Emergence of ganciclovir-resistant cytomegalovirus disease among recipients of solid-organ transplants

Background Concerns have been raised about emergence of ganciclovir resista nce as a result of the advent of both routine oral ganciclovir prophylaxis and highly potent immunosuppression. We retrospectively assessed the occurr ence of ganciclovir-resistant cytomegalovirus disease among transplant reci pients who had received oral ganciclovir prophylaxis and highly potent immu nosuppression, Methods We studied 240 recipients of liver, kidney, or pancreas transplants . Antiviral susceptibility testing of blood cytomegaloviral isolates was do ne when patients failed to respond to intravenous ganciclovir treatment for symptomatic cytomegalovirus infection. Portions of the UL97 gene associate d with ganciclovir resistance were sequenced in cytomegalovirus isolates wi th phenotypic resistance to ganciclovir. Findings Ganciclovir-resistant cytomegalovirus disease developed in five (7 %) of 67 seronegative recipients of cytomegalovirus-seropositive organs (D/R-) com pared with none of 173 seropositive recipients (p=0.002). Among th e 25 (10.4%) patients who developed cytomegalovirus disease within 1 year a fter transplantation, five had ganciclovir-resistant cytomegalovirus diseas e. Among D+/R-transplant recipients, ganciclovir-resistant cytomegalovirus disease was more common among the group receiving the most potent immunosup pression-ie, recipients of kidney and pancreas or pancreas alone (four of 1 9) compared with all other transplant recipients tone of 48, p=0.02). Ganci clovir-resistant cytomegalovirus disease was diagnosed at a median of 10 mo nths after transplantation (range 7-12) after lengthened exposure to gancic lovir, was associated with previously described mutations of the UL97 gene, and led to serious clinical complications. Interpretation Ganciclovir-resistant cytomegalovirus is an important cause of late morbidity among D+/R- transplant recipients who have had lengthened exposure to ganciclovir and have received highly potent immunosuppression. Strategies to reduce this complication, especially among D+/R- patients, a re warranted.