Combined and alternating ganciclovir and foscarnet in acute and maintenance therapy of human immunodeficiency virus-related cytomegalovirus encephalitis refractory to ganciclovir alone

Abstract

Cytomegalovirus (CMV) causes life-threatening disseminated infections and in particular vision-threatening infections of the retina in patients with the acquired immunodeficiency syndrome. Ganciclovir currently represents the most frequently used therapy for CMV retinitis. However, cases of ganciclovir-resistant CMV strains have been described, in which foscarnet seems to be an effective alternative. Both drugs have serious toxicities, and relapses frequently occur during maintenance therapy. In a patient with CMV encephalitis, we administered a 3-week combination ganciclovir/foscarnet induction therapy (ganciclovir 5 mg/kg every 12 h; foscarnet 60 mg/kg every 8 h), followed by an alternating maintenance administration of both drugs every other day (ganciclovir 5 mg/kg, foscarnet 120 mg/kg) to reduce toxicity and resistance. This regimen was tolerated well and seemed to be more effective than ganciclovir alone in a patient with CMV encephalitis.

Successful treatment of cytomegalovirus encephalitis in a patient with Hodgkin's disease in remission

“…Progression of CMV retinitis can also occur in patients under maintenance therapy with foscarnet. Synergism between ganciclovir and foscarnet has been reported in vitro, and some clinical data are supportive of a similar phenomenon in vivo, in CMV retinitis and in encephalitis [6,11].…”

“…Ganciclovir is a guanarine derivative and the firstchoice treatment, but ganciclovir-resistant strains have been reported [11]. Foscarnet is an alternative therapeutic approach because it does not require phosphorylation to be active (as does ganciclovir).…”

Relevance of clinical and laboratory findings in the diagnosis of cytomegalovirus encephalitis in patients with AIDS

“…A possible therapeutic approach in these patients could be to combine ganciclovir and foscarnet. These agents show synergy in vitro (41) and, used together, gave good results in both CMV-related neurological and extraneurological infection (29,(42)(43)(44).…”

Summary of the II international consensus symposium on combined antiviral therapy and implications for future therapies

“…Sufficient penetration of the blood-brain barrier is a concern, as is the development of viral resistance since CNS disease often occurs in patients receiving long-term maintenance therapy for CMV retinitis. Uncontrolled case-series suggest a benefit of combined treatment with ganciclovir and foscarnet in the treatment of CMV encephalitis (Enting et al, 1992;Peters et al, 1992).…”