The effect of cidofovir on cytomegalovirus-induced hearing loss in a Guinea pig model.
OBJECTIVE
To evaluate the utility of therapy with the cyclic cogener of the anti-cytomegalovirus (CMV) agent cidofovir against CMV-induced hearing loss in a guinea pig model.


METHODS
Thirty-six guinea pigs were randomly divided into 4 groups of 9. All groups underwent auditory brainstem response testing on days 0, 4, 7, 14, 21, and 28. Group 1 received no intervention. Group 2 underwent sham surgery consisting of unilateral round window injection of 25 microL of sterile viral media on day 0. Groups 3 and 4 underwent round window injection of 1.7 x 10(5) plaque-forming units of guinea pig CMV on day 0. Group 4 received antiviral treatment with intraperitoneal injection of cidofovir (20 mg/kg) on days 1 and 5 after inoculation.


METHODS
An animal research facility.


METHODS
Thirty-six weanling Hartley guinea pigs.


RESULTS
Of the animals who received guinea pig CMV and no cidofovir treatment, 4 of 9 (day 4) and 5 of 9 (days 7 and 28) demonstrated a hearing loss of at least 30 dB. In contrast, none of the animals in the untreated, sham surgery, or cidofovir-treated groups had a hearing loss of greater than 20 dB. This difference was statistically significant for day 4 (P = .04, 1-tailed Fisher exact test), day 7 (P = .01), and day 28 (P = .01). Histologic evaluation of hearing-impaired animals revealed inflammatory infiltrates, particularly in the scala tympani. Fibrosis of the basal turn of the cochlea was observed in 7 of 9 untreated animals and 1 of 9 treated animals.


CONCLUSIONS
Cidofovir therapy prevents CMV-induced hearing loss and associated histologic changes in guinea pigs.
White
David R
DR
Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, Charleston, USA. whitedr@musc.edu
Choo
Daniel I
DI
Stroup
Greg
G
Schleiss
Mark R
MR
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D000077404:Cidofovir; D003586:Cytomegalovirus Infections / Q000150:complications*; D003596:Cytosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004195:Disease Models, Animal; D005072:Evoked Potentials, Auditory; D006168:Guinea Pigs; D034381:Hearing Loss / Q000188:drug therapy* / Q000821:virology; D063065:Organophosphonates / Q000494:pharmacology*; D011897:Random Allocation; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000998:Antiviral Agents; D063065:Organophosphonates; D003596:Cytosine; D000077404:Cidofovir