In vitro antiviral susceptibilities of isolates from cytomegalovirus retinitis patients receiving first- or second-line cidofovir therapy: Relationship to clinical outcome

Blood culture isolates from patients receiving first- (peripheral retinitis ) or second-line (relapsing retinitis) therapy with intravenous cidofovir w ere obtained from three clinical trials for in vitro antiviral susceptibili ty analyses. Isolates from 6 patients obtained after 14.3 weeks (mean) of f irst-line cidofovir therapy showed complete susceptibility to cidofovir, ga nciclovir, and foscarnet, Isolates from 20 patients were obtained after 17. 3 weeks (mean) of second-line cidofovir therapy. Ten showed complete suscep tibility to all inhibitors, 3 showed low-level ganciclovir resistance (<6-f old) but were sensitive to cidofovir and foscarnet, and 7 showed moderately reduced susceptibility (<8-fold) to cidofovir and high-level resistance (8 - to 23-fold) to ganciclovir in vitro. Four of these 7 isolates showed redu ced susceptibility (4-fold) to foscarnet, Notably, there was no difference in time to retinitis progression in patients that were on cidofovir therapy when sensitive isolates were compared with those showing reduced susceptib ility to cidofovir in vitro.