Emergence of ganciclovir-resistant cytomegalovirus in lung transplant recipients

J Heart Lung Transplant. 2002 Dec;21(12):1274-82. doi: 10.1016/s1053-2498(02)00463-1.


Background: Since ganciclovir-resistant cytomegalovirus (CMV) disease was initially described in a patient with acquired immunodeficiency syndrome (AIDS) in 1986, the incidence of ganciclovir-resistant CMV disease appears to be increasing in immunocompromised patients. More recently, there have been sporadic reports of ganciclovir-resistant CMV disease in solid organ transplantation.

Methods: We retrospectively assessed the incidence of ganciclovir-resistant CMV disease in all lung transplant recipients transplanted between 6/93 and 6/01 at Loyola University Medical Center. All patients underwent routine CMV blood culture, shell vial assay as well as phenotypic and genotypic anti-viral susceptibility testing according to a pre-determined schedule. The number of CMV episodes, intravenous ganciclovir use, acute and chronic rejection and survival data were documented for all patients.

Results: Twelve of 212 (6%) transplant recipients developed ganciclovir-resistant CMV disease. Ganciclovir resistance was associated with a higher number of CMV episodes (3.4 +/- 2.3 episodes/patient vs 1.7 +/- 0.7 episodes/patient [p < 0.05]) and an increased exposure to cumulative intravenous ganciclovir in the primary CMV-mismatched (D(+)R(-)) population (22 +/- 10 vs 13 +/- 7 days [p < 0.05]) compared with patients who did not develop ganciclovir resistance. In addition, the use of daclizumab therapy was associated with a 7-fold greater likelihood of developing ganciclovir resistance (p < 0.0001). The presence of ganciclovir-resistant CMV disease in our population was associated with a decreased survival that could be attributed to CMV disease itself (p < 0.05).

Conclusions: By screening all lung transplant recipients with CMV disease for ganciclovir resistance, we were able to detect a higher incidence of ganciclovir-resistant CMV disease (6%) than previously seen in solid organ transplantation. High-risk patients (D(+)R(-) CMV serostatus) who receive anti-lymphocytic therapy should be monitored aggressively and treated to prevent the development of ganciclovir resistance and avert a negative outcome.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Case-Control Studies
  • Cytomegalovirus / drug effects*
  • Cytomegalovirus / isolation & purification
  • Cytomegalovirus Infections / diagnosis*
  • Cytomegalovirus Infections / drug therapy
  • Cytomegalovirus Infections / epidemiology*
  • DNA, Viral / analysis
  • Drug Resistance, Microbial
  • Female
  • Follow-Up Studies
  • Ganciclovir / therapeutic use*
  • Graft Rejection
  • Graft Survival
  • Humans
  • Lung Transplantation / adverse effects*
  • Lung Transplantation / immunology
  • Lung Transplantation / mortality
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Opportunistic Infections / diagnosis*
  • Opportunistic Infections / epidemiology
  • Polymerase Chain Reaction
  • Postoperative Complications / epidemiology
  • Postoperative Complications / virology*
  • Probability
  • Reference Values
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Statistics, Nonparametric
  • Survival Rate
  • Transplantation Immunology / physiology


  • DNA, Viral
  • Ganciclovir