HSV1 strain sensitivity in experimental rabbit keratitis: evolution under repeated topical IDU administrations.
The effects of repeated topical idoxuridine (IDU) administration of HSV1 strain sensitivity were investigated during 6 serial passages (P1 to P6) in the rabbit. By comparison to placebo treated rabbits, a delay in ulcer cicatrization appeared at P2 and clinical resistance was completed at P3. Clinical cross resistance to acyclovir (ACV) was also tested and demonstrated at P7. In vitro, a plaque reduction test on Vero cells using directly the tear film HSV populations allowed the prediction of the resistance by an early rise in the effective dose 90% (ED 90) value anticipating that in ED 50%. An ED 50 determination by dye-uptake assay on P6 HSV isolate demonstrated a cross resistance to viral thymidine kinase (TK) dependent drugs without any change in Ara-A and PFA sensitivity, according to a 23% TK activity at P6. At the last passage the HSV drug resistant population had an unrestricted corneal pathogenicity. A return to IDU and ACV in vitro sensitivity was demonstrated in group control animals at P2 but not at P4 or P6.
D000212:Acyclovir / Q000627:therapeutic use; D000818:Animals; D004352:Drug Resistance, Microbial; D005260:Female; D007065:Idoxuridine / Q000627:therapeutic use*; D007635:Keratitis, Dendritic / Q000188:drug therapy* / Q000382:microbiology; D011817:Rabbits; D018139:Simplexvirus / Q000472:pathogenicity / Q000502:physiology*; D010948:Viral Plaque Assay
D007065:Idoxuridine; D000212:Acyclovir