title: Emergence of drug-resistant cytomegalovirus in the era of valganciclovir prophylaxis: therapeutic implications and outcomes.
abstract: BACKGROUND
  Valganciclovir prophylaxis is reportedly associated with a low incidence of ganciclovir-resistant cytomegalovirus (CMV). We assessed the incidence, clinical features, and outcome of drug-resistant CMV among solid organ transplant patients who received valganciclovir prophylaxis.
  
  
  METHODS
  The medical records of all CMV D+/R- kidney, pancreas, liver, and heart recipients were screened for CMV disease, and the clinical course and outcomes of patients with drug-resistant CMV were reviewed.
  
  
  RESULTS
  During a four-yr-study period, a total of 225 CMV D+/R- transplant patients received valganciclovir prophylaxis for a median of 92 d. Sixty-five (29%) of the 225 patients developed delayed-onset primary CMV disease, including nine (14%) suspected to have drug-resistant virus. Four (6.2%) had confirmed UL97 or UL54 mutations. All except one patient manifested gastrointestinal tissue-invasive disease. Together with reduction in immunosuppression, intravenous foscarnet with or without CMV hyperimmunoglobulin was the most common treatment. Drug-associated nephrotoxicity was commonly observed and resulted in allograft loss in two patients. During the mean follow-up of 2.2 yr, allograft loss and mortality occurred in two of four patients with proven and in three of five patients with clinically suspected drug-resistant CMV.
  
  
  CONCLUSIONS
  Cytomegalovirus disease because of clinically suspected or genotypically confirmed drug-resistant CMV is not uncommon in CMV D+/R- solid organ transplant patients who received valganciclovir prophylaxis. Because of its significant morbidity and mortality, an optimized strategy of CMV prevention is warranted to reduce the negative impact of drug-resistant CMV on the successful outcome of organ transplantation.
authors.affiliation: Division of Infectious Diseases, The William J. von Liebig Transplant Center, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Eid
authors.forename: Supha K
authors.initials: SK
authors.lastname: Arthurs
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Deziel
authors.forename: Mark P
authors.initials: MP
authors.lastname: Wilhelm
authors.forename: Raymund R
authors.initials: RR
authors.lastname: Razonable
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003587:Cytomegalovirus / Q000187:drug effects*; D003586:Cytomegalovirus Infections / Q000517:prevention & control*; D024882:Drug Resistance, Viral; D005260:Female; D015774:Ganciclovir / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D008910:Minnesota / Q000453:epidemiology; D012189:Retrospective Studies; D014180:Transplantation / Q000009:adverse effects*; D000077562:Valganciclovir
chemical_list: D000998:Antiviral Agents; D000077562:Valganciclovir; D015774:Ganciclovir