title: 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.
authors.affiliation: Gilead Sciences, Inc., Foster City, CA 94404, USA. julie_cherrington@gilead.com
authors.forename: J M
authors.initials: JM
authors.lastname: Cherrington
authors.forename: M D
authors.initials: MD
authors.lastname: Fuller
authors.forename: P D
authors.initials: PD
authors.lastname: Lamy
authors.forename: R
authors.initials: R
authors.lastname: Miner
authors.forename: J P
authors.initials: JP
authors.lastname: Lalezari
authors.forename: S
authors.initials: S
authors.lastname: Nuessle
authors.forename: W L
authors.initials: WL
authors.lastname: Drew
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D000077404:Cidofovir; D003587:Cytomegalovirus / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D017726:Cytomegalovirus Retinitis / Q000188:drug therapy* / Q000821:virology; D003596:Cytosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004352:Drug Resistance, Microbial; D017245:Foscarnet / Q000494:pharmacology; D015774:Ganciclovir / Q000494:pharmacology; D005838:Genotype; D006801:Humans; D008826:Microbial Sensitivity Tests; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000627:therapeutic use*; D012008:Recurrence
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D017245:Foscarnet; D003596:Cytosine; D000077404:Cidofovir; D015774:Ganciclovir