Use of Cidofovir for Cytomegalovirus Disease Refractory to Ganciclovir in Solid Organ Recipients.

Abstract

Solid organ transplantation (SOT) frequently is complicated by cytomegalovirus (CMV) infections. Cidofovir (CDV) is active against CMV, including many ganciclovir (GCV)-resistant mutants, but often is considered to be too nephrotoxic for use after organ transplantation. Seven males and two females (median age 50.1 years), including two kidney/pancreas, four lung, one small bowel, and two hand recipients, received CDV for refractory CMV disease. Three recipients were CMV seronegative, but all nine received grafts from CMV-seropositive donors. Five patients were given antithymocyte globulin, four received daclizumab induction, seven experienced rejection (five with multiple episodes), and one suffered from common variable immunodeficiency. Six presented with other infections (five invasive fungal and four bacterial). Eight patients had received prophylactic GCV, and eight had been treated for CMV infection/disease (GCV eight; CMV immunoglobulin three; foscarnet three). The indications for CDV were UL97 CMV mutation (n = 2), GCV-induced neutropenia with continued CMV disease (n = 4), and clinical resistance to GCV (n = 3). Seven patients cleared CMV, and two had a partial response. Four experienced CMV relapse requiring GCV (n = 2), repeat CDV (n = 1), or CMV immunoglobulin (n = 1). Four patients had mild nephrotoxicity, and three developed renal failure, all in association with additional factors. No patient died directly from CMV disease alone. Two patients died of uncontrolled infections and concurrent CMV disease, one with invasive aspergillosis and another with nocardiosis. Cidofovir was useful for the treatment of GCV-refractory CMV disease after SOT. Although nephrotoxicity was a common complication of CDV, several patients completed a course of therapy successfully and demonstrated effective treatment of CMV disease.