[Resistance to virostatic agents in Herpes viruses: mechanism, incidence and clinical significance].
Following the introduction of potent antiviral agents against herpes simplex virus (HSV), varicella-zoster virus (VZV), and cytomegalovirus (CMV) into clinical use, the isolation of resistant virus strains has been reported with increasing frequency. The first part of this overview focuses on the mechanisms of action of acyclovir, ganciclovir, and forcarnet, and on the mechanisms of viral resistance. In the second part, the incidence and clinical importance of resistant herpes viruses are discussed. Among immunocompetent patients, herpes virus resistance is a rare event even in the case of long-term treatment with acyclovir for suppression of genital herpes. By contrast, among immunocompromised hosts, the isolation of resistant herpes virus strains from patients with disease unresponsive to antiviral drugs is not infrequent. The incidence of acyclovir-resistant HSV isolates in two large studies was 5%, and that of ganciclovir-resistant CMV strains was reported to be about 7%. At present, data on infections due to resistant VZV strains are scarce. Results from case reports and small series suggest some clinical benefit from the use of foscarnet when acyclovir-resistant HSV or VZV is present, or when CMV disease is caused by ganciclovir-resistant strains. Broader use of susceptibility testing to antiviral drugs and the development of new antiherpetic agents are required to improve the diagnosis and treatment of disease due to resistant herpes viruses.
Reusser
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Departement für Innere Medizin, Kantonsspital Basel.
D000212:Acyclovir / Q000378:metabolism / Q000494:pharmacology; D000998:Antiviral Agents / Q000378:metabolism / Q000494:pharmacology*; D004351:Drug Resistance; D017245:Foscarnet / Q000494:pharmacology; D015774:Ganciclovir / Q000494:pharmacology; D006564:Herpesviridae / Q000187:drug effects*; D006801:Humans; D007121:Immunocompetence; D016867:Immunocompromised Host; D010766:Phosphorylation
D000998:Antiviral Agents; D017245:Foscarnet; D015774:Ganciclovir; D000212:Acyclovir
Virostatika-Resistenz bei Herpesviren: Mechanismen, Häufigkeit und klinische Bedeutung.