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Emergence of ganciclovir-resistant cytomegalovirus in lung transplant recipients
Authors:Sangeeta M. Bhorade MD   Nell S. Lurain PhD   Ashby Jordan MD   Julie Leischner MD   Jaime Villanueva MD   Ramon Durazo PhD   Steve Creech MS   Wickii T. Vigneswaran MD  Edward R. Garrity MD
Affiliation:Lung Transplant Program, Division of Pulmonary Medicine, Loyola University Medical Center, 2160 South First Avenue, Maywood, IL 60153, USA.
Abstract: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.
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