Letter to the Editor Ganciclovir-resistant cytomegalovirus infection in transplanted patients: utility of drug monitoring P. Esposito, G. Bedino, F. Montagna, M. Gregorini, T. Rampino, A. Dal Canton. Ganciclovir-resistant cytomegalovirus infection in transplanted patients: utility of drug monitoring. Transpl Infect Dis 2013: 15: E122–E123. All rights reserved P. Esposito, G. Bedino, F. Montagna, M. Gregorini, T. Rampino, A. Dal Canton Department of Nephrology, Dialysis and Transplantation, Fondazione IRCCS Policlinico San Matteo and University of Pavia, Pavia, Italy Key words: CMV infection; cytomegalovirus; transplantation; ganciclovir; drug resistance; therapeutic drug monitoring Correspondence to: Pasquale Esposito, Department of Nephrology, Dialysis and Transplantation, Fondazione Policlinico S.Matteo, Pavia, Italy, Piazzale Golgi 19, Pavia 27100, Italy Tel/Fax: +3 90 382 503 883 E-mail: pasqualeesposito@hotmail.com Received 7 December 2012, revised 11 December 2012, accepted for publication 23 December 2012 DOI: 10.1111/tid.12078 Transpl Infect Dis 2013: 15: E122–E123 To the Editor We read with great interest the paper by Kim et al. (1), recently published in Transplant Infectious Disease. The authors evaluated the clinical impact of ganciclovir (GCV)-resistant cytomegalovirus (CMV) infection caused by UL97 mutations in pediatric patients undergoing hematopoietic cell and solid organ transplantation. Among 89 transplant recipients presenting CMV viremia, 7 subjects considered to be GCV-resistant were tested for UL97 mutations, detecting the pres- ence of major mutations in 2 cases. The clinical course of these 2 patients was particularly severe, being characterized by a complicated CMV disease that required multiple-drug therapy and resulted, in 1 case, in death from disseminated CMV infection. Therefore, the authors concluded that evaluation of gene mutations should be considered when resistant CMV infection is suspected. We agree with this suggestion, which is also in line with that recommended by International Consensus Guidelines released by the Transplantation Society (2), but we think that other aspects are also notewor- thy. In their paper, the authors, when evaluating GCV-resistant patients, did not consider the possibility that drug treatment with GCV could have been insuffi- cient, and no data on plasma GCV levels have been reported. In fact, it should be underlined that resis- tance of CMV to antiviral drugs, which in most cases has been attributed to viral mutations of UL97 and UL57 genes (3), may also be associated with the use of subtherapeutic levels of the drug, instead of a genetic CMV mutation (4). Recently, we reported a case of an adult kidney transplant recipient who, early after transplantation, experienced a life-threatening systemic CMV infec- tion, which was resistant to standard GCV therapy (5). The lack of responsiveness to the therapy, associ- ated with the rising viral loads (up to 11,347,000 copies/mL) and progressive disease, led us to suspect the occurrence of a CMV resistance to GCV. So, we E122 © 2013 John Wiley & Sons A/S Transplant Infectious Disease, ISSN 1398-2273