Romanowski Eric G, Mah Francis S, Yates Kathleen A, Kowalski Regis P, Gordon Y Jerold
Charles T. Campbell Ophthalmic Microbiology Laboratory, UPMC Eye Center, The Eye and Ear Institute, Department of Ophthalmology, University of Pittsburgh School of Medicine, 203 Lothrop Street, Pittsburgh, PA 15213, USA.
Am J Ophthalmol. 2005 May;139(5):867-77. doi: 10.1016/j.ajo.2005.01.021.
To determine whether gatifloxacin-resistant S. aureus (Gat-R-Sa) keratitis could be successfully treated with topical Zymar (gatifloxacin 0.3%) in a rabbit model.
Experimental animal study.
Two separate studies were performed each using two clinical isolates of Gat-R-Sa, with MICs of 12 and 64 mug/ml to gatifloxacin. Study 1 consisted of four treatment groups (Zymar, Quixin [levofloxacin 0.5%], Ciloxan [ciprofloxacin 0.3%], and saline). Study 2 consisted of Zymar, cefazolin 50 mg/ml, vancomycin 50 mg/ml, and saline. Rabbits were infected intrastromally with 2,000 cfu in both eyes. Topical therapy began after four hours, every 15 minutes for 5 hours. After therapy, the eyes were graded for clinical signs of infection (blepharitis, conjunctivitis, iritis, corneal edema, and corneal infiltrates), and the corneas were homogenized to determine viable bacterial counts.
Study 1: for both isolates, Zymar-treated eyes demonstrated significantly lower clinical scores compared with Ciloxan and saline, and significantly decreased the number of viable bacteria recovered compared with all groups. Study 2: for both isolates, Zymar and cefazolin demonstrated significantly lower clinical scores compared with vancomycin and saline. Zymar, cefazolin, and vancomycin significantly decreased the number of viable bacteria recovered compared with the saline control.
We demonstrated the "Proof of Principle" that in vitro antibiotic resistance, based on CLSI standards, does not always correlate with in vivo treatment failure in the eye. An aggressive treatment regimen with Zymar appears to overcome in vitro resistance, resulting in the successful treatment of Gat-R-Sa infections in the NZW rabbit keratitis model.
在兔模型中确定局部使用泽马克（加替沙星0.3%）能否成功治疗耐加替沙星金黄色葡萄球菌（Gat-R-Sa）角膜炎。
实验动物研究。
进行了两项独立研究，每项研究使用两株Gat-R-Sa临床分离株，其对加替沙星的最低抑菌浓度分别为12和64μg/ml。研究1包括四个治疗组（泽马克、喹诺仙[左氧氟沙星0.5%]、西洛欣[环丙沙星0.3%]和生理盐水）。研究2包括泽马克、头孢唑林50mg/ml、万古霉素50mg/ml和生理盐水。双眼基质内接种2000cfu使兔感染。4小时后开始局部治疗，每15分钟一次，共5小时。治疗后，对眼睛进行感染临床体征分级（睑缘炎、结膜炎、虹膜炎、角膜水肿和角膜浸润），并将角膜匀浆以确定活菌计数。
研究1：对于两株分离株，与西洛欣和生理盐水相比，用泽马克治疗的眼睛临床评分显著更低，与所有组相比，回收的活菌数量显著减少。研究2：对于两株分离株，与万古霉素和生理盐水相比，泽马克和头孢唑林的临床评分显著更低。与生理盐水对照组相比，泽马克、头孢唑林和万古霉素显著减少了回收的活菌数量。
我们证明了“原理验证”，即基于CLSI标准的体外抗生素耐药性并不总是与眼部体内治疗失败相关。积极的泽马克治疗方案似乎能克服体外耐药性，从而在新西兰白兔角膜炎模型中成功治疗Gat-R-Sa感染。
