{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T21:01:06Z","timestamp":1760821266892,"version":"3.37.3"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,9,23]],"date-time":"2021-09-23T00:00:00Z","timestamp":1632355200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,9,23]],"date-time":"2021-09-23T00:00:00Z","timestamp":1632355200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100007365","name":"Fondazione IRCCS Policlinico San Matteo","doi-asserted-by":"publisher","award":["80207"],"award-info":[{"award-number":["80207"]}],"id":[{"id":"10.13039\/100007365","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Infect Dis"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Human Cytomegalovirus (HCMV) still represents a crucial concern in solid organ transplant recipients (SOTRs) and the use of antiviral therapy are limited by side effects and the selection of viral mutations conferring antiviral drug resistance.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Case presentation<\/jats:title>\n                <jats:p>Here we reported the case of an HCMV seronegative patient with common variable immunodeficiency (CVID), multiple hepatic adenomatosis, hepatopulmonary syndrome and portal hypertension who received a liver transplant from an HCMV seropositive donor.\u00a0The patient was treated with Valganciclovir (vGCV) and then IV Ganciclovir (GCV) at 5 week post-transplant for uncontrolled HCMV DNAemia. However, since mutation A594V in UL97 gene conferring resistance to ganciclovir was reported, GCV therapy was interrupted.\u00a0Due to the high toxicity of Foscarnet (FOS) and Cidofovir (CDV), Letermovir (LMV) monotherapy at the dosage of 480\u00a0mg per day was administered, with a gradual viral load reduction. However, a relapse of HCMV DNAemia revealed the presence of mutation C325Y in HCMV UL56 gene conferring resistance to LMV.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>In conclusion, even if LMV is an effective and favorable safety molecule it might have a lower genetic barrier to resistance. A warning on the use of LMV monotherapy as rescue treatments for HCMV GCV-resistant infections in transplant recipients is warranted.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12879-021-06694-4","type":"journal-article","created":{"date-parts":[[2021,9,23]],"date-time":"2021-09-23T23:05:23Z","timestamp":1632438323000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Emergence of Letermovir-resistant HCMV UL56 mutant during rescue treatment in a liver transplant recipient with ganciclovir-resistant infection HCMV: a case report"],"prefix":"10.1186","volume":"21","author":[{"given":"Stefania","family":"Paolucci","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Campanini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene","family":"Cassaniti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Tebaldi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Novazzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alice","family":"Fratini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonella","family":"Meini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Girelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Palumbo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Plebani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fausto","family":"Baldanti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,9,23]]},"reference":[{"issue":"4","key":"6694_CR1","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1128\/CMR.00009-10","volume":"23","author":"NS Lurain","year":"2010","unstructured":"Lurain NS, Chou S. Antiviral drug resistance of human cytomegalovirus. Clin Microbiol Rev. 2010;23(4):689\u2013712.","journal-title":"Clin Microbiol Rev"},{"issue":"10","key":"6694_CR2","doi-asserted-by":"publisher","first-page":"e74","DOI":"10.1097\/TP.0000000000001418","volume":"100","author":"RK Avery","year":"2016","unstructured":"Avery RK, Arav-Boger R, Marr KA, Kraus E, Shoham S, Lees L, Trollinger B, Shah P, Ambinder R, Neofytos D, Ostrander D, Forman M, Valsamakis A. Outcomes in transplant recipients treated with foscarnet for ganciclovir-resistant or refractory cytomegalovirus infection. Transplantation. 