Ganciclovir-resistant cytomegalovirus (CMV) is associated with significant morbidity in solid organ transplant recipients. Management of ganciclovir-resistant CMV may be complicated by nephrotoxicity which is commonly observed with recommended therapies and/or rejection induced by “indirect” viral effects or reduction of immunosuppression. Herein, we report a series of four high serologic risk (donor CMV positive/recipient CMV negative) kidney transplant patients diagnosed with ganciclovir-resistant CMV disease. All patients initially developed “breakthrough” viremia while still receiving valganciclovir prophylaxis after transplant and were later confirmed to exhibit UL97 mutations after failing to eradicate virus on adequate dosages of valganciclovir. The patients were subsequently and successfully treated with reduced-dose (1-2？mg/kg) cidofovir and CMV-hyperimmune globulin, given in 2-week intervals. In addition, all patients exhibited stable renal function after completion of therapy, and none experienced acute rejection. The combination of reduced-dose cidofovir and CMV-hyperimmune globulin appeared to be a safe and effective regimen in patients with mild disease due to ganciclovir-resistant CMV. 1. Introduction Cytomegalovirus (CMV) is a significant cause of morbidity among solid organ transplant recipients. Active infection can result in the well-defined direct effects of either CMV syndrome or tissue-invasive disease, while the “indirect effects” include potential immune-mediated injury of the allograft as well as an increased propensity for coinfections [1]. Ganciclovir and its prodrug, valganciclovir, each have been effective in both prevention and treatment of CMV disease [2–4]. However, the emergence of ganciclovir-resistant (GCV-R) CMV has posed a more significant threat due to an aggressive disease course and a greater mortality risk [5]. Treatment options for GCV-R CMV are limited, with foscarnet being recommended as the initial treatment option followed by cidofovir [6]. Although these agents are known to have activity against CMV, both are associated with substantial side effects, the most notable of which is nephrotoxicity. Significant renal injury with these agents has been reported in 30–60% of patients and may even occur after only 1-2 doses [7, 8]. Furthermore, cidofovir is contraindicated in patients with an estimated creatinine clearance of 55？mL/min or a serum creatinine of 1.5？mg/dL [8], which are common findings among the solid organ transplant population. Herein, we report a successful strategy of reduced-dose cidofovir in
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