicans infections, in the field of dermatology. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    No preview · Article · Feb 2015 · Journal of Basic Microbiology
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    • "It is important to identify the pathogen of keratitis [1,2]. The most common pathogens of fungal keratitis are Candida albicans and Fusarium species [2], although the prevalent species differ in different geographical areas of the world [1]. Trichophyton is a wide distributed species of dermatophyte and a common pathogen of tinea capitis, flavus, and onychomycosis in dermatologic area [3,4], even though Trichophyton keratitis is not common [5,6]. "
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    ABSTRACT: Background Fungal keratitis is difficult to treat that can result in corneal blindness requiring penetrating keratoplasty and in fungal endothalmitis. We report a case of fungal keratitis and onychomycosis simultaneously infected by Trichophyton. Case presentation A 77-year old male presented with ocular pain, conjunctival injection, and severe loss of vision in his left eye. His best corrected visual acuity was hand movements in the left eye, and slit-lamp examination showed a corneal ulcer with feathery margin and hypopyon. Bacterial and fungal smear/culture showed no organism, and there was no improvement in spite of treatment with topical fortified 5% cefazolin and 2% tobramycin. Trichophyton species was identified by repeated cultures. We found onychomycosis on the patient’s foot, where the same fungal species were identified. Regimen was changed to topical itraconazole and systemic intravenous itraconazole. No clinical improvement was observed, so therapeutic penetrating keratoplasty and cryotherapy was done with continuation of antifungal therapy. The graft was clear at postoperative 1 month and no evidence of recurrence was found. Conclusion It is important to identify the pathogen of keratitis because early identification of pathogen causing keratitis provides the appropriate treatment in early phase of keratitis. It is necessary to search for other fungal skin infections such as onychomycosis and athelete’s foot considering the fungal keratitis following skin infection. In addition, fungal skin infection including onychomycosis should be treated for prevention of fungal keratitis as soon as possible.
    Full-text · Article · Jul 2014 · BMC Ophthalmology
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Questions & Answers about this publication

  • Matthew John Kneale added an answer in Cornea:
    Current role of Oral anti-fungal agents in fungal keratitis - can anyone help?
    Is there any extra advantage of prescribing oral anti-fungal agents in addition to topical anti-fungal drops in patients of fungal keratitis? If yes, then what is the indication, what is the best agent for this purpose and the correct dosing and duration?
    Matthew John Kneale
    A meta-analysis of nine randomised, controlled trials (568 patients) concluded there is little evidence to suggest a particular oral antifungal over topical antifungals, and vice versa. (Florcurz & Peczon, 2012: Medical interventions for fungal
    keratitis. Cochrane Database Syst Rev 2012)

    If there are laboratories near you which perform antifungal susceptibility testing, this may be worthwhile in order to choose the best therapeutic regimen.

    Thomas & Kaliamurthy (2013) suggest that the following agents are suitable for fungal keratitis:

    Topical: natamycin (5%), econazole (1%), AmB (0.15-0.3%), 5FC (1%) clotrimazole (1%), miconazole (1%), ketoconazole (1-2%), itraconazole (1%), fluconazole (1%), voriconazole (1-2%), and caspofungin (0.5%).

    IV: Amphotericin and miconazole (600-1200mg/day)

    Oral: ketoconazole (beware side effects, check FDA info; 200-600mg/day), itraconazole (100-200mg/day), fluconazole (50-200mg/day) or voriconazole (400mg/day).

    Other options include intrastromal injections of voriconazole and AmB, itracameral voriconazole, or intravitreal AmB, fluconazole and voriconazole.

    All options are discussed in more detail in that review.
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      [Show abstract] [Hide abstract]
      ABSTRACT: Mycotic keratitis (an infection of the cornea) is an important ocular infection, especially in young male outdoor workers. There are two frequent presentations: keratitis due to filamentous fungi (Fusarium, Aspergillus, phaeohyphomycetes and Scedosporium apiospermum are frequent causes) and keratitis due to yeast-like fungi (Candida albicans and other Candida species). In the former, trauma is usually the sole predisposing factor, although previous use of corticosteroids and contact lens wear are gaining importance as risk factors; in the latter, there is usually some systemic or local (ocular) defect. The clinical presentation and clinical features may suggest a diagnosis of mycotic keratitis; increasingly, in vivo (non-invasive) imaging techniques (confocal microscopy and anterior segment optical coherence tomography) are also being used for diagnosis. However, microbiological investigations, particularly direct microscopic examination and culture of corneal scrape or biopsy material, still form the cornerstone of diagnosis. In recent years, the PCR has gained prominence as a diagnostic aid for mycotic keratitis, being used to complement microbiological methods; more importantly, this molecular method permits rapid specific identification of the aetiological agent. Although various antifungal compounds have been used for therapy, management of this condition (particularly if deep lesions occur) continues to be problematic; topical natamycin and, increasingly, voriconazole (given by various routes) are key therapeutic agents. Therapeutic surgery, such as therapeutic penetrating keratoplasty, is needed when medical therapy fails. Increased awareness of the importance of this condition is likely to spur future research initiatives.
      Full-text · Article · Jan 2013 · Clinical Microbiology and Infection