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Eric Romanowski, Kathleen Yates, Katherine O'Connor, Francis Mah, Leela Raju, Robert Shanks, Regis Kowalski; The Comparison of Topical RPX-978 (an Ophthalmic Formulation of Tigecycline) to Topical Vancomycin in a MRSA Rabbit Keratitis Model. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4293.
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Tigecycline is a glycylcycline antibiotic indicated for the IV treatment of systemic infections. RPX-978 (RPX) is a topical ophthalmic formulation of tigecycline in development for the treatment of ocular infections. The efficacy of RPX was compared to topical vancomycin (VAN) using a methicillin-resistant Staphylococcus aureus (MRSA) keratitis model.
In 32 NZW rabbits, corneal epithelial defects were created in the left eyes using an Amoils epithelial scrubber (abraded corneas), while the epithelia of the right corneas remained intact (intact corneas) to determine if corneal abrasion affected drug efficacy by enhancing penetration. The corneas were intrastromally injected with 1000 CFU of MRSA. Rabbits were separated into 4 groups (n=8): A) RPX (0.5% tigecycline), B) VAN 5%, C) normal saline (SAL), and D) no treatment (euthanized before treatment for baseline CFU). 4h after MRSA challenge, the topical treatment regimen of one drop every 15 minutes for 5h was initiated. After treatment, all eyes were slit lamp examined for presentations of infection. The eyes were graded using a 0-3 severity scale. After examination and 1h after treatment, the animals were euthanized and the corneas were harvested for CFU determination. The data were non-parametrically analyzed.
The total clinical scores for RPX treatment were less than SAL which was less than VAN (p<0.05, Kruskal-Wallis) in both abraded and intact corneas. This indicated that clinical pathology from infection and drug toxicity was less for RPX. VAN and RPX produced similar reductions in CFU, and both were less than SAL (P<0.05, K-W) in both abraded and intact corneas. Both treatments demonstrated a 99.9% reduction in comparison to baseline CFU (P<0.05, K-W) in both intact and abraded corneas. The comparable reduction in CFU of abraded and intact corneas (P>0.05, Mann Whitney) by RPX suggest high penetration through the corneal epithelium. For RPX and VAN, the CFU of abraded and intact corneas were statistically equivalent suggesting that RPX penetrated through the corneal epithelium as well as VAN.
RPX was equally efficacious as fortified VAN in this MRSA keratitis model. Additional studies are warranted to determine the potential of RPX in the treatment of ocular infections due to other bacteria.
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