The impact of ganciclovir-resistant cytomegalovirus infection after lung transplantation

Background. Cytomegalovirus (CMV) resistance to ganciclovir has become incr easingly common in acquired immunodeficiency syndrome patients but has only rarely been reported in recipients of solid organ transplants. Methods. A retrospective study of ganciclovir susceptibility testing of CMV isolates recovered from lung transplant recipients was performed. Patients with CMV isolates having partial (1<IC50<3 mu g/ml) or full resistance (IC 50 greater than or equal to 3 mu g/ml) to ganciclovir determined by plaque reduction assay were included in a case-control study to identify risk fact ors for ganciclovir resistance. Results. Between 2/91 and 5/98, 18 patients (5.2% of patients transplanted) were found to have CMV infections with some degree of ganciclovir resistan ce (4 partially, 14 fully resistant). More positive viral blood cultures (3 .2+/-2.5 vs. 1.6+/-1.4 CMV positive cultures, P=0.02) and more episodes of CMV pneumonitis (0.24+/-0.23 vs. 0.10+/-0.17 episodes/bronchoscopy, P=0.02) occurring before the detection of resistance were seen among resistant pat ients than controls. Ganciclovir-resistant patients received more antithymo cyte globulin during induction (70+/-44 vs. 45+/-39 mg/kg, P=0.03) and rece ived ganciclovir for a greater number of days (79+/-52 vs. 64+/-53 days, P= 0.005) before the detection of resistance than controls. Ganciclovir-resist ant patients had a shorter survival and an earlier onset of bronchiolitis o bliterans syndrome compared with patients in the transplant database at Was hington University. Conclusions. Ganciclovir-resistant CMV infection is a serious complication of solid organ transplantation associated with more episodes of viremia, mo re frequent disease, earlier onset of bronchiolitis obliterans and shorter survival. The use of antithymocyte globulin and prolonged exposure to ganci clovir are risk factors for the development of ganciclovir resistance.