title: Failure of pre-emptive treatment of cytomegalovirus infections and antiviral resistance in stem cell transplant recipients.
abstract: BACKGROUND
  Treatment of cytomegalovirus (CMV) infections after stem cell transplantation (SCT) does not always lead to a rapid viral response. The causes of treatment failure may be either viral resistance or immunological failure to control viral replication. This study investigated the response to pre-emptive treatment in CMV infections in order to define risk factors for treatment failure, including the role of antiviral resistance.
  
  
  METHODS
  Adult recipients of allogeneic T-cell depleted SCT were studied retrospectively (n=92). CMV infections were treated with (val)ganciclovir according to a CMV DNA-load-based pre-emptive strategy. Treatment failure was defined as a CMV DNA load of 1,000 copies/ml or more after at least 2 weeks of treatment. Resistance was analysed by nucleotide sequence analysis of the UL97 and UL54 genes in the first CMV DNA-positive sample and in samples during treatment failure.
  
  
  RESULTS
  Treatment failure occurred in 26 of the 47 pre-emptively treated patients (55%) and in 39 of 86 (45%) treatment episodes. The risk of treatment failure was increased during first treatment episodes (P=0.01) and during the use of immunosuppressive medication (P=0.02). Antiviral resistance was found in only 1 patient (4%) with treatment failure.
  
  
  CONCLUSIONS
  A slow response to pre-emptive antiviral treatment occurred frequently in CMV infections in SCT recipients. Antiviral resistance was observed but played a minor role in treatment failure.
authors.affiliation: Department of Medical Microbiology, Leiden University Medical Center, Leiden, the Netherlands. m.t.van_der_beek@lumc.nl.
authors.forename: Martha T
authors.initials: MT
authors.lastname: van der Beek
authors.forename: Erik W A F
authors.initials: EW
authors.lastname: Marijt
authors.forename: Ann C T M
authors.initials: AC
authors.lastname: Vossen
authors.forename: Caroline S
authors.initials: CS
authors.lastname: van der Blij-de Brouwer
authors.forename: Ron
authors.initials: R
authors.lastname: Wolterbeek
authors.forename: Constantijn J M
authors.initials: CJ
authors.lastname: Halkes
authors.forename: Eric C J
authors.initials: EC
authors.lastname: Claas
authors.forename: Aloys C M
authors.initials: AC
authors.lastname: Kroes
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D003586:Cytomegalovirus Infections / Q000188:drug therapy* / Q000821:virology; D004279:DNA, Viral / Q000032:analysis; D024882:Drug Resistance, Viral; D005260:Female; D015774:Ganciclovir / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D055502:Secondary Prevention; D017422:Sequence Analysis, DNA; D033581:Stem Cell Transplantation; D014184:Transplantation, Homologous; D017211:Treatment Failure; D019562:Viral Load / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D007166:Immunosuppressive Agents; D015774:Ganciclovir