Intravenous Foscarnet for the Treatment of Severe Cytomegalovirus Infection in Allograft Recipients

Klintmalm, Göran B.; Lönnqvist, B; Öberg, Bo; Gahrton, Gösta; Lernestedt, John-Olof; Lundgren, G; Ringdén, Olle; Robért, Karl‐Henrik; Wahrén, Britta; Groth, Carl‐Gustav

doi:10.3109/inf.1985.17.issue-2.06

Cited by 103 publications

(16 citation statements)

References 19 publications

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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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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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“…In the absence of therapy, this infection inevitably leads to irreversible retinal necrosis and can progress to permanent blindness. Only two drugs, 9-(1,3-dihydroxy-2-propoxymethyl)guanine (ganciclovir, DHPG, 2'-NDG, or BIOLF-62) and phosphonoformate (foscavir, Foscamet, or PFA), have been investigated with some success as possible treatments against HCMV infections (8,20,21,25,28,35,40). PFA, an analog of pyrophosphate, has the unique property of being effective against both HIV-1 and HCMV in vitro (5,24,30,31,39,42).…”

mentioning

confidence: 99%

Combinations of 3'-azido-3'-deoxythymidine (zidovudine) and phosphonoformate (foscarnet) against human immunodeficiency virus type 1 and cytomegalovirus replication in vitro

Eriksson

Schinazi

1989

Antimicrob Agents Chemother

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Combinations of 3'-azido-3'-deoxythymidine and phosphonoformate produced a moderate synergistic inhibitory effect against human immunodeficiency virus type 1 in vitro at concentrations that are easily achieved in humans. The synergistic effect was more pronounced with increasing concentrations and was not secondary to toxic effects of the drugs. 3'-Azido-3'-deoxythymidine neither inhibited the replication of human cytomegalovirus in human embryonic lung fibroblasts nor interfered with the anticytomegalovirus effect of phosphonoformate. By using partially purified reverse transcriptase of human immunodeficiency virus type 1 and human cytomegalovirus DNA polymerase, various combinations of 3'-azido-3'-deoxythymidine-5'-triphosphate and phosphonoformate produced strong indications of additive interactions. The synergistic interactions in infected cells and the additive effects observed at the reverse transcriptase level indicate that mechanisms other than the reverse transcriptase may be of importance for the inhibition of human immunodeficiency virus replication by these two compounds. A concomitant treatment of cytomegalovirus infections, such as cytomegalovirus retinitis, with phosphonoformate in patients with acquired immunodeficiency syndrome receiving 3'-azido-3'-deoxythymidine may be appropriate, and this combination may also be useful in controlling human immunodeficiency virus infection.

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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: Discussionmentioning

confidence: 52%

“…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: 99%

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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Intravenous Foscarnet for the Treatment of Severe Cytomegalovirus Infection in Allograft Recipients

Cited by 103 publications

References 19 publications

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

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

Combinations of 3'-azido-3'-deoxythymidine (zidovudine) and phosphonoformate (foscarnet) against human immunodeficiency virus type 1 and cytomegalovirus replication in vitro

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

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