4CPS-250 Experience of tecovirimat and cidofovir use in a patient with monkeypox: a case report
Lupe Rodríguez-de FranciscoAB Guisado-GilMarta Mejías-TruebaLaura Herrera‐HidalgoSantiago José Lora-EscobarRafael Luque‐MárquezMV Gil-Navarro
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Abstract:
Background and Importance
Current treatment for Monkeypox's disease (MPXV) is mainly symptomatic. However, in immunocompromised patients, hospitalisation and treatment with antiviral drugs may be necessary. With the recent outbreak of MPXV, new strategies have been proposed.Aim and Objectives
The aim of the study was to describe our clinical experience with tecovirimat and cidofovir in the treatment of MPXV in a patient whose CD4+ lymphocyte level is less than 50 cells/ml.Material and Methods
The effectiveness of tecovirimat-cidofovir was assessed by the evolution of the rash from macule to crusts that dry up and fall off.Results
The patient was a 35-year-old man diagnosed with MPXV who presented skin lesions in the perineal area, extremities, face, trunk and back and severe proctitis. At admission, the patient was diagnosed with HIV (severely immunosuppressed with CD4+ lymphocyte levels of <40 cells/ml), so he was started on antiretroviral treatment (BIC/TAF/TDF). Sexually transmitted infection screening detected Chlamydia trachomatis infection, which was treated with doxycycline. In the context of MPXV proctitis, it was decided to apply for tecovirimat, the antiviral treatment of choice. The dosage for tecovirimat is weight-based, 600 mg was administered every 12 hours for 14 days (30/08/22–12/09/22). Regarding effectiveness, no new lesions were observed and those already present were regressing, except in the perianal area, where the lesions continued to progress. Therefore, it was decided to administer intravenous cidofovir 5 mg/kg twice weekly (09/09/22, 16/09/22). To avoid toxicity, oral probenecid was administered concomitantly: 2 g 3 hours before and 1 g 2 and 8 hours after completing the perfusion, in addition to 0.9% saline solution 1000 ml 1 h before. After the treatment, there was a progression of lesions in the right inguinal region, palpating left inguinal adenopathy and intense involvement of the testicle, groin and perineal area.Conclusion and Relevance
In contrast to previous cases of patients whose CD4+ lymphocyte levels were above 500 cells/ml, the treatment with tecovirimat and cidofovir in this patient did not achieve a satisfactory response due to the continuous appearance of new lesions. The severe immunosuppression could probably explain the aggressive development of the disease.References and/or Acknowledgements
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Cidofovir
To assess the potential benefit of intralesional administration of cidofovir, an acyclic nucleoside phosphonate with activity against several DNA viruses, for treating severe respiratory papillomas in pediatric patients.Prospective case series.Tertiary care children's hospitals.Five pediatric patients with severe recurrent respiratory papillomatosis requiring laryngoscopy with carbon dioxide laser therapy more frequently than once a month to maintain airway patency. Each patient underwent between 12 and 33 laryngoscopies with laser treatment prior to being injected with cidofovir.Microsuspension laryngoscopy with intralesional injection of cidofovir (Vistide) in conjunction with mechanical debulking and carbon dioxide laser of papillomas.Papilloma stage at time of serial laryngoscopies.One patient was disease free and 3 patients demonstrated a dramatic response to adjuvant therapy with cidofovir at the 9-month follow-up visit after the last injection of cidofovir. One patient showed an improvement in papilloma stage that was possibly related to concurrent therapy with interferon.Intralesional injection of cidofovir seems to be of benefit in the treatment of severe respiratory papillomatosis in pediatric patients. Larger prospective studies with longer follow-up will be required before cidofovir can be considered an accepted means of managing this difficult disease.
