Abstract:  Background:  Valganciclovir prophylaxis is reportedly associated with a low incidence of ganciclovir‐resistant cytomegalovirus (CMV). We assessed the incidence, clinical features, and outcome of drug‐resistant CMV among solid organ transplant patients who received valganciclovir prophylaxis.

Methods:  The medical records of all CMV D+/R− kidney, pancreas, liver, and heart recipients were screened for CMV disease, and the clinical course and outcomes of patients with drug‐resistant CMV were reviewed.

Results:  During a four‐yr‐study period, a total of 225 CMV D+/R− transplant patients received valganciclovir prophylaxis for a median of 92 d. Sixty‐five (29%) of the 225 patients developed delayed‐onset primary CMV disease, including nine (14%) suspected to have drug‐resistant virus. Four (6.2%) had confirmed UL97 or UL54 mutations. All except one patient manifested gastrointestinal tissue‐invasive disease. Together with reduction in immunosuppression, intravenous foscarnet with or without CMV hyperimmunoglobulin was the most common treatment. Drug‐associated nephrotoxicity was commonly observed and resulted in allograft loss in two patients. During the mean follow‐up of 2.2 yr, allograft loss and mortality occurred in two of four patients with proven and in three of five patients with clinically suspected drug‐resistant CMV.

Conclusions:  Cytomegalovirus disease because of clinically suspected or genotypically confirmed drug‐resistant CMV is not uncommon in CMV D+/R− solid organ transplant patients who received valganciclovir prophylaxis. Because of its significant morbidity and mortality, an optimized strategy of CMV prevention is warranted to reduce the negative impact of drug‐resistant CMV on the successful outcome of organ transplantation.