Introduction Topical antiinfective prophylaxis has become the standard of care for ophthalmic surgery, and the fluoroquinolones (FQs) have been the predominant off-label choice. Ciprofloxacin (Ciloxan, Alcon Laboratories, Ft. Worth, TX, USA) and ofloxacin (Ocuflox, Allergan, Irvine, CA, USA) were the initial second-generation FQs to be used for topical surgical prophylaxis. This was followed by the third-genera- tion FQ, levofloxacin (Quixin and Cravit, USA/Japan). More recently, the fourth-generation FQs, moxifloxacin (Vigamox and Vegamox, Alcon Laboratories, USA/Japan; Vegamox is the Japanese product and has the same formu- lation as Vigamox in the United States) and gatifloxacin (Zymar, Allergan), have been introduced as an improve- ment to provide better topical surgical prophylaxis. Contro- versy surrounds the clinical advantages of a fourth-generation FQ over a third-generation FQ. Studies in the ophthalmic literature support the advantages of a fourth-generation Jpn J Ophthalmol 2008;52:211–216 DOI 10.1007/s10384-008-0530-1 © Japanese Ophthalmological Society 2008 LABORATORY INVESTIGATION A Comparison of Moxifloxacin and Levofloxacin Topical Prophylaxis in a Fluoroquinolone-Resistant Staphylococcus aureus Rabbit Model Regis P. Kowalski 1 , Eric G. Romanowski 1 , Francis S. Mah 1 , Hiroshi Sasaki 2 , Masamichi Fukuda 2 , and Y. J. Gordon 1 1 The Charles T. Campbell Ophthalmic Microbiology Laboratory, The University of Pittsburgh Medical Center, Pittsburgh, PA, USA, and the UPMC Eye Center, Ophthalmology and Visual Science Research Center, Eye and Ear Institute, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; 2 Department of Ophthalmology Division of Sensory Organ Medicine, Kanazawa Medical University, Ishikawa, Kanazawa, Japan Abstract Purpose: Moxifloxacin, a fourth-generation fluoroquinolone (FQ), was compared to levofloxacin, a third- generation FQ, for preventing FQ-resistant, methicillin-resistant Staphylococcus aureus (FQrMRSA) endophthalmitis in a rabbit model. Methods: Three regimens of topical treatments (moxifloxacin 0.5%, levofloxacin 0.5%, and saline) were tested to prevent endophthalmitis. For each regimen, drops were instilled every 15 min for 1 h into the left eyes of 15 rabbits. After anesthesia, 2 × 10 4 cfu of FQrMRSA was injected into the aqueous. One drop of treatment was given immediately, and another four drops were applied over 24 h. At 24 h, the eyes were clinically graded for endophthalmitis. After the rabbits were sacrificed, the aqueous and vitre- ous were tapped for bacterial colony counts. Results: Topical moxifloxacin (12/15, 80%) significantly (P = 0.0001) prevented clinical endophthalmitis in more rabbits than levofloxacin (2/15, 13%) or saline (2/15, 13%). The total median clinical score for moxifloxacin treatment (1.0) was significantly (P = 0.0004) lower than that for levofloxacin (20.0) or saline (23.0). Culture-negative eyes were less frequent for levofloxacin (8/15, 53%) and saline (1/15, 7%) treatments than for moxifloxacin treatment (12/15, 80%). Conclusion: This in vivo study indicates that moxifloxacin, a fourth-generation FQ, may be more effective than levofloxacin, a third-generation FQ, in preventing experimental FQrMRSA. endophthalmitis. Jpn J Ophthalmol 2008;52:211–216 © Japanese Ophthalmological Society 2008 Key Words: endophthalmitis, levofloxacin, moxifloxacin, rabbit model, Staphylococcus aureus Received: November 16, 2007 / Accepted: March 6, 2008 Correspondence and reprint requests to: Regis P. Kowalski, The Eye and Ear Institute Bldg., Ophthalmic Microbiology, Room 642, 203 Lothrop Street, Pittsburgh, PA 15213, USA e-mail: kowalskirp@upmc.edu