兔玻璃体腔注射美罗培南治疗细菌性眼内炎

Intravitreal meropenem injection against experimental bacterial endophthalmitis in rabbits

目的评价兔玻璃体腔注射国产美罗培南对敏感菌引起的眼内炎的疗效。方法选取健康成年日本大耳白兔24只,随机分为Ⅰ、Ⅱ两组,每组12只,分别玻璃体腔内接种金黄色葡萄球菌和绿脓杆菌建立相应的眼内炎模型。待出现典型眼内炎体征时,Ⅰ组和Ⅱ组再随机分为A、B组和C、D组。B、D组玻璃体腔均注射美罗培南1.25 mg,A、C组分别注射万古霉素1.0 mg和复达欣2.0 mg作为对照。通过临床炎症评分、细菌培养阳性率、组织学检查病理评分等指标评估药物疗效。结果在两种眼内炎模型中,美罗培南用药后临床炎症评分均有显著下降,用药前后相比有统计学差异,但与万古霉素、复达欣相比无统计学差异;美罗培南用药后细菌培养阳性率在金黄色葡萄球菌和绿脓杆菌眼内炎模型中分别为0和16.7%,均低于万古霉素和复达欣,与万古霉素相比差异有统计学意义;用药2周后组织学检查显示绝大多数标本视网膜组织结构基本完整,层间有不同程度变性和坏死伴炎症细胞浸润,美罗培南与万古霉素、复达欣相比其视网膜病理评分均无统计学差异。结论兔玻璃体腔注射美罗培南治疗敏感金黄色葡萄球菌和绿脓杆菌引起的眼内炎,疗效分别与万古霉素、复达欣基本相当,但当眼内炎体征已明显时单次眼内用药很难完全控制炎症。

Objective Interest in new broad-spectrum antibiotics administered intravitreally for bacterial endophthalmitis have gradually increased in recent years. The purpose of this study was to evaluate the efficacy of intravitreal meropenem injection against experimental infectious endophthalmitis. Methods The right eyes of 12 rabbits were infected with an intravitreal inoculation of 500 colony-forming units（CFU）/0. 1 ml Pseudomonas aeruginosa. Twenty-four hours after inoculation,rabbits were randomized to treat with intravitreal ceftazidime（ 6 rabbits, Group A ）and meropenem （6 rabbits, Group B）. 1.0 × 10^4 CFU/0. 1 ml of Staphylococcus aureus were injected in rabbits of other group and were randomized to treat with intravitreal vancomycin 48 hours later（ 6 rabbits, Group C ） and meropenem （ 6 rabbits, Group D）. The efficacy of intravitreal meropenem injection was evaluated by clinical examination scores according to Peyman＇ s classification, the vitreous culture results and the histopathologic examination of retina based on Park＇ s classification. Results After the administration of intravitreal meropenem,the clinical scores dropped significantly in both S. aureus and P. aeruginosa endophthalmitis models （ P 〈 0.01 ）, and no statistical differences between ceftazidime and vancomycin were found. Culture-positive rates of vitreous samples were lower in meropenem groups （ Group B： 16.7%, Group D： 0）than ceftazidime group （50.0%）and vancomycin group （66.7%）, respectively achieving statistical difference between meropenem and vancomycin groups. The histopathologic evaluation showed substantial retina infiltration of inflammatory cells and partial destruction and necrosis in almost all samples from different treatment groups. No significant difference was seen between S. aureus and P. aeruginosa endophthalmitis models（ P = 0. 147）and among different treatment groups （P 〉 0. 05 ） in histopathologic score. Conclusion The efficacy of intravitreal meropenem administration is similar to ceftazidime and vancomycin for treatment of endophthalmitis caused by sensitive bacterium in rabbits.