Treatment of multidrug‐resistant cytomegalovirus retinitis with systemically administered leflunomide

Abstract

Multiresistant cytomegalovirus (CMV) infection is increasingly recognized in solid organ transplant recipients. Leflunomide is a novel drug with both immunosuppressive and anti-CMV properties. Herein we report a case of a renal transplant recipient treated with leflunomide for multiresistant CMV retinitis, and provide correlation between serum and vitreous levels of leflunomide. She had stabilization of her retinitis and measurable levels of drug in her vitreous fluid and serum. These initial findings suggest that leflunomide may be useful in the treatment of CMV disease, including retinitis in patients after solid organ transplantation.

Multidrug-resistant cytomegalovirus infection in a pediatric stem cell transplantation patient

“…At this point, no approved therapeutic options for CMV disease were available and unfortunately, no access to compassionate use of novel anti-CMV drugs under clinical development was available. Although a few reports have described the use of leflunomide for therapy of multidrug-resistance CMV disease (Avery et al, 2004;Levi et al, 2006;Verkaik et al, 2013;Dunn et al, 2013), treatment with this drug having both immunosuppressive and anti-CMV properties was not envisaged in our patient.…”

Multidrug Resistance Conferred by Novel DNA Polymerase Mutations in Human Cytomegalovirus Isolates

“…Previously reported DNA polymerase mutations (N408K, L737M, and A834P) were identified in EDTA-anticoagulated blood specimens from patients with clinical evidence of infection with antiviral-resistant CMV (30,39). These specimens were obtained with patient consent, and testing was carried out following the ethical guidelines of the South Eastern Sydney and Illawarra Area Health Service.…”

“…Two of these, N408K (which occurs in DNA polymerase domain IV) and A834P (which occurs in DNA polymerase domain III), were identified in separate Dϩ/RϪ lung transplant recipients from Australia and in a kidney transplant recipient from the United States. None of the patients responded to GCV, FOS, or CDV therapy (30,39). The third mutation, L737M (DNA polymerase domain II), was identified in a liver transplant recipient receiving GCV (39).…”

Characterization of Multiple Cytomegalovirus Drug Resistance Mutations Detected in a Hematopoietic Stem Cell Transplant Recipient by Recombinant Phenotyping

“…In general, UL54 mutations emerge after prolonged GCV exposure and thereby increase the level of GCV resistance conferred by mutations already present in the UL97 gene (6)(7)(8)(9). Infections with multidrug-resistant CMV isolates that contain several mutations in the UL97 and/or UL54 genes were reported in immunocompromised patients (10)(11)(12). Such CMV infections may be associated with a single isolate that harbors multiple mutations in the UL97 and/or UL54 genes or may result from mixed virus subpopulations that harbor different mutations (6).…”