Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Polo Annunziata, Messina 98168, Italy.
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Polo Annunziata, Messina 98168, Italy.
Int J Antimicrob Agents. 2016 Oct;48(4):395-400. doi: 10.1016/j.ijantimicag.2016.06.026. Epub 2016 Aug 11.
In recent years, the emergence of methicillin-resistant Staphylococcus aureus (MRSA) strains has been observed in ocular infections. Resistance of MRSA to second- and third-generation fluoroquinolones has increased interest in the fourth-generation fluoroquinolones. In this study, the antibacterial activity of gemifloxacin against MRSA ocular isolates in vitro and in a modified ex vivo rabbit keratitis model was investigated. In vitro susceptibility test results indicated that the minimum inhibitory concentrations (MICs) of gemifloxacin were lower than the MICs of other fluoroquinolones, including moxifloxacin (MIC50 range, 0.016-0.032 µg/mL; MIC90 range, 0.047-0.094 µg/mL). Results from the ex vivo keratitis model showed a statistically significant decrease in MRSA counts (0.5-2 log10 CFU/g; P <0.05) in corneas treated with 0.3% gemifloxacin every 30 min for 7 h. Moreover, the dose-response effect of different concentrations of gemifloxacin (3-3000 µg/mL) demonstrated that a dose of 30 µg/mL had the same efficacy as the highest dose of 3000 µg/mL against all S. aureus strains. Possibly, gemifloxacin reached a steady-state level in the cornea, as the fourth-generation fluoroquinolones have better anterior chamber penetration. This study demonstrated that 0.3% gemifloxacin ophthalmic solution may be an effective topical therapy for the treatment of MRSA keratitis. In addition, this reproducible, ethical and economic ex vivo infection model can be used as a mechanistically-based alternative to in vivo animal testing, bridging the gap between in vitro and in vivo results.
近年来，耐甲氧西林金黄色葡萄球菌（MRSA）菌株已在眼部感染中出现。MRSA 对第二代和第三代氟喹诺酮类药物的耐药性增加了对第四代氟喹诺酮类药物的兴趣。在这项研究中，研究了加替沙星对体外和改良兔角膜炎模型中 MRSA 眼部分离株的抗菌活性。体外药敏试验结果表明，加替沙星的最低抑菌浓度（MICs）低于其他氟喹诺酮类药物，包括莫西沙星（MIC50 范围，0.016-0.032 μg/ml；MIC90 范围，0.047-0.094 μg/ml）。体外角膜炎模型的结果表明，用 0.3%加替沙星每 30 分钟治疗 7 小时后，角膜中 MRSA 计数（0.5-2 log10 CFU/g；P <0.05）有统计学意义的下降。此外，不同浓度加替沙星（3-3000 μg/ml）的剂量反应效应表明，30 μg/ml 的剂量与 3000 μg/ml 的最高剂量对所有金黄色葡萄球菌菌株的疗效相同。可能是由于第四代氟喹诺酮类药物在前房中有更好的穿透性，加替沙星在角膜中达到了稳定状态。本研究表明，0.3%加替沙星眼用溶液可能是治疗 MRSA 角膜炎的有效局部治疗方法。此外，这种可重现、符合伦理且经济的体外感染模型可以作为体内动物试验的替代方法，在体外和体内结果之间架起桥梁。
