Treatment of Cytomegalovirus Retinitis with Trisodium Phosphonoformate Hexahydrate (Foscarnet)

Walmsley, Sharon; Chew, Emily Y.; Read, Stanley; Vellend, Hillar; Salit, Irving E.; Rachlis, Anita; Fanning, Mary M.

doi:10.1093/infdis/157.3.569

Cited by 152 publications

(43 citation statements)

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“…The relationship of renal insufficiency to foscarnet use was considered possible in 4 of these 5 patients and was judged unevaluatable in the other. The frequency and severity ofrenal toxicity in our study was in the range ofthat in other studies ofallogeneic BMT recipients and AIDS patients [24,25,[28][29][30][31][32].…”

Section: Discussionsupporting

confidence: 64%

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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Section: Discussionsupporting

confidence: 64%

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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“…PFA may offer a therapeutic alternative in cases of GCV-resistant virus infections or in cases of patient intolerance of GCV. Early studies with small numbers of patients indicate that PFA is effective for the treatment of CMV disease (24,26,37,43). PFA has the advantage that it can be administered concurrently with zidovudine, since the adverse events of PFA are primarily renal and metabolic rather than hematologic (24,26,37,43).…”

Section: Discussionmentioning

confidence: 99%

Ganciclovir-resistant cytomegalovirus clinical isolates: mode of resistance to ganciclovir

Stanat

Reardon

Erice

et al. 1991

Antimicrob Agents Chemother

166

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Cytomegalovirus strains with reduced in vitro susceptibilities to ganciclovir have been recovered from patients who failed long-term ganciclovir therapy. The ganciclovir-resistant clinical isolates in this study were unable to induce ganciclovir phosphorylation in virus-infected cells. The viral DNA polymerase function appeared unaltered in one genetically pure ganciclovir-resistant strain, compared with that of its wild-type ganciclovir-sensitive counterpart. All nine of the ganciclovir-resistant strains were susceptible to foscarnet. Moreover, these strains were sensitive to inhibition both by vidarabine and 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine (FIAC), antiviral agents that are activated by cellular enzymes, and by (S)-1(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC), which is a monophosphate nucleoside analog. The in vitro resistance to ganciclovir of the ganciclovir-resistant clinical isolates studied was attributed to the inability of the cells infected with these isolates to phosphorylate ganciclovir; the virally encoded DNA polymerase did not appear to play a role in this ganciclovir resistance.

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“…The importance of such deposition, especially for bone development in children, is not known. The major adverse effects of foscarnet are renal impairment (present in most patients and dose limiting in 10 to 23% of them), imbalances of electrolytes such as calcium, phosphate, potassium, and magnesium (101,134,221,224,382,495), and seizures (7). It appears that foscamet chelates divalent metal ions such as calcium, resulting in a doserelated but reversible drop in serum calcium that may be severe or even fatal (223).…”

Section: Foscarnetmentioning

confidence: 99%

“…Vision stabilized or improved in 80 to 100% of patients, but maintenance therapy was required, and even so, 70% or more relapsed (134,224,274,336,495). The potential advantage of foscarnet in this setting is that it has less bone marrow toxicity than ganciclovir, and it may be possible to use it in conjunction with zidovudine.…”

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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Treatment of Cytomegalovirus Retinitis with Trisodium Phosphonoformate Hexahydrate (Foscarnet)

Cited by 152 publications

References 0 publications

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

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

Ganciclovir-resistant cytomegalovirus clinical isolates: mode of resistance to ganciclovir

Antiviral therapy: current concepts and practices

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