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Cytomegalovirus infection and ganciclovir resistance caused by UL 97 mutations in pediatric transplant recipients
Author(s) -
Kim Y.J.,
Boeckh M.,
Cook L.,
Stempel H.,
Jerome K.R.,
Boucek R.,
Burroughs L.,
Englund J.A.
Publication year - 2012
Publication title -
transplant infectious disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.69
H-Index - 67
eISSN - 1399-3062
pISSN - 1398-2273
DOI - 10.1111/j.1399-3062.2012.00760.x
Subject(s) - medicine , ganciclovir , viremia , cytomegalovirus , transplantation , foscarnet , hematopoietic stem cell transplantation , immunology , gastroenterology , human cytomegalovirus , herpesviridae , viral disease , virus
Background Cytomegalovirus ( CMV ) infection may cause serious disease after hematopoietic cell transplantation ( HCT ) and solid organ transplantation ( SOT ), but few reports describe ganciclovir ( GCV ) resistance in pediatric patients. Objectives This study was performed to describe the clinical impact of CMV infection with UL 97 mutation in pediatric transplant recipients. Methods Quantitative surveillance data for CMV infection in pediatric patients between O ctober 2001 and F ebruary 2007 at the U niversity of W ashington were analyzed. Testing for UL 97 mutation was performed in selected patients with prolonged CMV viremia despite therapy. Data associated with the detection of UL 97 mutations were reviewed. Results CMV was detected in 89 pediatric transplant recipients. Among these, 39 had undergone HCT and 50 SOT (12 heart, 22 kidney, 15 liver, and 1 bilateral lung transplants). CMV with at least one UL 97 sequence variation was detected in 5 patients: 4 HCT recipients (4/39, 10%) and 1 heart transplant recipient (1/50, 2%). All 5 pediatric patients were CMV seropositive before transplantation. Underlying conditions included chronic myelogenous leukemia, primary immunodeficiency disorders, and hypoplastic left heart syndrome. One known GCV drug‐resistant mutation was detected in 2 HCT recipients (A594V). Three strain variants with mutations considered to have no significant impact on UL 97 function (H469Y, N510S, and D605E) were detected. Two of these 5 patients died, 1 because of uncontrolled CMV infection and 1 with other complications. Conclusions UL 97 drug‐resistant mutations occur in pediatric transplant recipients with CMV viremia and can cause serious disease. Screening for mutations conferring resistance to CMV antivirals should be considered for patients with persistent viremia during therapy and the sequences of UL 97 mutations evaluated.