IN-VITRO AND IN-VIVO EFFECTS OF POLYHEXAMETHYLENE BIGUANIDE AGAINST HERPES-SIMPLEX VIRUS-INFECTION

Purpose, The differential diagnosis of Acanthamoeba keratitis frequent ly includes herpes simplex viral keratitis. Previous in vitro studies with chlorhexidine, a drug with antiacanthamoebic action, have suggest ed concomitant antiviral activity against herpes simplex virus. We tes ted another related antiacanthamoebic compound, polyhexamethylene bigu anide (PHMB), to determine its activity against herpes simplex virus ( HSV) in vitro and herpes simplex viral keratitis in vivo. Methods. Equ al aliquots of HSV-1 (McKrae) strain were incubated in a medium with n o PHMB or with PHMB at 0.01, 0.02, or 0.05 for 5 min at 35 degrees C a nd the inoculum was then titered on a monolayer of E-2 cells (human co rneal fibroblasts). Monolayers were examined on consecutive days and t he percentage of plaque reduction was calculated. Eighteen rabbits (36 eyes) were inoculated with HSV-1 McKrae strain (10(5) pfu [plaque-for ming units]/per eye). Rabbits were divided into three groups and treat ment was initiated on day 3 postinfection. Group I received trifluorot hymidine, group IT received PHMB, and,group III received artificial te ars, each given five times daily in both eyes until day 10. Daily corn eal swabbing to detect viral shedding and slit-lamp examination every 3 days were performed during this period. Results, In vitro studies sh owed 62.5, 100, and 100% plaque reduction with 0.01, 0.02, and 0.05% P HMB, respectively. Slit-lamp examination of the rabbit corneas reveale d faster resolution of dendrites in animals in group I treated with tr ifluorothymidine. 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 I II were still shedding HSV through day 8. Conclusion, Although PHMB ha s potent in vitro activity against HSV, it was not an effective treatm ent in the in vivo rabbit model of primary HSV keratitis at the concen tration commonly used for treatment of Acanthamoeba infection. This su ggests that 0.02% PHMB will not provide adequate antiherpetic coverage with treatment of keratitis of undetermined etiology in which the cli nical differential diagnosis includes both herpes simplex and Acantham eba.