Cidofovir microbiology

Cidofovir
VISTIDE® FDA Package Insert
Description
Clinical Pharmacology
Microbiology
Indications and Usage
Contraindications
Warnings and Precautions
Adverse Reactions
Drug Interactions
Overdosage
Clinical Studies
Dosage and Administration
How Supplied
Labels and Packages

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Microbiology

In Vitro Susceptibility

Cidofovir is active in vitro against a variety of laboratory and clinical isolates of cmv and other herpesviruses (Table 1). Controlled clinical studies of efficacy have been limited to patients with AIDS and cmv retinitis.

Resistance

cmv isolates with reduced susceptibility to cidofovir have been selected in vitro in the presence of high concentrations of cidofovir4. IC50 values for selected resistant isolates ranged from 7–15 µM.

There are insufficient data at this time to assess the frequency or the clinical significance of the development of resistant isolates following VISTIDE administration to patients.

The possibility of viral resistance should be considered for patients who show a poor clinical response or experience recurrent retinitis progression during therapy.

Cross Resistance

Cidofovir-resistant isolates selected in vitro following exposure to increasing concentrations of cidofovir were assessed for susceptibility to Ganciclovir and foscarnet4. All were cross resistant to Ganciclovir, but remained susceptible to foscarnet. [[Ganciclovir]]- or Ganciclovir/foscarnet-resistant isolates that are cross resistant to cidofovir have been obtained from drug naive patients and from patients following Ganciclovir or Ganciclovir/ foscarnet therapy. To date, the majority of Ganciclovir-resistant isolates are UL97 gene product (phosphokinase) mutants and remain susceptible to cidofovir5. Reduced susceptibility to cidofovir, however, has been reported for DNA polymerase mutants of cmv which are resistant to Ganciclovir6–9. To date, all clinical isolates which exhibit high level resistance to Ganciclovir, due to mutations in both the DNA polymerase and UL97 genes, have been shown to be cross resistant to cidofovir. Cidofovir is active against some, but not all, cmv isolates which are resistant to foscarnet10–12. The incidence of foscarnet-resistant isolates that are resistant to cidofovir is not known.

A few triple-drug resistant isolates have been described. Genotypic analysis of two of these triple-resistant isolates revealed several point mutations in the cmv DNA polymerase gene. The clinical significance of the development of these cross-resistant isolates is not known.

References

Adapted from the FDA Package Insert.