Introduction: CMV infection is one of the more frequent infection after solid organ transplantation. Several specific antiviral therapy are nowadays available with success in most cases.

Methods: A 38 years old woman underwent total enterectomy due to severe tertiary peritonitis with multiple intestinal perforation. In may 2016 she undewent multivisceral and abdominal wall transplantation from the same donor. She underwent regular antibiotic, antifungal and antiviral profilaxis as universally described. Her CMV serological status wasD+/R+.

Results: During post operative course a severe abdominal wall infection occurred and vacuum assisted closure needed to avoide abdominal wall graft removal. Despite minimization of the immunosuppressive regimen due to severe abdominal infection and despite antiviral profilaxis, in july 2016 the patient developed a CMV reactivation. Ganciclovir treatment was unsuccessfully attempted and a drug resistence test showed M460V mutation on UL97 gene which gives ganciclovir/valganciclovir resistence. Foscarnet treatment was tried,initially successfully, then CMV viremia increased again. A new drug test resistence showed a viral strain with multiple mutations: M460V on UL97 gene (as the previous test), Q578H and E756D on UL54 gene to confer a pan-drug-resistence (PDR) profile towards all drugs anti CMV available (ganciclovir,valganciclovir,foscarnet,cidofovir). Meanwhile the patient developed CMV disease with intestinal and retinal involvement. After multidisciplinary discussion and literature review,a rescue treatment with leflunomide was started. This is a rheumatoid and psoriatic arthritis drug with known anti CMV activity. With the combination of leflunomide and anti CMV immonoglobulins we obtained a complete response of CMV viremia. Leflunomide was discontinued after 1 year of treatment (due to lower limbs side effects) and anti CMV specific immunoglobulins was continued with progressive dosage descalation.

Conclusion: Leflunomide can be considered a rescue therapy in the cases of pan drug resistant CMV infection. The patient is nowadays stil alive,with residual blindness but with functioning graft,without parenteral or fluid support and with constantly negative cmv viremia.