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Clinical & Experimental Ophthalmology Jul 2022Globally, infectious keratitis is the fifth leading cause of blindness. The main predisposing factors include contact lens wear, ocular injury and ocular surface... (Review)
Review
Globally, infectious keratitis is the fifth leading cause of blindness. The main predisposing factors include contact lens wear, ocular injury and ocular surface disease. Staphylococcus species, Pseudomonas aeruginosa, Fusarium species, Candida species and Acanthamoeba species are the most common causal organisms. Culture of corneal scrapes is the preferred initial test to identify the culprit organism. Polymerase chain reaction (PCR) tests and in vivo confocal microscopy can complement the diagnosis. Empiric therapy is typically commenced with fluoroquinolones, or fortified antibiotics for bacterial keratitis; topical natamycin for fungal keratitis; and polyhexamethylene biguanide or chlorhexidine for acanthamoeba keratitis. Herpes simplex keratitis is mainly diagnosed clinically; however, PCR can also be used to confirm the initial diagnosis and in atypical cases. Antivirals and topical corticosteroids are indicated depending on the corneal layer infected. Vision impairment, blindness and even loss of the eye can occur with a delay in diagnosis and inappropriate antimicrobial therapy.
Topics: Acanthamoeba; Acanthamoeba Keratitis; Blindness; Corneal Ulcer; Eye Infections, Fungal; Humans
PubMed: 35610943
DOI: 10.1111/ceo.14113 -
Ophthalmology Nov 2017Infectious keratitis is a major global cause of visual impairment and blindness, often affecting marginalized populations. Proper diagnosis of the causative organism is... (Review)
Review
Infectious keratitis is a major global cause of visual impairment and blindness, often affecting marginalized populations. Proper diagnosis of the causative organism is critical, and although culture remains the prevailing diagnostic tool, newer techniques such as in vivo confocal microscopy are helpful for diagnosing fungus and Acanthamoeba. Next-generation sequencing holds the potential for early and accurate diagnosis even for organisms that are difficult to culture by conventional methods. Topical antibiotics remain the best treatment for bacterial keratitis, and a recent review found all commonly prescribed topical antibiotics to be equally effective. However, outcomes remain poor secondary to corneal melting, scarring, and perforation. Adjuvant therapies aimed at reducing the immune response associated with keratitis include topical corticosteroids. The large, randomized, controlled Steroids for Corneal Ulcers Trial found that although steroids provided no significant improvement overall, they did seem beneficial for ulcers that were central, deep or large, non-Nocardia, or classically invasive Pseudomonas aeruginosa; for patients with low baseline vision; and when started early after the initiation of antibiotics. Fungal ulcers often have worse clinical outcomes than bacterial ulcers, with no new treatments since the 1960s when topical natamycin was introduced. The randomized controlled Mycotic Ulcer Treatment Trial (MUTT) I showed a benefit of topical natamycin over topical voriconazole for fungal ulcers, particularly among those caused by Fusarium. MUTT II showed that oral voriconazole did not improve outcomes overall, although there may have been some effect among Fusarium ulcers. Given an increase in nonserious adverse events, the authors concluded that they could not recommend oral voriconazole. Viral keratitis differs from bacterial and fungal cases in that it is often recurrent and is common in developed countries. The Herpetic Eye Disease Study (HEDS) I showed a significant benefit of topical corticosteroids and oral acyclovir for stromal keratitis. HEDS II showed that oral acyclovir decreased the recurrence of any type of herpes simplex virus keratitis by approximately half. Future strategies to reduce the morbidity associated with infectious keratitis are likely to be multidimensional, with adjuvant therapies aimed at modifying the immune response to infection holding the greatest potential to improve clinical outcomes.
