两种喹诺酮类滴眼液治疗细菌性角膜炎的动物实验与临床试验观察

Effect of Two Quinolone Antibiotics Eye Drops on Bacterial Keratitis in Rabbits and Patients

目的:比较喹诺酮类抗菌药加替沙星和左氧氟沙星滴眼液治疗细菌性角膜炎的疗效。方法:动物实验:建立兔细菌性角膜炎模型,随机分为接种菌基线组、空白对照组、0.5%左氧氟沙星组、0.3%加替沙星组。按预定给药方案给药,观察兔角膜炎情况,同时进行房水细菌培养,评价细菌学变化。临床试验:44例患者随机分为加替沙星组和左氧氟沙星组,观察用药后疗效。结果:加替沙星和左氧氟沙星对金葡菌的MIC分别为0.062 5 mg·L^(-1)和0.125 mg·L^(-1),加替沙星组的角膜菌落计数为1.68±0.36,显著低于左氧氟沙星组的3.73±0.39(P<0.01);症状体征总评分加替沙星明显低于左氧氟沙星(3.21±1.44vs 6.92±3.88,P<0.01);临床治疗中加替沙星和左氧氟沙星的有效率分别为95.45%和86.36%,但差异无统计学意义(P>0.05)。结论:菌落计数、症状体征评分显示加替沙星优于左氧氟沙星,提示加替沙星相对于左氧氟沙星而言,在眼局部给药用于治疗金葡菌性角膜炎方面具有一定的优势。在临床试验中,两组疗效差异无显著性意义。

Objective： To evaluate the therapeutic effectiveness of gatifloxacin and levofloxacin eye drops on bacterial keratitis in both rabbits and patients. Method： Rabbit corneas were injected with approximately 100 colony- forming units （CFU） of S. aureus ATCC25923. Nine hours later, the rabbits were divided into four groups randomly： bacteria vaccination group, control group, levoflox- acin eye drops （0.5 % ） group and gatifloxacin eye drops （0.3 % ） group. The eyes were examined and aqueous was harvested after the last administration. The number of bacteria in the corneas before and after the treatment was compared. Totally 44 patients were divided into two groups randomly, and the therapeutic efficacy was also observed. Result： The MIC for gatifloxacin and levofloxacin against the S. aureus ATCC25923 was 0. 062 5 mg ~ L-1 and 0.125 mg~ L-1, respectively. The gatifloxacin group had significantly lower CFU than levofloxacin group （ 1.68 ＋ 0.36 and 3.73 -＋ 0.39, respectively, P 〈 0.01 ）. Symptom score of gatifloxacin group was obviously lower than that of levofloxacin group （ 3.21 ＋ 1.44 and 6.92 ＋ 3.88, respectively, P 〈 0.01 ）. In the patients, the therapy efficiency of gatifloxacin and levofloxacin group was 95.45% and 86.360%, respectively without significant difference. Conclusion： Gatifloxacin shows significant advantages in CFU and symptom scores compared with levofloxacin. For bacterial keratitis, gatifloxacin has some ad- vantages compared with lew^floxacin. In patients, although the therapy efficiency of gatifloxacin is better than levofloxacin, there is no statistical significance.