Probable reactivation from latency of multidrug-resistant cytomegalovirus in a lung transplant recipient: A case report.

Whether ganciclovir-resistant cytomegalovirus (ganR-CMV) can establish latency and reactivate absent any selective drug pressure is unknown and has implications for selecting empiric antiviral therapy in patients with prior ganR-CMV. A CMV-seronegative patient underwent bilateral lung transplant from a CMV-seropositive donor and developed biopsy-confirmed CMV colitis with ganR-CMV (UL97 genotype: M460I, A594E; UL54 genotype: F412L, E756D) 4 years posttransplant despite prolonged valganciclovir prophylaxis. Foscarnet therapy led to CMV DNAemia clearance and disease resolution. Plasma CMV DNAemia by sensitive quantitative polymerase chain reaction was not detected in >100 samples over the next 16 years, when she underwent a kidney transplant from a CMV-seronegative donor. Valganciclovir was given for 3 days posttransplant, then switched to letermovir prophylaxis for 3 months. Two months later, CMV syndrome was diagnosed based on compatible symptoms, CMV DNAemia (2.7 × 103 [3.4 log] IU/mL), and the absence of an alternate etiology. Plasma genotype identified M460I and F412L mutations identical to those detected 16 years earlier. These unusual circumstances suggest the establishment of latency with an antiviral-resistant CMV strain and subsequent late reactivation during augmented immunosuppression at the time of a new kidney transplant. Genotypic antiviral resistance testing should be considered even in cases of remote, resolved ganR-CMV infection to guide appropriate antiviral therapy.