加替沙星治疗非结核性分枝杆菌性角膜炎的实验研究

Treatment of gatifloxacin for experimental non-tuberculous mycobacterial keratitis in rabbit

目的探讨加替沙星对兔非结核分枝杆菌(NTM)性角膜炎的治疗效果。方法利用龟分枝杆菌建立兔NTM角膜炎模型,随机分为6组,分别使用加替沙星、左氧氟沙星、环丙沙星、阿米卡星及加替沙星联合阿米卡星进行治疗,平衡盐溶液(BSS)作为对照;观察治疗前后角膜浸润面积及临床表现的变化,并对治疗1周后的角膜病灶进行细菌定量分析。结果加替沙星可抑制角膜组织内NTM的生长,使NTM角膜炎角膜浸润面积明显减小,与阿米卡星联合使用可增强其抗菌作用。结论加替沙星是治疗NTM角膜炎的有效药物之一。

Objective Non-tuberculous mycobacterial （NTM） keratitis has been recognized with increasing incidence since the initial report in 1965. Medical therapy is often unsatisfactory because of resistance of pathogen to most conventional antibiotics, The newly-developed antimicrobial agents,including gatifloxacin and moxifloxacin,have been shown to be effective in the treatment of human systemic diseases caused by NTM. This paper was to study the effectiveness of gatifloxacin against NTM keratitis in rabbit model, Methods Forty-two New Zealand white rabbits underwent unilateral lamellar keratectomy using a manual corneal trephine followed by the placement of 10000 colony-forming units （CFUs） of log-phase NTM under each flap. Eyes with NTM keratitis （seven in each group） were divided into six groups randomly and topically treated by 0.3% gatifloxacin, 0. 3% levofloxacin,0. 3% eiprofloxacin,l% amikacin and the combination of 0. 3% gatifloxacin and 1% amikacin respectively, and BSS （ balanced salt solution） was used as negative control. Topical medicine was applied eight times per day, Ocular clinical manifestation was graded and cornea infiltration area was determined before treatment and 7 days after treatment. Quantitative mycobacterium cultures were performed l week after treatment. Results The mean stromal infiltration area after treatment by gatifloxacin was （ 15.97± 2. 02） mm, and that of pretreatment was （ 18.88 ±1.99） mm,indicating that gatifloxacin inhibited the growth of NTM significantly （P 〈0.05 ）. Combined therapy of gatifloxacin and amikacin enhanced the anti-microorganism effect （ 19.69±2. 16 mm^2 in pretreatment versus 15.05 - 3.80mm^2in posttreatment,P 〈0. Ol ）. No significant differences were found in stromal infiltration area and clinical manifestation between before and after treatment of ciprofloxacin, Conclusion Gatifloxacin as well as the combination of gatifloxacin and amikacin are more effective to the treatment of NTM keratitis.