The use of sirolimus in ganciclovir‐resistant cytomegalovirus infections in renal transplant recipients

Ozaki, Kikumi S.; Câmara, Niels Olsen Saraiva; Nogueira, Eliana; Pereira, Maurício Galvão; Granato, Celso Francisco Hernandes; Melaragno, Cláudio S.; Camargo, Luís Fernando Aranha; Pacheco-Silva, Álvaro

doi:10.1111/j.1399-0012.2007.00699.x

Cited by 63 publications

(44 citation statements)

References 20 publications

(24 reference statements)

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“…The occurrence of primary infection (CMV IgG serostatus; D+/R−) and the therapy of acute rejection have also been shown to predict CMV disease outcome (21)(22)(23). Thus, the intensity of the immunosuppressive therapy may influence the treatment of CMV Å sberg et al (24)(25)(26) and mTOR inhibitors may have direct anti-CMV effects (9,27,28 (17), and we have reported previously specific risk factors for recurrence and long-term outcomes in this study (29) (17). Effect of Immunosuppressive Therapy on CMV (Figure 2), also show significantly higher rates of (17,29).…”

Section: Cytomegalovirus (Cmv) Disease Is a Common Clinical Infectionmentioning

confidence: 99%

Effects of the Intensity of Immunosuppressive Therapy on Outcome of Treatment for CMV Disease in Organ Transplant Recipients

Åsberg

Jardine

Bignamini

et al. 2010

American Journal of Transplantation

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Section: Cytomegalovirus (Cmv) Disease Is a Common Clinical Infectionmentioning

confidence: 99%

Effects of the Intensity of Immunosuppressive Therapy on Outcome of Treatment for CMV Disease in Organ Transplant Recipients

Åsberg

Jardine

Bignamini

et al. 2010

American Journal of Transplantation

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“…Sirolimus has antiviral properties and conveys a lower risk of CMV disease (24)(25)(26)(27); one prospective study of 1470 renal transplant recipients (55 of whom were kidney-pancreas transplant recipients) found that the use of sirolimus had a protective effect against CMV disease (odds ratio 0.27) (24), the Symphony trial also found a much lower rate of CMV in those on low dose sirolimus (6%) compared with those on standard or low cyclosporine Kotton A (15% and 11%) ([p = 0.003]) (28), and another trial noted that everolimus conveyed a reduction in the incidence of CMV infection, syndrome and viremia in de novo renal transplant recipients (29).…”

Section: Universal Prophylaxis and Preemptive Therapymentioning

confidence: 99%

CMV: Prevention, Diagnosis and Therapy

Kotton

2013

American Journal of Transplantation

242

218

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Cytomegalovirus (CMV) is the most common infection after organ transplantation and has a major impact on morbidity, mortality and graft survival. Optimal prevention, diagnosis and treatment of active CMV infection enhance transplant outcomes, and are the focus of this section. Methods to prevent CMV include universal prophylaxis and preemptive therapy; each has its merits, and will be compared and contrasted. Diagnostics have improved substantially in recent years, both in type and quality, allowing for more accurate and savvy treatment; advances in diagnostics include the development of an international standard, which should allow comparison of results across different methodologies, and assays for cellular immune function against CMV. Therapy primarily involves ganciclovir, now rendered more versatile by data suggesting oral therapy with valganciclovir is not inferior to intravenous therapy with ganciclovir. Treatment of resistant virus remains problematic, but is enhanced by the availability of multiple novel therapeutic agents.

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“…Leflunomide alone or in combination with standard antiviral agents has shown some efficacy in transplant recipients refractory to current therapy (Avery et al 2010;Dunn et al 2013;Verkaik et al 2013). The combination of GCV and the immunosuppressive agent sirolimus for the treatment of GCV-resistant HCMV infections has led to a favorable outcome with respect to clinical status and graft rejection in kidney and kidney-pancreas recipients (Ozaki et al 2007). …”

Section: Management Of Infections Caused By Drug-resistant Hcmv Mutantsmentioning

confidence: 97%

Antiviral Drug Resistance in Herpesviruses

Piret

Drouot

Boivin

2014

Handbook of Antimicrobial Resistance

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The discovery of acyclovir (ACV), a nucleoside analogue, more than 30 years ago, represents a milestone in the management of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections. The modest activity of ACV against human cytomegalovirus (HCMV) has prompted the development of another nucleoside analogue, ganciclovir (GCV), for the management of systemic and organ-specific HCMV diseases. Second-line agents such as the pyrophosphate analogue foscarnet (FOS) and the nucleotide analogue cidofovir (CDV) have been approved subsequently. In contrast to ACV and GCV, the latter drugs do not require an initial phosphorylation step by viral protein kinases to be converted into their active forms. Since the introduction of these antivirals, the emergence of drug-resistant mutants has been constantly reported particularly in severely immunocompromised patients such as bone marrow and solid organ transplant recipients as well as human immunodeficiency virus (HIV)-infected individuals. In this chapter, we review the characteristics of the antiviral agents currently approved for the management of HSV, VZV, and HCMV diseases, the laboratory methods for assessing drug susceptibilities, and the clinical significance of drug-resistant infections and their management.

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The use of sirolimus in ganciclovir‐resistant cytomegalovirus infections in renal transplant recipients

Abstract: This suggests that the use of sirolimus plus ganciclovir therapy could be useful in ganciclovir-resistant CMV infections.

Cited by 63 publications

References 20 publications

Effects of the Intensity of Immunosuppressive Therapy on Outcome of Treatment for CMV Disease in Organ Transplant Recipients

Effects of the Intensity of Immunosuppressive Therapy on Outcome of Treatment for CMV Disease in Organ Transplant Recipients

CMV: Prevention, Diagnosis and Therapy

Antiviral Drug Resistance in Herpesviruses

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