妥布霉素滴眼液对家兔细菌性角膜炎体内外抗菌作用

Anti-bacterial effect of Tobramycin Eye Drops against rabbit keratitis in vitro and in vivo

目的:研究妥布霉素滴眼液的抗菌作用。方法:体外采用M-H肉汤稀释法,妥布霉素滴眼液对大肠埃希菌、金黄色葡萄球菌、绿脓杆菌、化脓性链球菌、肺炎克雷伯菌、肺炎链球菌进行体外抑菌、杀菌试验。体内用角膜环钻损伤兔眼角膜,感染大肠埃希菌、金黄色葡萄球菌、绿脓杆菌、化脓性链球菌造成角膜炎动物模型。然后用妥布霉素滴眼液滴眼4次/d,每眼0.1mL,连续给药7d。d8处死家兔。以观察角膜病理切片,临床症状评分统计学t检验处理及角膜分泌物细菌培养判断疗效。结果:体外试验表明妥布霉素滴眼液对上述6种细菌最低杀菌浓度(MBC)分别为0.19,0.39,0.78,46.88,93.75,187.50μg/mL。体内抗菌试验显示,家兔眼感染大肠埃希菌、金黄色葡萄球菌、绿脓杆菌、化脓性链球菌感染后,妥布霉素滴眼液在治疗3d评分结果与未治疗对照组比较均有显著差异,5d细菌培养转阴率大肠埃希菌、金黄色葡萄球菌、绿脓杆菌均为100%,化脓性链球菌83%。角膜病理结果显示除化脓性链球菌伤口愈合较慢,余3种菌伤口斑痕愈合良好。结论:妥布霉素滴眼液对大肠埃希菌、金黄色葡萄球菌、绿脓杆菌敏感性较强;所致家兔角膜炎治疗效果较好,化脓性链球菌、肺炎克雷伯菌、肺炎链球菌对其敏感性较弱。

AIM： To investigate the anti-bactedal efficacy of Tobramydn Eye Drops against experimental keratitis on rabbits. HETHODS： Tobramycin Eye Drops was stocked in 1g/L by PBS, diluted in half concentration by M-H meat soup with addition of six different bacteria （10^10 CFU/L）, which are Escherichia coil, Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pyogenes, Klebsiella pneumoniae, and Streptococcus pneumoniae, and subject to experimentation. Rabbit model of keratitis was made by scratching parenchymal layer of cornea by corneal trephine with addition of 0.1 mL bacterial dilution （2×10^12 CFU/L）per eyes, then the eyes were treated with Tobramycin Eye Drops q.i.d, in seven successive days, 0.1mL At eighth day, the rabbits were executed, and the cornea was sliced for pathological examination. Corneal secretions were subject to bacterial culture one day before treatment and 1, 3, and 5 post-treatment. Evaluation scoring based on rabbit clinical manifestations was processed by t -test. RESULTS： In vitro test, the minimal bactericidal concentration of Tobramydn Eye Drops were 0.19, 0.39, 0.78, 46.88, 93.75, 187.50μg/mL for E coli, S aureus, P. aeruginosa, S. pyogenes, K. pneumoniae, and S pneumoniae, respectively. In vivo test, evaluation scoring of Tobramydn Eye Drops at third day was significantly different compared with the control group, while bacterial culture from corneal secretion were 100% negative for E coli, S. aureus, P. aeruginosa, and 83% negative for S. pyogenes at fifth day. Pathological examination results of the corneal sections demonstrated that the healing of keratitis was well enough for the first three bacteria and slower for S. pyogenes. CONCLUSION： Tobramycin Eye Drops treats effectively for E. coli, S. aureus, and P. aeruginosa, but poorly for S. pyogenes, K. pneumoniae, and S. pneumoniae.