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2007 OMIG, Abstract 10

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A Fluoroquinolone (FQ)-resistant Staphylococcus aureus Rabbit Endophthalmitis Model  Demonstrates a Topical 4th Generation FQ Provides More Effective Prophylaxis Than a 3rd Generation FQ.
E. G. Romanowski1, R. P. Kowalski1, F. S. Mah1, K. A. Yates1, H. Sasaki2, M. Fukuda2, Y. J. Gordon11The Charles T. Campbell Ophthalmic Microbiology Laboratory, UPMC Eye Center, University of Pittsburgh, Pittsburgh, PA., 2Department of Ophthalmology, Division of Sensory Organ Medicine, Kanazawa Medical University, Kahoku, Ishikawa, Japan.

Purpose: Controversy surrounds the clinical advantage of a 4th generation fluoroquinolone (FQ) over a 3rd generation. The aim of this study was to determine whether moxifloxacin was more effective than levofloxacin in preventing FQ-resistant Staphylococcus aureus endophthalmitis in an established rabbit model.
Methods: Three regimens of topical treatments (moxifloxacin 0.5% [Alcon Laboratories, Ft. Worth, TX], levofloxacin 0.5% [Santen Pharmaceutical Co. Ltd. Osaka, Japan], and saline) were tested as prophylaxis to prevent endophthalmitis. For each treatment regimen, drops were instilled every 15 minutes for one hour (5 drops) into the left eyes of 15 rabbits. After appropriate anesthesia, the aqueous was injected with 2 x 104 colony forming units ofFQ-resistant S. aureus (moxifloxacin MIC = 4 µg/ml, levofloxacin MIC > 32 µg/ml) commonly seen in our clinic with presentation of S. aureus endophthalmitis. One drop of each treatment of topical was applied immediately after injection followed by 4 additional applications over 24 hours. At 24 hours post injection, the eyes were graded  for clinical signs of endophthalmitis (ocular discharge, conjunctivitis/scleral injection, limbal injection, hypopyon, iritis, anterior chamber cells, anterior chamber flare, corneal infiltration, and fibrin production) using a severity scale (0 to 3). The aqueous and vitreous were tapped for bacterial colony counts. The data were analyzed using the Mood Median and the Fisher’s Exact tests.
Results: Topical moxifloxacin 0.5% significantly (p= 0.0001) prevented the clinical presentation of endophthalmitis in more rabbits (12/15, 80%) than levofloxacin 0.5% (2/15, 13%) and saline (2/15, 13%). The Total Median Clinical Score for the moxifloxacin group (1.0) was significantly (p= 0.0004) lower than the levofloxacin (20.0) and saline (23.0) groups. Culture-negative eyes (aqueous or vitreous) were less frequent in the levofloxacin (8/15, 53%) and saline (1/15, 7%) groups than the moxifloxacin group (12/15, 80%).
Conclusions: Moxifloxacin, a 4th generation FQ, was more effective in preventing endophthalmitis due to FQ-resistant S. aureus, than levofloxacin, a 3rd generation FQ. This in vivo study supports the “proof-of-principle” that a 4th generation FQ may be more potent than a 3rd generation FQ in preventing experimental endophthalmitis.

Support: Alcon Laboratories.                        Disclosure code: F, C



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