Emergence of drug-resistant cytomegalovirus in the era of valganciclovir prophylaxis: therapeutic implications and outcomes

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.