目的 探讨氟喹诺酮类抗生素加替沙星和左氧氟沙星治疗细菌性结膜炎的临床疗效和安全性.方法 采用多中心、随机、双盲、对照试验.2006年8月至2007年10月,在复旦大学附属眼耳鼻喉科医院、河南省眼科研究所、温州医学院附属视光医院、南京医科大学第一附属医院、第四军医大学西京医院、西安交通大学医学院第二附属医院6所医院进行研究.以盐酸左氧氟沙星滴眼液为有效对照,将诊断为细菌性结膜炎的235例(235只眼)患者按随机区组法分入两组:试验组118只眼,对照组117只眼,试验组滴用加替沙星,对照组滴用左氧氟沙星,每组给药方法均为每次2滴,第1-2天,每2小时滴1次,8次/d;以后每4小时滴1次,4次/d,滴入结膜囊内,疗程为7 d.所有人组患者均在试验开始前及试验结束后行结膜囊细菌培养及药物敏感试验,并在用药前和用药后第3-5天、第6-8天分别对症状、体征观察进行综合评分以及评价其安全性.采用协方差分析方法、CMH X2方法、Pearson X2检验、Fisher检验对实验数据进行统计学分析.结果 加替沙星组和左氧氟沙星组的有效率分别为94.0%(110/117只眼)和93.8%(106/113只眼),差异无统计学意义(X2=0.052,P=0.8201).加替沙星组和左氧氟沙星组的细菌清除率分别为94.1%(80/85只眼)和92.5%(74/80只眼),两组比较差异无统计学意义(P=0.3470).用药后第3～5天症状体征综合评分下降幅度加替沙星组为(4.436±2.310)分,左氧氟沙星组为(3.814±1.962)分,差异有统计学意义(F=7.280,P=0.0075).用药后第6～8天症状体征综合评分下降幅度加替沙星组为(7.487 ±2.821)分,左氧氟沙星组为(6.912±2.911)分,差异有统计学意义(F=4.060,P=0.0452).视力及局部用药后耐受性评分在两组之间无显著差异(视力F=1.04,P=0.3080;局部用药后耐受性X2=0.1372,P=0.7111).根据全部患者细菌培养结果,细菌性结膜炎致病菌以革兰阳性菌为主(共检测出革兰阳性菌20种,革兰阴性菌8种),加替沙星对革兰阳性菌的最低抑菌浓度低于左氧氟沙星(表皮葡萄球菌、金黄色葡萄球菌、凝固酶阴性葡萄球菌、甲型溶血性链球菌等).结论 加替沙星滴眼液对细菌性结膜炎有良好的治疗作用,能够有效清除致病菌,起效快,作用强,且体外抗菌活性高,不易产生耐药性,具备良好的安全性和眼部耐受性.%Objective To evaluate the different efficacy and safety to the treatment of baeterial conjunctivitis between the fluoroquinolone antibiotics gatifloxacin and levofloxacin.Methods A multicentre,random,double-blind and control trial was performed in six centers including Eye Ear Nose and Throar Hospital of Fudan University,Henan Eye Institute,Eye Hospital Affiliated to Wenzhou Medieal College,the First Affiliated Hospital Of Nanjing Medical University,Xijing Hospital Affiliated to the Fourth Military Medical University,the Second Affiliated Hospital of Xi'an Jiaotong University between August 2006 and October 2007. The levofloxacin was set as the efficient control. Two hundred and thirty-five patients (235 eyes ) that diagnosed as bacterial conjunctivitis were randomly divided into two groups by the method of randomized blocks, the test group (gatifloxacin) had 118 eyes and the control (levofloxacin) group had 117eyes. The drug delivery into conjunctival sac was performed at a 7-day period ( two drops per time, eight times per day at the first two days and two drops per time, four times per day at the following 5 days). All participants were given the conjunetival sac germ culture and drug sensitive test before and after the study.The combination score of signs and symptoms and evaluation of safety were conducted at the pre-dilivery day,the (4 ± 1 ) and (7 ± 1 ) dilivery day. The statistic analysis was conducted by CMH X2 test, Pearson X2 test and Fisher's exact probabilities test. Results The efficacy of the two groups was 94. 0% ( 110/117 eyes)in gatifloxacin group and 93.8% ( 106/113 eyes) in levofloxacin group with no significant difference( X2 =0.052,P = 0.8201 ). There was also no difference in the bacteria clearance between the two groups [ gatifloxacin versus levofloxacin, 94.1% (80/85 eyes) versus 92. 5% (74/80 eyes) ,P =0. 3470]. The decrease of combination score of signs and symptoms at the (4 ± 1 ) delivery day was 4. 436 +2. 310 in the gatifloxacin group and 3. 814 ± 1. 962 in the levofloxacin group, the difference of which was significant ( F =7.280,P = 0. 0075 ) . This trend was also proved at the ( 7 ± 1 ) delivery day ( gatifloxacin versus levofloxacin, 7. 487 ± 2. 821 versus 6. 912 ± 2. 911, F = 4. 060, P = 0. 0452 ). The visual acuity and the tolerance after local application of the eye drops between the two groups had no diffenrence ( the visual acuity F = 1.04, P = 0. 3080; the tolarence after local admission X2 = 0. 1372, P = 0. 7111 ). According to the result of the germ culture, the major pathogenic bacteria were Gram-positive bacteria ( totally 20 kinds of Grampositive bacteria and 8 kinds of Gram-negetive bacteria). The MIC and drug resistence of gatifloxacin to the Gram-positive bacteria was lower than that of the levofloxaxin ( Staphylococcus Epidermidis, Staphylococcus Aureus, coagulase negative Staphylococcus, α-hemolytic Streptococcus). Conclusions The gatifloxacin eye drop has a good therapeutic effect to the bacterial conjunctivitis, It can effectively clear the pathogen with fast and strong effect. Moreover, it has a low MIC in vitro, advance a prospect in drug resistance, safety and ocular tolerance.
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