Topics: Anti-Bacterial Agents; Antifungal Agents; Antiviral Agents; Corneal Ulcer; Diagnostic Techniques, Ophthalmological; Eye Infections, Bacterial; Eye Infections, Fungal; Female; Glucocorticoids; Humans; Keratitis, Herpetic; Male; Randomized Controlled Trials as Topic; Visual Acuity
PubMed: 28942073
DOI: 10.1016/j.ophtha.2017.05.012 -
Clinical Microbiology and Infection :... Mar 2013Mycotic keratitis (an infection of the cornea) is an important ocular infection, especially in young male outdoor workers. There are two frequent presentations:... (Review)
Review
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.
Topics: Antifungal Agents; Clinical Laboratory Techniques; Debridement; Fungi; Humans; Immunocompromised Host; Keratitis; Mycoses; Wounds and Injuries
PubMed: 23398543
DOI: 10.1111/1469-0691.12126 -
Antibiotics (Basel, Switzerland) May 2023The use of antifungal drugs started in the 1950s with polyenes nystatin, natamycin and amphotericin B-deoxycholate (AmB). Until the present day, AmB has been considered... (Review)
Review
The use of antifungal drugs started in the 1950s with polyenes nystatin, natamycin and amphotericin B-deoxycholate (AmB). Until the present day, AmB has been considered to be a hallmark in the treatment of invasive systemic fungal infections. Nevertheless, the success and the use of AmB were associated with severe adverse effects which stimulated the development of new antifungal drugs such as azoles, pyrimidine antimetabolite, mitotic inhibitors, allylamines and echinochandins. However, all of these drugs presented one or more limitations associated with adverse reactions, administration route and more recently the development of resistance. To worsen this scenario, there has been an increase in fungal infections, especially in invasive systemic fungal infections that are particularly difficult to diagnose and treat. In 2022, the World Health Organization (WHO) published the first fungal priority pathogens list, alerting people to the increased incidence of invasive systemic fungal infections and to the associated risk of mortality/morbidity. The report also emphasized the need to rationally use existing drugs and develop new drugs. In this review, we performed an overview of the history of antifungals and their classification, mechanism of action, pharmacokinetic/pharmacodynamic (PK/PD) characteristics and clinical applications. In parallel, we also addressed the contribution of fungi biology and genetics to the development of resistance to antifungal drugs. Considering that drug effectiveness also depends on the mammalian host, we provide an overview on the roles of therapeutic drug monitoring and pharmacogenomics as means to improve the outcome, prevent/reduce antifungal toxicity and prevent the emergence of antifungal resistance. Finally, we present the new antifungals and their main characteristics.
PubMed: 37237787
DOI: 10.3390/antibiotics12050884 -
Clinical Ophthalmology (Auckland, N.Z.) 2011What is the most appropriate management of fungal keratitis?
CLINICAL QUESTION
What is the most appropriate management of fungal keratitis?
RESULTS
Traditionally, topical Natamycin is the most commonly used medication for filamentous fungi while Amphotericin B is most commonly used for yeast. Voriconazole is rapidly becoming the drug of choice for all fungal keratitis because of its wide spectrum of coverage and increased penetration into the cornea.
IMPLEMENTATION
Repeated debridement of the ulcer is recommended for the penetration of topical medications. While small, peripheral ulcers may be treated in the community, larger or central ulcers, especially if associated with signs suggestive of anterior chamber penetration should be referred to a tertiary center. Prolonged therapy for approximately four weeks is usually necessary.