2016;100(10):e74-80. https:\/\/doi.org\/10.1097\/TP.0000000000001418.","journal-title":"Transplantation."},{"issue":"1","key":"6694_CR3","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1128\/AAC.00561-13","volume":"58","author":"LR Minces","year":"2014","unstructured":"Minces LR, Nguyen MH, Mitsani D, Shields RK, Kwak EJ, Silveira FP, Abdel-Massih R, Pilewski JM, Crespo MM, Bermudez C, Bhama JK, Toyoda Y, Clancy CJ. Ganciclovir-resistant cytomegalovirus infections among lung transplant recipients are associated with poor outcomes despite treatment with foscarnet-containing regimens. Antimicrob Agents Chemother. 2014;58(1):128\u201335.","journal-title":"Antimicrob Agents Chemother."},{"issue":"20","key":"6694_CR4","doi-asserted-by":"publisher","first-page":"10884","DOI":"10.1128\/JVI.05265-11","volume":"85","author":"T Goldner","year":"2011","unstructured":"Goldner T, Hewlett G, Ettischer N, Ruebsamen-Schaeff H, Zimmermann H, Lischka P. The novel anticytomegalovirus compound AIC246 (Letermovir) inhibits human cytomegalovirus replication through a specific antiviral mechanism that involves the viral terminase. J Virol. 2011;85(20):10884\u201393.","journal-title":"J Virol."},{"issue":"8","key":"6694_CR5","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1016\/j.medmal.2018.03.006","volume":"48","author":"P Frange","year":"2018","unstructured":"Frange P, Leruez-Ville M. Maribavir, brincidofovir and letermovir: Efficacy and safety of new antiviral drugs for treating cytomegalovirus infections. Med Mal Infect. 2018;48(8):495\u2013502.","journal-title":"Med Mal Infect."},{"issue":"25","key":"6694_CR6","doi-asserted-by":"publisher","first-page":"2433","DOI":"10.1056\/NEJMoa1706640","volume":"377","author":"FM Marty","year":"2017","unstructured":"Marty FM, Ljungman P, Chemaly RF, Maertens J, Dadwal SS, Duarte RF, Haider S, Ullmann AJ, Katayama Y, Brown J, Mullane KM, Boeckh M, Blumberg EA, Einsele H, Snydman DR, Kanda Y, DiNubile MJ, Teal VL, Wan H, Murata Y, Kartsonis NA, Leavitt RY, Badshah C. Letermovir prophylaxis for cytomegalovirus in hematopoietic-cell transplantation. N Engl J Med. 2017;377(25):2433\u201344.","journal-title":"N Engl J Med."},{"issue":"4","key":"6694_CR7","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1097\/QCO.0000000000000459","volume":"31","author":"RR Razonable","year":"2018","unstructured":"Razonable RR. Role of letermovir for prevention of cytomegalovirus infection after allogeneic haematopoietic stem cell transplantation. Curr Opin Infect Dis. 2018;31(4):286\u201391.","journal-title":"Curr Opin Infect Dis"},{"issue":"10","key":"6694_CR8","doi-asserted-by":"publisher","first-page":"6588","DOI":"10.1128\/AAC.01623-15","volume":"9","author":"S Chou","year":"2015","unstructured":"Chou S. Rapid in vitro evolution of human cytomegalovirus UL56 mutations that confer letermovir resistance. Antimicrob Agents Chemother. 2015;9(10):6588\u201393.","journal-title":"Antimicrob Agents Chemother"},{"issue":"10","key":"6694_CR9","doi-asserted-by":"publisher","first-page":"2775","DOI":"10.1128\/AAC.45.10.2775-2780.2001","volume":"45","author":"NS Lurain","year":"2001","unstructured":"Lurain NS, Weinberg A, Crumpacker CS, Chou S. Sequencing of cytomegalovirus UL97 gene for genotypic antiviral resistance testing. Adult AIDS Clinical Trials Group-CMV Laboratories. Antimicrob Agents Chemother. 2001;45(10):2775\u201380.","journal-title":"Antimicrob Agents Chemother."