Valluri S, Fleming T P, Laycock K A, Tarle I S, Goldberg M A, Garcia-Ferrer F J, Essary L R, Pepose J S
Department of Ophthalmology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Cornea. 1997 Sep;16(5):556-9.
The differential diagnosis of Acanthamoeba keratitis frequently includes herpes simplex viral keratitis. Previous in vitro studies with chlorhexidine, a drug with antiacanthamoebic action, have suggested concomitant antiviral activity against herpes simplex virus. We tested another related antiacanthamoebic compound, polyhexamethylene biguanide (PHMB), to determine its activity against herpes simplex virus (HSV) in vitro and herpes simplex viral keratitis in vivo.
Equal aliquots of HSV-1 (McKrae) strain were incubated in a medium with no PHMB or with PHMB at 0.01, 0.02, or 0.05 for 5 min at 35 degrees C and the inoculum was then titered on a monolayer of E-2 cells (human corneal fibroblasts). Monolayers were examined on consecutive days and the percentage of plaque reduction was calculated. Eighteen rabbits (36 eyes) were inoculated with HSV-1 McKrae strain (10(5) pfu [plaque-forming units]/per eye). Rabbits were divided into three groups and treatment was initiated on day 3 postinfection. Group I received trifluorothymidine, group II received PHMB, and group III received artificial tears, each given five times daily in both eyes until day 10. Daily corneal swabbing to detect viral shedding and slit-lamp examination every 3 days were performed during this period.
In vitro studies showed 62.5, 100, and 100% plaque reduction with 0.01, 0.02, and 0.05% PHMB, respectively. Slit-lamp examination of the rabbit corneas revealed faster resolution of dendrites in animals in group I treated with trifluorothymidine. Virus was not recoverable from corneal swabs in nine of 10 rabbits in group I by day 5, but all animals in groups II and III were still shedding HSV through day 8.
Although PHMB has potent in vitro activity against HSV, it was not an effective treatment in the in vivo rabbit model of primary HSV keratitis at the concentration commonly used for treatment of Acanthamoeba infection. This suggests that 0.02% PHMB will not provide adequate antiherpetic coverage with treatment of keratitis of undetermined etiology in which the clinical differential diagnosis includes both herpes simplex and Acanthamoeba.
棘阿米巴角膜炎的鉴别诊断通常包括单纯疱疹病毒性角膜炎。先前使用具有抗棘阿米巴作用的药物洗必泰进行的体外研究表明，其对单纯疱疹病毒具有抗病毒活性。我们测试了另一种相关的抗棘阿米巴化合物聚六亚甲基双胍（PHMB），以确定其在体外对单纯疱疹病毒（HSV）以及在体内对单纯疱疹病毒性角膜炎的活性。
将等量的HSV-1（McKrae）毒株在不含PHMB或含有0.01%、0.02%或0.05%PHMB的培养基中于35℃孵育5分钟，然后将接种物接种于E-2细胞（人角膜成纤维细胞）单层上进行滴定。连续几天检查单层细胞，并计算蚀斑减少的百分比。18只兔子（36只眼）接种HSV-1 McKrae毒株（每只眼10⁵ 蚀斑形成单位）。兔子被分为三组，在感染后第3天开始治疗。第一组接受三氟胸腺嘧啶，第二组接受PHMB，第三组接受人工泪液，每组每天双眼给药5次，直至第10天。在此期间，每天进行角膜拭子检查以检测病毒脱落情况，并每3天进行一次裂隙灯检查。
体外研究显示，0.01%、0.02%和0.05%的PHMB分别使蚀斑减少62.5%、100%和100%。对兔角膜的裂隙灯检查显示，用三氟胸腺嘧啶治疗的第一组动物的树枝状溃疡愈合更快。到第5天，第一组10只兔子中有9只的角膜拭子中未检测到病毒，但第二组和第三组的所有动物在第8天仍在排出HSV。
尽管PHMB在体外对HSV具有强大的活性，但在用于治疗棘阿米巴感染的常用浓度下，它在原发性HSV角膜炎的体内兔模型中并非有效治疗方法。这表明，对于病因未明的角膜炎，当临床鉴别诊断包括单纯疱疹和棘阿米巴时，0.02%的PHMB不能提供足够的抗疱疹病毒覆盖范围。
