[Comparison of the in vitro sensitivity to cidofovir and ganciclovir of clinical cytomegalovirus isolates. Coordinated Action Group 11].
Cidofovir (CDF) or Vistid is a monophosphate nucleoside analogue that inhibits the DNA polymerase of herpes viruses including the cytomegalovirus (CMV). CDF is active on GCV-resistant strains with a mutation on the phosphotransferase gene (UL97). However, DNA polymerase gene mutations that induce resistance to GCV are responsible for cross-resistance to CDF. Resistance phenotypes to GCV and CDF were determined for 57 CMV strains isolated from blood and urine samples. Sixteen strains were recovered after CDF therapy. Of the remaining 41 CDF-naive strains, 34 were susceptible and seven resistant to GCV. Fifty percent inhibitory concentrations (IC50) for CDF were in the 0.2-2.6 microM range for CDF-naive strains susceptible to GCV. For GCV-resistant strains, IC50 values for CDF were < or = 3 microM for strains with a low level of resistance to GCV (GCV IC50 < 30 microM) and > or = 6 microM for three of the five strains with a high level of resistance to GCV (GCV IC50 > or = 30 microM).
Houhou-Fidouh
N
N
Laboratoire de Virologie, CHU Bichat Claude-Bernard, Paris, France.
Mazeron
M C
MC
Dewilde
A
A
Thouvenot
D
D
Scieux
C
C
Aissa
N
N
Carquin
J
J
Freymuth
F
F
D000998:Antiviral Agents / Q000494:pharmacology*; D000077404:Cidofovir; D003587:Cytomegalovirus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D003596:Cytosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D018432:Drug Resistance, Multiple; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015774:Ganciclovir / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D019384:Nucleic Acid Synthesis Inhibitors; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D014764:Viral Proteins / Q000037:antagonists & inhibitors / Q000235:genetics
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D019384:Nucleic Acid Synthesis Inhibitors; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D014764:Viral Proteins; D003596:Cytosine; D017853:Phosphotransferases (Alcohol Group Acceptor); C075365:ganciclovir kinase; D000077404:Cidofovir; D015774:Ganciclovir
Comparaison de la sensibilité in vitro au cidofovir et au ganciclovir des isolats cliniques de cytomégalovirus. Groupe de l'Action Coordonnée 11.