<p>Treatment-Resistant Bacterial Keratitis: Challenges and Solutions</p>

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.

Morphological and cytokine profiles as key parameters to distinguish between Gram-negative and Gram-positive bacterial keratitis

“…In our Gram+ve cohort like other studies, a high number of coagulase-negative staphylococcal species (CNS) 53 – 55 , majority of which are S. epidermidis 4 . CNS represent over 80 different species and are regular isolates worldwide 53 , 54 and are increasingly found to be responsible for infections and disease pathogenesis 53 . Similarly, our regional laboratory has shown that the majority of the CNS isolates are S. epidermidis 4 .…”

Staphylococcus aureus Keratitis: Incidence, Pathophysiology, Risk Factors and Novel Strategies for Treatment

“…The Royal College of Ophthalmologists recommends that treatment of keratitis should begin with a broad spectrum antibiotic as empirical therapy [ 32 ], even before the culture and sensitivity results have returned [ 41 ]. Antibiotic therapy is usually topical monotherapy [ 50 ]. Fluoroquinolones are a commonly used group of antibiotics for empirical therapy in ophthalmology [ 51 ]; these include ciprofloxacin, moxifloxacin, levofloxacin and ofloxacin [ 32 ].…”

“…Response to treatment is evaluated within the first couple of days, and the treatment course is modified according to the culture results. For cases of multi-drug resistant Gram-positive bacterial keratitis such as MRSA, vancomycin is regarded as the best option [ 50 ]. Since the first case in 2002, there have been only 52 cases of vancomycin-resistant S. aureus reported worldwide [ 53 ].…”

“…Since the first case in 2002, there have been only 52 cases of vancomycin-resistant S. aureus reported worldwide [ 53 ]. Linezolid is another potential option for targeting multi-drug resistant Gram-positive bacteria in individuals with vancomycin intolerance [ 50 ]. In cases of unresponsive treatment, corneal rupture or recurrent keratitis, a corneal graft may be required.…”

“…Other factors such as tear dilution can also prevent optimal concentrations from reaching the targeted area [ 63 ], and systemic side effects can result due to drainage of the drug into the lacrimal system [ 64 ]. Initial management of bacterial keratitis usually requires hourly drop instillation of antibiotics, which can be challenging to follow and a burden to patients [ 50 ]. An area of research for novel therapies concern methods that improve drug delivery to the ocular surface and consequently improve the performance of the antibiotic.…”