Cytomegalovirus infection and ganciclovir resistance caused by <scp>UL</scp>97 mutations in pediatric transplant recipients

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Cytomegalovirus (<jats:styled-content style="fixed-case">CMV</jats:styled-content>) infection may cause serious disease after hematopoietic cell transplantation (<jats:styled-content style="fixed-case">HCT</jats:styled-content>) and solid organ transplantation (<jats:styled-content style="fixed-case">SOT</jats:styled-content>), but few reports describe ganciclovir (<jats:styled-content style="fixed-case">GCV</jats:styled-content>) resistance in pediatric patients.</jats:p></jats:sec><jats:sec><jats:title>Objectives</jats:title><jats:p>This study was performed to describe the clinical impact of <jats:styled-content style="fixed-case">CMV</jats:styled-content> infection with <jats:styled-content style="fixed-case">UL</jats:styled-content>97 mutation in pediatric transplant recipients.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Quantitative surveillance data for <jats:styled-content style="fixed-case">CMV</jats:styled-content> infection in pediatric patients between <jats:styled-content style="fixed-case">O</jats:styled-content>ctober 2001 and <jats:styled-content style="fixed-case">F</jats:styled-content>ebruary 2007 at the <jats:styled-content style="fixed-case">U</jats:styled-content>niversity of <jats:styled-content style="fixed-case">W</jats:styled-content>ashington were analyzed. Testing for <jats:styled-content style="fixed-case">UL</jats:styled-content>97 mutation was performed in selected patients with prolonged <jats:styled-content style="fixed-case">CMV</jats:styled-content> viremia despite therapy. Data associated with the detection of <jats:styled-content style="fixed-case">UL</jats:styled-content>97 mutations were reviewed.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> <jats:styled-content style="fixed-case">CMV</jats:styled-content> was detected in 89 pediatric transplant recipients. Among these, 39 had undergone <jats:styled-content style="fixed-case">HCT</jats:styled-content> and 50 <jats:styled-content style="fixed-case">SOT</jats:styled-content> (12 heart, 22 kidney, 15 liver, and 1 bilateral lung transplants). <jats:styled-content style="fixed-case">CMV</jats:styled-content> with at least one <jats:styled-content style="fixed-case">UL</jats:styled-content>97 sequence variation was detected in 5 patients: 4 <jats:styled-content style="fixed-case">HCT</jats:styled-content> recipients (4/39, 10%) and 1 heart transplant recipient (1/50, 2%). All 5 pediatric patients were <jats:styled-content style="fixed-case">CMV</jats:styled-content> seropositive before transplantation. Underlying conditions included chronic myelogenous leukemia, primary immunodeficiency disorders, and hypoplastic left heart syndrome. One known <jats:styled-content style="fixed-case">GCV</jats:styled-content> drug‐resistant mutation was detected in 2 <jats:styled-content style="fixed-case">HCT</jats:styled-content> recipients (A594V). Three strain variants with mutations considered to have no significant impact on <jats:styled-content style="fixed-case">UL</jats:styled-content>97 function (H469Y, N510S, and D605E) were detected. Two of these 5 patients died, 1 because of uncontrolled <jats:styled-content style="fixed-case">CMV</jats:styled-content> infection and 1 with other complications.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p> <jats:styled-content style="fixed-case">UL</jats:styled-content>97 drug‐resistant mutations occur in pediatric transplant recipients with <jats:styled-content style="fixed-case">CMV</jats:styled-content> viremia and can cause serious disease. Screening for mutations conferring resistance to <jats:styled-content style="fixed-case">CMV</jats:styled-content> antivirals should be considered for patients with persistent viremia during therapy and the sequences of <jats:styled-content style="fixed-case">UL</jats:styled-content>97 mutations evaluated.</jats:p></jats:sec>