In vitro and in vivo effects of polyhexamethylene biguanide against herpes simplex virus infection.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Valluri
S
S
Department of Ophthalmology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Fleming
T P
TP
Laycock
K A
KA
Tarle
I S
IS
Goldberg
M A
MA
Garcia-Ferrer
F J
FJ
Essary
L R
LR
Pepose
J S
JS
D000287:Administration, Topical; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D001645:Biguanides / Q000008:administration & dosage / Q000627:therapeutic use*; D002417:Cattle; D003315:Cornea / Q000187:drug effects* / Q000294:innervation / Q000821:virology; D004195:Disease Models, Animal; D004202:Disinfectants / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005500:Follow-Up Studies; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000276:immunology; D016849:Keratitis, Herpetic / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D009883:Ophthalmic Solutions; D011817:Rabbits; D016896:Treatment Outcome
D000914:Antibodies, Viral; D001645:Biguanides; D004202:Disinfectants; D009883:Ophthalmic Solutions; C031233:polihexanide