title: Successful ganciclovir treatment of primary cytomegalovirus infection containing the UL97 mutation N510S in an intestinal graft recipient.
abstract: In solid organ transplantation, human cytomegalovirus (HCMV) is considered to be the most important viral pathogen. We report a case of a CMV R-/D+ small intestine transplant recipient with a primary CMV infection on valganciclovir prophylaxis. Sequencing of the HCMV DNA for drug resistance-associated mutations revealed the UL97 mutation N510S. This mutation has been initially reported to confer ganciclovir resistance. Based on in vitro recombinant phenotyping, this assumption has recently been questioned. Switching the antiviral treatment to an intravenous regimen of ganciclovir eliminated HCMV DNAemia, showing the in vivo efficacy of ganciclovir for the UL97 mutation N510S. Hence, knowledge of drug efficacy is crucial for an adequate choice of antiviral medication, carefully balancing antiviral potency versus the risk of harmful side effects.
authors.affiliation: Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, Hoppe-Seyler-Str. 3, Tübingen, Germany. robert.bachmann@med.uni-tuebingen.de
authors.forename: R
authors.initials: R
authors.lastname: Bachmann
authors.forename: K
authors.initials: K
authors.lastname: Hamprecht
authors.forename: J
authors.initials: J
authors.lastname: Lange
authors.forename: R
authors.initials: R
authors.lastname: Ladurner
authors.forename: S
authors.initials: S
authors.lastname: Nadalin
authors.forename: G
authors.initials: G
authors.lastname: Jahn
authors.forename: A
authors.initials: A
authors.lastname: Königsrainer
authors.forename: A
authors.initials: A
authors.lastname: Heininger
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018890:Chemoprevention / Q000379:methods; D003587:Cytomegalovirus / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000175:diagnosis / Q000188:drug therapy*; D004279:DNA, Viral / Q000235:genetics; D024882:Drug Resistance, Viral; D015774:Ganciclovir / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D016867:Immunocompromised Host; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009894:Opportunistic Infections / Q000175:diagnosis / Q000188:drug therapy; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D017422:Sequence Analysis, DNA; D014180:Transplantation; D016896:Treatment Outcome; D000077562:Valganciclovir
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D017853:Phosphotransferases (Alcohol Group Acceptor); C075365:ganciclovir kinase; D000077562:Valganciclovir; D015774:Ganciclovir
references.citation: J Infect Dis. 2002 Sep 15;186(6):760-8
references.pmid: 12198609
references.citation: Lancet. 2000 Aug 19;356(9230):645-9
references.pmid: 10968438
references.citation: Blood. 2003 May 15;101(10):4195-200
references.pmid: 12531791
references.citation: Nat Rev Immunol. 2012 May 25;12(6):459-71
references.pmid: 22627862
references.citation: Nat Rev Nephrol. 2010 Dec;6(12):711-21
references.pmid: 20978468
references.citation: Transplantation. 2011 Dec 15;92(11):1181-7
references.pmid: 22002346
references.citation: Rev Infect Dis. 1990 Sep-Oct;12 Suppl 7:S754-66
references.pmid: 2173105
references.citation: Clin Infect Dis. 2007 Aug 15;45(4):439-47
references.pmid: 17638191
references.citation: Transplantation. 2010 Apr 15;89(7):779-95
references.pmid: 20224515
references.citation: Antimicrob Agents Chemother. 2010 Jun;54(6):2371-8
references.pmid: 20385869
references.citation: Antimicrob Agents Chemother. 2000 Jan;44(1):183-5
references.pmid: 10602745
references.citation: J Infect Dis. 1995 Mar;171(3):576-83
references.pmid: 7876604
references.citation: Clin Microbiol Rev. 2010 Oct;23(4):689-712
references.pmid: 20930070
references.citation: Antimicrob Agents Chemother. 2001 Oct;45(10):2775-80
references.pmid: 11557468
references.citation: J Virol. 1994 Jul;68(7):4427-31
references.pmid: 8207815
references.citation: J Clin Microbiol. 2007 Aug;45(8):2681-3
references.pmid: 17537934
references.citation: J Infect Dis. 1995 Jul;172(1):239-42
references.pmid: 7797920
references.citation: Antimicrob Agents Chemother. 2005 Jul;49(7):2710-5
references.pmid: 15980340
references.citation: Nature. 1992 Jul 9;358(6382):160-2
references.pmid: 1319559