PubMed: 21468333
DOI: 10.2147/OPTH.S10819 -
Advances in Therapy Aug 2023Fungal keratitis, an ocular fungal infection, is one of the leading causes of monocular blindness. Natamycin has long been considered the mainstay drug used for treating... (Review)
Review
Fungal keratitis, an ocular fungal infection, is one of the leading causes of monocular blindness. Natamycin has long been considered the mainstay drug used for treating fungal keratitis and is the only US Food and Drug Administration (USFDA)-approved drug, commercially available as a topical 5% w/v suspension. Furthermore, ocular fungal infection treatment takes a few weeks to months to recover, and the available marketed antifungal suspensions are associated with poor residence time, limited bioavailability (< 5%) and high dosing frequency as well as minor irritation and discomfort. Despite these challenges, natamycin is still the preferred drug choice for treating fungal keratitis, as it has fewer side effects and less ocular toxicity and is more effective against Fusarium species than other antifungal agents. Several novel therapeutic approaches for the topical delivery of natamycin have been reported to overcome the challenges posed by the conventional dosage forms and to improve ocular bioavailability for the efficient management of fungal keratitis. Current progress in the delivery systems uses approaches aimed at improving the corneal residence time, bioavailability and antifungal potency, thereby reducing the dose and dosing frequency of natamycin. In this review, we discuss the various strategies explored to overcome the challenges present in ocular drug delivery of natamycin and improve its bioavailability for ocular therapeutics.
Topics: Humans; Natamycin; Antifungal Agents; Keratitis; Eye Infections, Fungal; Cornea
PubMed: 37289410
DOI: 10.1007/s12325-023-02541-x -
Sheng Wu Gong Cheng Xue Bao = Chinese... Apr 2021Natamycin is a polyene macrolide antibiotics with strong and broad spectrum antifungal activity. It not only effectively inhibits the growth and reproduction of fungi,... (Review)
Review
Natamycin is a polyene macrolide antibiotics with strong and broad spectrum antifungal activity. It not only effectively inhibits the growth and reproduction of fungi, but also prevents the formation of some mycotoxins. Consequently, it has been approved for use as an antifungal food preservative in most countries, and is also widely used in agriculture and healthcare. Streptomyces natalensis and Streptomyces chatanoogensis are the main producers of natamycin. This review summarizes the biosynthesis and regulatory mechanism of natamycin, as well as the strategies for improving natamycin production. Moreover, the future perspectives on natamycin research are discussed.
Topics: Antifungal Agents; Fungi; Natamycin; Streptomyces
PubMed: 33973428
DOI: 10.13345/j.cjb.200394 -
Food Science and Biotechnology Nov 2021Natamycin is a natural antimicrobial peptide produced by the strains of . It effectively acts as an antifungal preservative on various food products like yogurt, khoa,... (Review)
Review
UNLABELLED
Natamycin is a natural antimicrobial peptide produced by the strains of . It effectively acts as an antifungal preservative on various food products like yogurt, khoa, sausages, juices, wines, etc. Additionally, it has been used as a bio preservative and is listed as generally recognized as a safe ingredient for various food applications. In this review, natamycin properties, production methods, toxicity, and application as a natural preservative in different foods are emphasized. This review also focuses on optimal condition and process control required in natamycin production. The mode of action and inhibitory effect of natamycin on yeast and molds inhibition and its formulation and dosage to preserve various food products, coating, and hurdle applications are summarized. Understanding the scientific factors in natamycin's production process, its toxicity, and its efficiency as a preservative will open its practical application in various food products.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s10068-021-00981-1.
PubMed: 34868698
DOI: 10.1007/s10068-021-00981-1 -
Transactions of the American... 2001To determine the risk factors and clinical signs of Curvularia keratitis and to evaluate the management and outcome of this corneal phaeohyphomycosis. (Review)
Review
PURPOSE
To determine the risk factors and clinical signs of Curvularia keratitis and to evaluate the management and outcome of this corneal phaeohyphomycosis.
METHODS
We reviewed clinical and laboratory records from 1970 to 1999 to identify patients treated at our institution for culture-proven Curvularia keratitis. Descriptive statistics and regression models were used to identify variables associated with the length of antifungal therapy and with visual outcome. In vitro susceptibilities were compared to the clinical results obtained with topical natamycin.
