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John Eric Romanowski, Eric G Romanowski, Kathleen A Yates, Regis P Kowalski; The Successful Treatment of Experimental Methicillin-Resistant Staphylococcus aureus (MRSA) Keratitis with a Topical β-Lactam Antibiotic. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3658.
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The systemic treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections with β-lactam (β-L) antibiotics is contraindicated due to resistance of the bacteria. However, it is unknown if this resistance can be overcome by an excessive amount of drug delivered directly to the site of infection. The goal of the current study was to determine a “Proof of Principle” whether a topical β-lactam antibiotic (i.e. penicillin), in a high concentration, can overcome resistance and successfully treat an MRSA corneal infection using a rabbit keratitis model.
The corneas of both eyes of 32 rabbits were intrastromally infected with 2000 CFU of MRSA strain K950. The corneal epithelium was removed in the left eyes to mimic corneal ulceration while the epithelium remained in the right eyes. After 4 hours, 8 rabbits were euthanized to determine amounts of corneal bacteria at the onset of treatment. The remaining rabbits were divided into 3 treatment groups (n=8): 1) β-lactam antibiotic (6% penicillin) (β-L); 2) 2.5% vancomycin (VAN); 3) saline (SAL). The rabbits were treated topically in both eyes every 15’ for 5h. One hour after treatment, the rabbits were euthanized and the amounts of corneal bacteria from the treatment groups determined and analyzed for treatment effectiveness and bactericidal effect.
β-L was more effective than VAN in reducing MRSA when the corneal epithelium was removed (P≤0.05 Kruskal-Wallis), but was only as effective as VAN when the corneal epithelium remained (P≥0.05 K-W). Both treatments reduced colony counts compared to SAL with and without epithelium (P≤0.05 K-W). β-L was bactericidal (≥99.9% decrease in median colony counts compared to the onset of treatment) in eyes with and without epithelium while VAN was only bactericidal in eyes without epithelium.
We demonstrated a “Proof of Principle” that a β-lactam antibiotic can overcome resistance to successfully treat MRSA keratitis in a rabbit model. The β-lactam antibiotic was as or more effective than the standard of care, 2.5% vancomycin, depending if the corneal epithelium was removed, which can affect drug penetration. Additional studies are warranted to determine whether β-lactam antibiotics can be used as a potential alternative treatment for MRSA keratitis.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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