},{"issue":"3","key":"6694_CR10","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1093\/jac\/dkh065","volume":"53","author":"F Baldanti","year":"2004","unstructured":"Baldanti F, Lilleri D, Campanini G, Comolli G, Ridolfo AL, Rusconi S, Gerna G. Human cytomegalovirus double resistance in a donor-positive\/recipient-negative lung transplant patient with an impaired CD4-mediated specific immune response. J Antimicrob Chemother. 2004;53(3):536\u20139.","journal-title":"J Antimicrob Chemother."},{"issue":"1","key":"6694_CR11","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.jcv.2014.05.017","volume":"61","author":"SA Calarota","year":"2014","unstructured":"Calarota SA, Chiesa A, Scaramuzzi L, Adzasehoun KMG, Comolli G, Mangione F, Esposito P, Baldanti F. Normalizing ELISPOT responses to T-cell counts: a novel approach for quantification of HCMV-specific CD4(+) and CD8(+) T-cell responses in kidney transplant recipients. J Clin Virol. 2014;61(1):65\u201373.","journal-title":"J Clin Virol"},{"key":"6694_CR12","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.antiviral.2014.08.014","volume":"111","author":"L Pilorg\u00e9","year":"2014","unstructured":"Pilorg\u00e9 L, Burrel S, A\u00eft-Arkoub Z, Agut H, Boutolleau D. Human cytomegalovirus (CMV) susceptibility to currently approved antiviral drugs does not impact on CMV terminase complex polymorphism. Antiviral Res. 2014;111:8\u201312. https:\/\/doi.org\/10.1016\/j.antiviral.2014.08.014.","journal-title":"Antiviral Res."},{"issue":"1","key":"6694_CR13","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1128\/AAC.01794-13","volume":"58","author":"T Goldner","year":"2014","unstructured":"Goldner T, Hempel C, Ruebsamen-Schaeff H, Zimmermann H, Lischka P. Geno- and phenotypic characterization of human cytomegalovirus mutants selected in vitro after letermovir (AIC246) exposure. Antimicrob Agents Chemother. 2014;58(1):610\u20133.","journal-title":"Antimicrob Agents Chemother."},{"issue":"6","key":"6694_CR14","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1097\/TP.0000000000002191","volume":"102","author":"CN Kotton","year":"2018","unstructured":"Kotton CN, Kumar D, Caliendo AM, Huprikar S, Chou S, Danziger-Isakov L, Humar A, The Transplantation Society International CMV Consensus Group. The third international consensus guidelines on the management of cytomegalovirus in solid-organ transplantation. Transplantation. 2018;102(6):900\u201331.","journal-title":"Transplantation"},{"issue":"5","key":"6694_CR15","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1016\/j.coph.2008.07.002","volume":"8","author":"P Lischka","year":"2008","unstructured":"Lischka P, Zimmermann H. Antiviral strategies to combat cytomegalovirus infections in transplant recipients. Curr Opin Pharmacol. 2008;8(5):541\u20138.","journal-title":"Curr Opin Pharmacol."},{"issue":"19","key":"6694_CR16","doi-asserted-by":"publisher","first-page":"1781","DOI":"10.1056\/NEJMoa1309533","volume":"370","author":"RF Chemaly","year":"2014","unstructured":"Chemaly RF, Ullmann AJ, Stoelben S, Richard MP, Bornh\u00e4user M, Groth C, Einsele H, Silverman M, Mullane KM, Brown J, Nowak H, K\u00f6lling K, Stobernack HP, Lischka P, Zimmermann H, R\u00fcbsamen-Schaeff H, Champlin RE, Ehninger G. AIC246 Study Team Letermovir for cytomegalovirus prophylaxis in hematopoietic-cell transplantation. N Engl J Med. 2014;370(19):1781\u20139.","journal-title":"N Engl J Med."},{"issue":"1","key":"6694_CR17","doi-asserted-by":"publisher","first-page":"e2019001","DOI":"10.4084\/MJHID.2019.001","volume":"11","author":"JJ Frietsch","year":"2019","unstructured":"Frietsch JJ, Michel D, Stamminger T, Hunstig F, Birndt S, Schnetzke U, Scholl S, Hochhaus A, Hilgendorf I. In vivo emergence of UL56 C325Y cytomegalovirus resistance to letermovir in a patient with acute myeloid leukemia after hematopoietic cell transplantation. Mediterr J Hematol Infect Dis. 2019;11(1):e2019001. https:\/\/doi.org\/10.4084\/MJHID.2019.001.","journal-title":"Mediterr J Hematol Infect Dis."