RESULTS
During the 30-year period, our laboratory isolated and identified Curvularia from 43 patients with keratitis, of whom 32 individuals were treated and followed up at our institute and whose data were analyzed. Trauma, usually with plants or dirt, was the risk factor in one half; and 69% occurred during the hot, humid summer months along the US Gulf Coast. Presenting signs varied from superficial, feathery infiltrates of the central cornea to suppurative ulceration of the peripheral cornea. A hypopyon was unusual, occurring in only 4 (12%) of the eyes but indicated a significantly (P = .01) increased risk of subsequent complications. The sensitivity of stained smears of corneal scrapings was 78%. Curvularia could be detected by a panfungal polymerase chain reaction. Fungi were detected on blood or chocolate agar at or before the time that growth occurred on Sabouraud agar or in brain-heart infusion in 83% of cases, although colonies appeared only on the fungal media from the remaining 4 sets of specimens. Curvularia was the third most prevalent filamentous fungus among our corneal isolates and the most common dematiaceous mold. Corneal isolates included C senegalensis, C lunata, C pallescens, and C prasadii. All tested isolates were inhibited by 4 micrograms/mL or less of natamycin. Topical natamycin was used for a median duration of 1 month, but a delay in diagnosis beyond 1 week doubled the average length of topical antifungal treatment (P = .005). Visual acuity improved to 20/40 or better in 25 (78%) of the eyes.
CONCLUSIONS
Curvularia keratitis typically presented as superficial feathery infiltration, rarely with visible pigmentation, that gradually became focally suppurative. Smears of corneal scrapings often disclosed hyphae, and culture media showed dematiaceous fungal growth within 1 week. Natamycin had excellent in vitro activity and led to clinical resolution with good vision in most patients with corneal curvulariosis. Complications requiring surgery were not common but included exophytic inflammatory fungal sequestration, treated by superficial lamellar keratectomy, and corneal perforation, managed by penetrating keratoplasty.
Topics: Adolescent; Adult; Aged; Antifungal Agents; Ascomycota; Child; Cornea; DNA, Fungal; Debridement; Eye Infections, Fungal; Female; Humans; Keratitis; Male; Middle Aged; Mycoses; Polymerase Chain Reaction; Risk Factors; Seasons
PubMed: 11797300
DOI: No ID Found -
Journal of Fungi (Basel, Switzerland) Apr 2021Mycotic or fungal keratitis (FK) is a sight-threatening disease, caused by infection of the cornea by filamentous fungi or yeasts. In tropical, low and middle-income... (Review)
Review
Mycotic or fungal keratitis (FK) is a sight-threatening disease, caused by infection of the cornea by filamentous fungi or yeasts. In tropical, low and middle-income countries, it accounts for the majority of cases of microbial keratitis (MK). Filamentous fungi, in particular spp., the aspergilli and dematiaceous fungi, are responsible for the greatest burden of disease. The predominant risk factor for filamentous fungal keratitis is trauma, typically with organic, plant-based material. In developed countries, contact lens wear and related products are frequently implicated as risk factors, and have been linked to global outbreaks of keratitis in the recent past. In 2020, the incidence of FK was estimated to be over 1 million cases per year, and there is significant geographical variation; accounting for less than 1% of cases of MK in some European countries to over 80% in parts of south and south-east Asia. The proportion of MK cases is inversely correlated to distance from the equator and there is emerging evidence that the incidence of FK may be increasing. Diagnosing FK is challenging; accurate diagnosis relies on reliable microscopy and culture, aided by adjunctive tools such as in vivo confocal microscopy or PCR. Unfortunately, these facilities are infrequently available in areas most in need. Current topical antifungals are not very effective; infections can progress despite prompt treatment. Antifungal drops are often unavailable. When available, natamycin is usually first-line treatment. However, infections may progress to perforation in ~25% of cases. Future work needs to be directed at addressing these challenges and unmet needs. This review discusses the epidemiology, clinical features, diagnosis, management and aetiology of FK.
PubMed: 33916767
DOI: 10.3390/jof7040273