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      Treatment-Resistant Bacterial Keratitis: Challenges and Solutions

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          Abstract

          Bacterial keratitis is an important ophthalmic emergency and one of the most common causes of corneal blindness. The main causes of treatment resistance in bacterial keratitis are failure to eliminate predisposing factors, misdiagnosis and mistreatment. At first, exogenous, local and systemic predisposing factors that disturbing ocular surface must be eliminated to improve corneal ulcers and to prevent recurrences. Smears and scrapings for staining and culture are indispensable diagnostic tools for cases of sight-threatening keratitis (centrally located, multifocal, characterized by melting, painful). Main treatment agents in bacterial keratitis treatment are topical antibiotics. Until the results of culture antibiograms reach the ophthalmologist, empirical antibiotic selections based on direct microscopic examination and gram stain findings are the most appropriate initial treatment approach currently. S. aureus and coagulase-negative staphylococci (CoNS), the most common gram-positive agents, have resistance rates of more than 30% for fluoroquinolone and methicillin. Multidrug resistance rates are similarly high in these microorganisms. P. aeruginosa is the most common gram-negative micro-organism, in case of multidrug-resistant isolates, both functional and anatomical prognosis of the eyes are very poor. In cases of sight-threatening and resistant keratitis, antibiotic susceptibility testing containing imipenem, colistin, and linezolid is seeming to be an important requirement. Despite its efficiency limited to superficial cases, a nonpharmaceutical anti-infective treatment option such as corneal crosslinking for bacterial keratitis is an emerging hope, while antibiotic resistance increases.

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          Increased resistance of crosslinked cornea against enzymatic digestion.

          Collagen-crosslinking using combined riboflavin/ UVA treatment has been developed by us as a new treatment for keratoconus by stiffening the collagenous matrix. Recently, we have started to use the same method for the treatment of corneal ulcers. The aim of the present study was to evaluate the influence of the crosslinking treatment on the resistance of the cornea against enzymatic degradation. 60 enucleated porcine eyes were treated with the photosensitizer riboflavin and UVA-irradiation (370 nm; irradiance of 1, 2 or 3 mW/cm2) for 30 minutes and compared with 20 untreated control eyes. After crosslinking treatment, the corneal buttons were trephined and exposed to pepsin, trypsin and collagenase solutions. The extent of the corneal digestion was monitored daily. Selected cases were examined by light microscopy. The corneal buttons crosslinked with riboflavin/ UVA at 3 mW/cm2 were dissolved only by day 13 following pepsin digestion and by day 14 following collagenase treatment versus 6 days in the untreated control corneas. Digestion by trypsin was observed on day 5 in buttons crosslinked at 3 mW/cm2 compared to day 2 in the control corneas. Microscopically, a prolonged preservation especially of the anterior portion of the crosslinked corneas could be demonstrated. Photochemical crosslinking of the cornea using riboflavin and UVA results in a markedly increased resistance versus collagen digesting enzymes. The findings support the use of the new method in the treatment of corneal ulcers.
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            The Persistent Dilemma of Microbial Keratitis: Global Burden, Diagnosis, and Antimicrobial Resistance

            Microbial keratitis is a potentially blinding condition that must be treated emergently to preserve vision. Although long recognized as a significant cause of corneal blindness, our understanding of its true global scale, associated burden of disease, and etiological patterns remains somewhat limited. Current epidemiological data suggest that microbial keratitis may be epidemic in parts of the world-particularly within South, South-East, and East Asia-and may exceed 2 million cases per year worldwide. Etiological patterns vary between economically developed and developing countries, with bacterial predominance in the former and fungal predominance in the latter. The key to effective management lies in timely diagnosis; however, the current gold standard of stain and culture remains time consuming and often yields no clinically useful results. For this reason, there are attempts to develop highly sensitive and accurate molecular diagnostic tools to provide rapid diagnosis, inform treatment decision making, and minimize the threat of antimicrobial resistance. We provide an overview of these key areas and of avenues for further research toward the goal of more effectively addressing the problem of microbial keratitis on both an individual and public health level.
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              Core elements of hospital antibiotic stewardship programs from the Centers for Disease Control and Prevention.

              The proven benefits of antibiotic stewardship programs (ASPs) for optimizing antibiotic use and minimizing adverse events, such as Clostridium difficile and antibiotic resistance, have prompted the Centers for Disease Control and Prevention (CDC) to recommend that all hospitals have an ASP. This article summarizes Core Elements of Hospital Antibiotic Stewardship Programs, a recently released CDC document focused on defining the infrastructure and practices of coordinated multidisciplinary programs to improve antibiotic use and patient care in US hospitals.
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                Author and article information

                Journal
                Clin Ophthalmol
                Clin Ophthalmol
                OPTH
                clinop
                Clinical Ophthalmology (Auckland, N.Z.)
                Dove
                1177-5467
                1177-5483
                29 January 2020
                2020
                : 14
                : 287-297
                Affiliations
                [1 ]Private Office , Izmir, Turkey
                [2 ]Adiyaman University, Training and Research Hospital , Adiyaman, Turkey
                Author notes
                Correspondence: Sait Egrilmez Private Office , 1593/1 Sok. No: 4 B Blok D: 41 Mansuroglu Mah, Bayrakli, Izmir35535, TurkeyTel +90 505 4504765 Email saitegrilmez@gmail.com
                Author information
                http://orcid.org/0000-0002-6971-527X
                http://orcid.org/0000-0003-1473-9001
                Article
                181997
                10.2147/OPTH.S181997
                6996220
                32099313
                eaba772e-348e-40cd-9131-9c806402e7b5
                © 2020 Egrilmez and Yildirim-Theveny.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 16 August 2019
                : 10 December 2019
                Page count
                Tables: 2, References: 69, Pages: 11
                Categories
                Review

                Ophthalmology & Optometry
                bacterial keratitis,antibiotic resistance,multidrug resistant,corneal crosslinking

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