},{"issue":"1","key":"6694_CR18","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1186\/s12879-019-4016-1","volume":"19","author":"S Jung","year":"2019","unstructured":"Jung S, Michel M, Stamminger T, Michel D. Fast breakthrough of resistant cytomegalovirus during secondary letermovir prophylaxis in a hematopoietic stem cell transplant recipient. BMC Infect Dis. 2019;19(1):388. https:\/\/doi.org\/10.1186\/s12879-019-4016-1.","journal-title":"BMC Infect Dis."},{"issue":"6","key":"6694_CR19","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1038\/s41409-018-0389-9","volume":"54","author":"BM Knoll","year":"2019","unstructured":"Knoll BM, Seiter K, Phillips A, Soave R. Breakthrough cytomegalovirus pneumonia in hematopoietic stem cell transplant recipient on letermovir prophylaxis. Bone Marrow Transplant. 2019;54(6):911\u20132.","journal-title":"Bone Marrow Transplant."},{"issue":"12","key":"6694_CR20","doi-asserted-by":"publisher","first-page":"3060","DOI":"10.1111\/ajt.15135","volume":"18","author":"L Cherrier","year":"2018","unstructured":"Cherrier L, Nasar A, Goodlet KJ, Nailor MD, Tokman S, Chou S. Emergence of letermovir resistance in a lung transplant recipient with ganciclovir-resistant cytomegalovirus infection. Am J Transplant. 2018;18(12):3060\u20134.","journal-title":"Am J Transplant."},{"issue":"3","key":"6694_CR21","doi-asserted-by":"publisher","first-page":"e13515","DOI":"10.1111\/tid.13515","volume":"23","author":"E Hofmann","year":"2021","unstructured":"Hofmann E, Sidler D, Dahdal S, Bittel P, Suter-Riniker F, Manuel O, Walti LN, Hirzel C. Emergence of letermovir resistance in solid organ transplant recipients with ganciclovir resistant cytomegalovirus infection: a case series and review of the literature. Transpl Infect Dis. 2021;23(3):e13515.","journal-title":"Transpl Infect Dis"},{"issue":"3","key":"6694_CR22","doi-asserted-by":"publisher","first-page":"e02337","DOI":"10.1128\/AAC.02337-18","volume":"63","author":"N Turner","year":"2019","unstructured":"Turner N, Strand A, Grewal DS, Cox G, Arif S, Baker AW, Maziarz EK, Saullo JH, Wolfe CR. Use of Letermovir as salvage therapy for drug-resistant cytomegalovirus retinitis. Antimicrob Agents Chemother. 2019;63(3):e02337-18. https:\/\/doi.org\/10.1128\/AAC.02337-18.","journal-title":"Antimicrob Agents Chemother"}],"container-title":["BMC Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12879-021-06694-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12879-021-06694-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12879-021-06694-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,23]],"date-time":"2021-09-23T23:06:38Z","timestamp":1632438398000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcinfectdis.biomedcentral.com\/articles\/10.1186\/s12879-021-06694-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,23]]},"references-count":22,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["6694"],"URL":"https:\/\/doi.org\/10.1186\/s12879-021-06694-4","relation":{},"ISSN":["1471-2334"],"issn-type":[{"type":"electronic","value":"1471-2334"}],"subject":[],"published":{"date-parts":[[2021,9,23]]},"assertion":[{"value":"3 December 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 September 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 September 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was performed according to guidelines of the Institutional Review Board of the Fondazione IRCCS Policlinico San Matteo on the use of biologic specimens for scientific purpose in keeping with Italian law (art.13 D. Lgs. 196\/2003).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Patient next-of-kin gave written consent for relative\u2019s clinical details to be published in this study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors report no conflicts of interest in this work.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"994"}}