Cidofovir
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BACKGROUND:Progressive multifocal leukoencephalopathy (PML) is a subacute demyelinating illness caused by the JC virus, a polyomavirus that occurs in 4–5% of HIV-positive patients. Mortality is high, and no useful therapy has been identified. Highly active antiretroviral therapy (HAART) has been reported to be effective in halting progression of the disease in some, but not all, patients. Cidofovir has been shown to be active against polyomaviruses.OBJECTIVE:To review data on the use of cidofovir to treat PML.DATA SOURCES:English-language case reports and clinical studies were located through a literature search (MEDLINE and AIDSLINE, 1995–July 2000).STUDY SELECTION AND DATA EXTRACTION:Relevant case reports and studies describing the use of cidofovir for PML were reviewed.DATA SYNTHESIS:Most case reports describing the use of cidofovir have shown that the drug is effective in the treatment of PML. Some patients were also receiving HAART concurrently; therefore, it is not clear which treatment modality had a greater impact on PML. However, cidofovir may be effective in patients whose disease has progressed despite HAART or who are unable to tolerate these regimens. A pilot study of cidofovir for treating PML has completed enrollment, but preliminary results showed no benefit.CONCLUSIONS:Cidofovir may be the most reasonable treatment option for PML in HIV-infected individuals who fail to improve with HAART or who are unable to tolerate these regimens. Patients who receive cidofovir should be monitored for renal and ocular toxicity.
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Cidofovir is a nucleotide analog marketed for the treatment of human cytomegalovirus infections in immunocompromised patients. An increasing number of reports have appeared on the use of cidofovir for the treatment of other severe DNA virus infections in immunocompromised patients. The activity of cidofovir against herpes simplex viruses resistant to classic (acyclovir and/or foscavir) therapy has been widely documented. Cidofovir has also been used for the treatment of other herpesvirus infections, such as drug-resistant varicella-zoster virus, and Epstein-Barr virus-induced proliferative diseases. For papillomavirus infections, cidofovir represents a valuable alternative to the conventional therapies, which are mostly based on surgery, as in the treatment of laryngeal papillomatosis. The role of cidofovir in the treatment of polyomavirus infections is more controversial, but here too, cidofovir represents, to date, the only available efficacious therapeutic modality. Cidofovir has demonstrated activity against all poxviruses and represents a unique therapeutic modality for use against these viruses, particularly in the immunosuppressed host, should this prove necessary (eg, in a bioterrorism scenario).
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Abstract Recurrent respiratory papillomatosis (RRP) is a chronic and difficult to treat disease of the larynx. In 1998, the first article was published that described the use of the antiviral substance cidofovir to treat this disease. Although the results are promising, there remains some concern about the potential carcinogenicity of cidofovir. There is a demand for a qualitative review of the side-effects of this medicine. In this review, the side-effects of cidofovir are investigated. Special attention was given to the potential carcinogenicity of cidofovir. For this review a search is performed in PubMed and EMBASE for relevant articles in which the use of intralesional cidofovir for patients with RRP is described. Eventually, 31 articles could be included for this review. In these articles a total of 188 patients with RRP were described who underwent therapy with intralesional cidofovir. Five of these patients have developed dysplasia of the larynx during the treatment with cidofovir. This is a percentage of 2.7. This percentage is concurrent with the incidence of spontaneous malignant degeneration of RRP (2–3%). Based on this review, it can be concluded that the use of intralesional cidofovir does not increase the risk of laryngeal dysplasia. Apart from the articles that describe the intralesional administration of cidofovir, some articles have been published in which the use of intravenous cidofovir is described as a therapy for RRP. Therefore, a summary is given on the side-effects of intralesional cidofovir as well as a summary on the reported side-effects of the intravenous administration of cidofovir. Based on the outcomes of this review, recommendations are given for a safe use of cidofovir for treatment of recurrent respiratory papillomatosis in the future.
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Cidofovir is a potent nucleoside analog antiviral drug approved for the treatment of cytomegalovirus (CMV) retinitis in patients with the Acquired Immune Deficiency Syndrome (AIDS). It is currently available only for intravenous infusion. Several small studies and case reports describe the successful use of cidofovir applied either topically or by intralesional injection in several virally induced cutaneous diseases. Available information demonstrates that cidofovir is a potent antiviral agent with activity against several DNA viruses that cause cutaneous disease when applied topically or administered by intralesional injection. No significant systemic side effects have been noted, although application site reactions are common and can occasionally be severe. The effective use of topical and intralesional cidofovir for the treatment of diseases of the skin caused by DNA viruses has been demonstrated in animals and a limited number of patients including those infected with human immunodeficiency virus (HIV). This article reviews the pharmacology of cidofovir and the utility of topical and intralesional cidofovir for the treatment of viral infections caused by human papillomavirus, herpesviruses (including acyclovir resistant strains), Kaposi's sarcoma-associated herpesvirus, molluscum contagiosum and monkeypox.
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