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

Abstract

Blood culture isolates from patients receiving first- (peripheral retinitis) or second-line (relapsing retinitis) therapy with intravenous cidofovir were obtained from three clinical trials for in vitro antiviral susceptibility analyses. Isolates from 6 patients obtained after 14.3 weeks (mean) of first-line cidofovir therapy showed complete susceptibility to cidofovir, ganciclovir, and foscarnet. Isolates from 20 patients were obtained after 17.3 weeks (mean) of second-line cidofovir therapy. Ten showed complete susceptibility to all inhibitors, 3 showed low-level ganciclovir resistance (<6-fold) 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 reduced 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 susceptibility to cidofovir in vitro.