Incidence and Outcomes of Ganciclovir-Resistant Cytomegalovirus Infections in 1244 Kidney Transplant Recipients

Background. Cytomegalovirus (CMV) infections in kidney transplant recipients are in most cases successfully treated with oral valganciclovir (VGCV). However, in a few percent of patients, mutations in the UL 97 or UL 54 gene lead to drug resistance. Methods. We investigated the incidence and outcomes of ganciclovir-resistant CMV viremia in all 1244 kidney recipients transplanted at our center from 2004 through 2008. CMV DNAemia was monitored in all patients at least weekly, and patients who were positive were treated preemptively with VGCV (900 mg once daily). Results. Ganciclovir-resistant mutations were detected in 27 patients (2.2%), of which 26 occurred in the 209 CMV IgG-negative recipients receiving a CMV-positive kidney (12.5%). All had UL97 gene mutations, and none had UL54 gene mutations. Mean DNAemia half-life for the first (nonresistance) episode of CMV viremia was 3.8 +/- 1.2 days. After established resistance, 25 of 27 patients had their mycophenolate mofetil dose reduced by approximately 50%, and 10 of these were also treated with intravenous foscarnet. The DNAemia half-life was 3.7 +/- 1.4 days in the foscarnet-treated patients, significantly shorter than in the other 17 patients, 10.8 +/- 6.7 days (P=0.001). Time to DNAemia eradication was 30 +/- 16 and 81 +/- 51 days in the two groups, respectively (P=0.001). Conclusion. Use of 900 mg VGCV once daily for preemptive CMV treatment is associated with a high incidence of CMV UL97-resistance gene mutations in D+/R- patients. Foscarnet treatment rapidly and safely eradicated CMV DNAemia, and also patients who only reduced the immunosuppression and continued on VGCV treatment eventually cleared the virus.