title: Recurrent and persistent cytomegalovirus infection in a kidney recipient caused by the L595S mutation in UL97 phosphotransferase gene.
abstract: Ganciclovir (GCV) is the first therapeutic choice for prevention and treatment of active cytomegalovirus (CMV) infection in solid organ transplant recipients in Bahia state, Brazil. Prolonged and repeated GCV therapy may result in drug-resistant virus, associated with progressive and disseminated disease. We present a case report of a young male kidney recipient, who was CMV-seronegative with a CMV-seropositive donor (D(+)/R(-)), and who developed clinical GCV resistance, confirmed by mutation in viral UL97 phosphotransferase responsible for GCV activation. Under prophylactic therapy with intravenous GCV for 6 weeks post-transplantation, he developed severe anaemia and hepatic enzyme increases, probably due to drug side effects. At this moment, the drug was discontinued and he started to be monitored by pp65 antigen test. At week 10 post-transplantation, he presented fever, myalgia, thrombocytopenia and neutropaenia, with a positive CMV antigen test. During treatment with intravenous GCV, antigenaemia assay demonstrated a higher number of positive cells, requiring GCV at higher doses. Pre-emptive therapy lasted for 31 days and he started the maintenance therapy with oral GCV. However, antigenaemia assay demonstrated an extremely high number of positive cells, and he was rehospitalized and prescribed intravenous GCV. Severe leukopaenia led to GCV interruption, but immunosuppressive dose reduction helped to control the active CMV infection. GCV-resistant CMV infection resulted in increased morbidity, rehospitalization episodes and increased costs; therefore, implementation of resistance diagnostic tests in the transplantation routine is of great importance. We documented the first case of GCV-resistant CMV infection due to the L595S mutation in UL97 phosphotransferase gene in a kidney recipient from Bahia state, Brazil.
authors.affiliation: Laboratório Avançado de Saúde Pública, Oswaldo Cruz Fundation, Salvador, Brazil.
authors.forename: Maíra
authors.initials: M
authors.lastname: Peixoto
authors.forename: Lays
authors.initials: L
authors.lastname: Mascarenhas
authors.forename: André
authors.initials: A
authors.lastname: Cunha
authors.forename: Margarida
authors.initials: M
authors.lastname: Dutra
authors.forename: Eva
authors.initials: E
authors.lastname: Miranda
authors.forename: Ivo
authors.initials: I
authors.lastname: Silva
authors.forename: Sandra
authors.initials: S
authors.lastname: Costa
authors.forename: Bernardo
authors.initials: B
authors.lastname: Galvão
authors.forename: Andréa
authors.initials: A
authors.lastname: Cunha
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001938:Brazil; D003587:Cytomegalovirus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000821:virology; D024882:Drug Resistance, Viral / Q000235:genetics*; D015774:Ganciclovir / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D009154:Mutation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D012008:Recurrence; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D017853:Phosphotransferases (Alcohol Group Acceptor); C075365:ganciclovir kinase; D015774:Ganciclovir