[Ganciclovir-resistant cytomegalovirus infection: 2 cases with different clinical impact]

Swiss cases of cytomegalovirus (CMV) resistance to antiviral drugs have not been reported to date. We describe both a documented and a presumed case of ganciclovir-resistant CMV infection. A bone marrow transplant recipient with an episode of CMV viremia and antigenemia underwent broncho-alveolar lavage from which a CMV strain was isolated. The sensitivity of this strain to ganciclovir and foscarnet was tested in a plaque reduction assay, which was performed in 6 different fibroblast lines. The inhibitory drug concentration which reduced viral plaque formation by 50% (IC50) was a median of 12.7 microM (range 6.1-29.6) for ganciclovir (resistance defined as IC50 > 6 microM), which documented the presence of CMV resistance to ganciclovir. The strain was sensitive to foscarnet. This ganciclovir-resistant CMV strain had no clinical impact, although the patient was treated with ganciclovir. A second patient had Aids and subsequently developed CMV retinitis which was treated with intravenous ganciclovir for 3 weeks, followed by longterm oral ganciclovir therapy. Approximately 4 1/2 months after initiation of antiviral therapy the patient developed fatal CMV multi-organ disease while on continued oral ganciclovir treatment, which suggested the occurrence of CMV resistance to this agent. CMV organ disease was documented at autopsy by histology and immunochemistry, but virus was not cultured. The different outcomes in these two patients suggest that the type of underlying immunodeficiency may be a decisive factor for the clinical relevance of drug-resistant CMV infection.