Case report Viral monitoring and successful treatment of a ganciclovir-resistant cytomegalovirus infection in a heart transplant recipient J.Garcı´a-Martı´nez 1 , L. Folgueira 1 , R. Delgado 1 , S. Hernando 1 , C. Prieto 1 , J.M. Aguado 2 , J.R. Otero 1 1 Department of Microbiology, 2 Infectious Diseases Unit, Hospital Universitario 12 de Octubre, Madrid, Spain J. Garc|¤ a-Mart|¤ nez, L. Folgueira, R. Delgado, S. Hernando, C. Prieto, J.M. Aguado, J.R. Otero.V|ral monitoring and successful treatment of a ganciclovir-resistant cytomegalovirus infection in a heart transplant recipient. Transpl Infect Dis 2008: 10: 123^128. All rights reserved Abstract: We reported a ganciclovir (GCV)-resistant cytomegalovirus (CMV) infection in a heart transplant recipient. Genotypic and phenotypic susceptibility assays demonstrated an A594Vmutation in the UL97 phosphotransferase gene and GCV IC 50 496 mM. Low GCV concentration exposure, immunosuppressive treatment, donor- positive/recipient-negative CMVserostatus, viral reactivations within antiviral prophylaxis or treatment, contributed to GCV-resistant strain selection.                                                                                   Cytomegalovirus (CMV) infection continues to be an im- portant complication in bone marrow (1) and solid organ transplant recipients (2). The appropriate management of these patients depends on (a) the identi¢cation of those at highest risk, (b) an early diagnosis, and (c) monitoring of the antiviral treatment response (3). This monitoring has been possible through the CMV pp65 antigenemia assays (4) and, more recently, using real-time polymerase chain re- action (PCR)-based quantitative methods (3). The selection of antiviral-resistant strains is an added complication. Ganciclovir (GCV)-resistant CMV infections have been described since 1986 in both human immunode- ¢ciency virus-seropositive patients (5) and transplant re- cipients (6). GCV resistance is mainly due to point mutations that tend to accumulate within UL97 phospho- transferase and DNA polymerase genes (7), but emergence and selection of GCV-resistant CMV strains have usually been associated with CMV-seronegative recipients who have received a graft from a CMV-seropositive donor (D 1 /R À ), long-term or subtherapeutic GCVexposure, and immunosuppressive therapies (8). We herein present a GCV-resistant CMV infection in a heart transplant recipient, the contributing factors, and the viral monitoring of the process. Case report A 37-year-old woman, CMV seronegative before transplan- tation, received a cardiac graft from a CMV-seropositive do- nor. After an early heart failure, because of humoral and cellular rejection, she received OKT3 treatment for 14 days; steroids, azathioprine, cyclosporine, and a GCV (6 mg/kg/ day intravenously [IV]) prophylaxis regimen were also ad- ministered. On day 1 30 post transplantation, and after a new graft rejection episode, treatment with tacrolimus (FK- 500), mycophenolate mofetil, and steroids was implement- ed, while cyclosporine and azathioprine regimens were dis- continued. On day 1 61, the patient suffered from her ¢rst viral syn- drome: leukothrombopenia, fever 4381C, transaminase Copyright r Blackwell Munksgaard 2007 Transplant Infectious Disease . ISSN 1398-2273 Key words: ganciclovir; cytomegalovirus; heart transplant; foscarnet; UL97 phosphotransferase Correspondence to: Jesu ´s Garcı ´a-Martinez, Department of Microbiology, Hospital de Fuenlabrada, Co Molino, 2. 28942 Fuenlabrada, Madrid, Spain Tel: 1 34 91 600 6424 Fax: 1 34 91 565 27 65 E-mail: jgarciam.hflr@salud.madrid.org Received 21 March 2006, revised 13 July, 19 October 2006, 21 January 2007, accepted for publication 14 February 2007 DOI: 10.1111/j.1399-3062.2007.00243.x Transpl Infect Dis 2008: 10: 123–128 123