Foscarnet microbiology
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Microbiology
Antiviral Activity in vitro and in vivo
The quantitative relationship between the in vitro susceptibility of human cytomegalovirus (CMV) or herpes simplex virus 1 and 2 (HSV-1 and HSV-2) to FOSCAVIR and clinical response to therapy has not been established and virus sensitivity testing has not been standardized. Sensitivity test results, expressed as the concentration of drug required to inhibit by 50% the growth of virus in cell culture (IC50), vary greatly depending on the assay method used, cell type employed and the laboratory performing the test. A number of sensitive viruses and their IC50 values are listed below (Table 1).
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Statistically significant decreases in positive CMV cultures from blood and urine have been demonstrated in two studies (FOS-03 and ACTG-015/915) of patients treated with FOSCAVIR. Although median time to progression of CMV retinitis was increased in patients treated with FOSCAVIR, reductions in positive blood or urine cultures have not been shown to correlate with clinical efficacy in individual patients.
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Resistance
Strains of both HSV and CMV that are resistant to FOSCAVIR can be readily selected in vitro by passage of wild type virus in the presence of increasing concentrations of the drug. All FOSCAVIR resistant mutants are known to be generated through mutation in the viral DNA polymerase gene. CMV strains with double mutations conferring resistance to both FOSCAVIR and ganciclovir have been isolated from patients with AIDS. The possibility of viral resistance should be considered in patients who show poor clinical response or experience persistent viral excretion during therapy.[1]
References
- ↑ "http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020068s018lbl.pdf" (PDF). External link in
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Adapted from the FDA Package Insert.