Foscarnet for Cytomegalovirus Pneumonitis

Apperley, J.F.; Marcus, Robert; Goldman, J M; Wardle, D.; Gravett, Peter; Chañas, A. C.

doi:10.1016/s0140-6736(85)92447-x

Cited by 24 publications

(3 citation statements)

References 3 publications

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“…FUdR and PFA also have antiviral activity against CMV (Goodheart et al, 1963;Wahren & Oberg, 1980) but with a different mode of action to DHPG and both have been clinically evaluated (Cangir et al, 1967;Feigin et al, 1971 ;Apperley et al, 1985;Ringden et al, 1985).…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Cytomegalovirus DNA Is an Antiviral Target Late in Virus Growth

Tyms

Davis

Clarke

et al. 1987

Journal of General Virology

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SUMMARYThe mechanism of action of %(1,3-dihydroxypropoxymethyl)guanine (DHPG) and phosphonoformic acid (PFA) but not 5-fluorouridinedeoxyribose (FUdR), provides selective action against cytomegalovirus (CMV)-coded events and this was used to demonstrate that the synthesis of viral DNA was continuous during the extended phase of virus growth. The synthesis de novo of viral DNA was measured by restriction enzyme analysis after exposure to [32p]orthophosphate and its interruption by DHPG or PFA resulted in a cessation in the extrusion of infective virus from treated cells. The rate of decline in infectivity appeared to correspond to the failure of cells to maintain the synthesis of late proteins once DNA synthesis was blocked. Thus, regulation of late protein synthesis appeared to be linked to synthesis de novo of viral DNA even at late stages in CMV growth. The synthesis of the polyamines spermidine and spermine, considered obligatory for CMV growth, was unaffected by early or late inhibition of viral DNA and this showed that some virus-induced events were unaffected by the restriction on virus growth by DHPG. This provided evidence that polyamine biosynthesis was a target independent of viral DNA synthesis per se, which may be important in future considerations of combined drug therapies.

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Section: Introductionmentioning

confidence: 99%

Synthesis of Cytomegalovirus DNA Is an Antiviral Target Late in Virus Growth

Tyms

Davis

Clarke

et al. 1987

Journal of General Virology

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“…With one exception [17], earlier studies of foscarnet among BMT recipients used continuous intravenous infusions to administer the drug [13,19,28,29,[36][37][38]. In one of these studies that reported data on pharmacokinetics [29], the steady-state serum levels of foscarnet in 13 allogeneic BMT recipients who received a daily dose of foscarnet similar to the dose in our inpatient regimen were 273 ± 43~mol/ L (mean ± SE).…”

Section: Discussionmentioning

confidence: 89%

Phase I-II Trial of Foscarnet for Prevention of Cytomegalovirus Infection in Autologous and Allogeneic Marrow Transplant Recipients

Reusser

Gambertoglio

Lilleby

et al. 1992

Journal of Infectious Diseases

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The safety and efficacy of foscarnet for prevention of cytomegalovirus (CMV) infection was evaluated in 19 CMV-seropositive bone marrow transplant (BMT) recipients. All patients received intermittent intravenous (iv) foscarnet: 40 mg/kg every 8 h from 7 days before to day 30 after BMT, then 60 mg/kg once a day until day 75. The main toxicity was transient renal dysfunction, with a >50 pmol/L increase in serum creatinine above baseline in 5 of the 7 autograft recipients and in 6 of the 12 allograft recipients. Only 4 allograft recipients developed CMV infection during foscarnet prophylaxis, and no patient showed evidence ofCMV disease. Because 3 allograft recipients receiving concomitant iv amphotericin B showed rapid impairment of renal function, foscarnet prophylaxis should not be given to allograft recipients requiring amphotericin B; otherwise, foscarnet prophylaxis at this dose appears safe after BMT.Infection due to cytomegalovirus (CMV) causes significant morbidity and mortality among bone marrow transplant (BMT) recipients [1]. In two published series, the probability ofCMV infection within the first 100 days after BMT among patients who were CMV-seropositive before transplant was up to 80%and 60%for allograft and autograft recipients, respectively [2,3]. Mortality was primarily related to CMV pneumonia, which developed in 37% of allograft and in 22% of autograft recipients who had evidence of active CMV infection [2,3]. Thus, the prevention of CMV infection and disease after BMT is of foremost importance.Antiviral chemotherapy aimed at preventing reactivation of latent virus may be the most promising approach to CMV prophylaxis both among CMV-seropositive autograft and allograft recipients and among seronegative allograft recipients who have a seropositive marrow donor. CMV drug prophylaxis should cover the early period after BMT in which a deficiency in CMV-specific immunity can contribute to the risk of severe CMV disease [4].The antiviral agent acyclovir given intravenously at high doses was shown to be partially effective in preventing CMV infection and disease among seropositive BMT recipients [5].

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“…Other uncontrolled trials have indicated that some bone marrow and renal transplant patients with severe CMV pneumonia or with fever and leukopenia may improve with foscarnet therapy. Many died, however, and in the absence of a control group, it is difficult to assess the value of therapy in these patients (4,238,382).…”

Section: Foscarnetmentioning

confidence: 99%

Antiviral therapy: current concepts and practices

Bean

1992

Clin Microbiol Rev

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Drugs capable of inhibiting viruses in vitro were described in the 1950s, but real progress was not made until the 1970s, when agents capable of inhibiting virus-specific enzymes were first identified. The last decade has seen rapid progress in both our understanding of antiviral therapy and the number of antiviral agents on the market. Amantadine and ribavirin are available for treatment of viral respiratory infections. Vidarabine, acyclovir, ganciclovir, and foscarnet are used for systemic treatment of herpesvirus infections, while ophthalmic preparations of idoxuridine, trifluorothymidine, and vidarabine are available for herpes keratitis. For treatment of human immunodeficiency virus infections, zidovudine and didanosine are used. Immunomodulators, such as interferons and colony-stimulating factors, and immunoglobulins are being used increasingly for viral illnesses. While resistance to antiviral drugs has been seen, especially among AIDS patients, it has not become widespread and is being intensely studied. Increasingly, combinations of agents are being used: to achieve synergistic inhibition of viruses, to delay or prevent resistance, and to decrease dosages of toxic drugs. New approaches, such as liposomes carrying antiviral drugs and computer-aided drug design, are exciting and promising prospects for the future.

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Foscarnet for Cytomegalovirus Pneumonitis

Cited by 24 publications

References 3 publications

Synthesis of Cytomegalovirus DNA Is an Antiviral Target Late in Virus Growth

Synthesis of Cytomegalovirus DNA Is an Antiviral Target Late in Virus Growth

Phase I-II Trial of Foscarnet for Prevention of Cytomegalovirus Infection in Autologous and Allogeneic Marrow Transplant Recipients

Antiviral therapy: current concepts and practices

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