Drug-resistant cytomegalovirus in transplant recipients: a French cohort study
| Autor: | Sébastien, Hantz, Françoise, Garnier-Geoffroy, Marie-Christine, Mazeron, Isabelle, Garrigue, Pierre, Merville, Catherine, Mengelle, Lionel, Rostaing, Franck, Saint Marcoux, Marie, Essig, Jean-Philippe, Rerolle, Sébastien, Cotin, Raphaëlle, Germi, Sylvie, Pillet, Yvon, Lebranchu, Pascal, Turlure, Sophie, Alain, Patricia, Ribaud |
|---|---|
| Přispěvatelé: | Biologie moléculaire et cellulaire des microorganismes (EA3175), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Bactériologie, Virologie, Hygiène [CHU Limoges], CHU Limoges, Laboratoire de Bactériologie-Virologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service de virologie et d'immunologie biologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Laboratoire de Virologie [Toulouse], CHU Toulouse [Toulouse], Service de Néphrologie - Hypertension Artérielle Dialyse - Transplantation, CHU Toulouse [Toulouse]-Hôpital de Rangueil, Service de Pharmacologie, toxicologie et pharmacovigilance [CHU Limoges], Service de Néphrologie, Dialyse, Transplantations [CHU Limoges], Laboratoire de Virologie, CHU Grenoble, CHU St-Etienne, Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Raherison, Sophie, Service de néphrologie et immunologie clinique, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Adult
Microbiology (medical) Human cytomegalovirus Ganciclovir medicine.medical_specialty Genotype Cytomegalovirus DNA-Directed DNA Polymerase Microbial Sensitivity Tests Drug resistance Antiviral Agents Chemoprevention Cohort Studies Viral Proteins 03 medical and health sciences Internal medicine Drug Resistance Viral medicine Humans Pharmacology (medical) Prospective Studies Child Prospective cohort study 030304 developmental biology Pharmacology 0303 health sciences 030306 microbiology business.industry Hematopoietic Stem Cell Transplantation Valganciclovir Organ Transplantation medicine.disease 3. Good health Multiple drug resistance Transplantation Phosphotransferases (Alcohol Group Acceptor) Phenotype Infectious Diseases Child Preschool Cytomegalovirus Infections Mutation Cohort Immunology France business medicine.drug |
| Zdroj: | Journal of Antimicrobial Chemotherapy Journal of Antimicrobial Chemotherapy, Oxford University Press (OUP), 2010, epub ahead of print. ⟨10.1093/jac/dkq368⟩ Journal of Antimicrobial Chemotherapy, 2010, epub ahead of print. ⟨10.1093/jac/dkq368⟩ |
| ISSN: | 0305-7453 1460-2091 |
| DOI: | 10.1093/jac/dkq368⟩ |
| Popis: | International audience; Objectives Cytomegalovirus (CMV) drug resistance is a therapeutic challenge in the transplant setting. No longitudinal cohort studies of CMV resistance in a real-life setting have been published in the valganciclovir era. We report findings for a French multicentre prospective cohort of 346 patients enrolled at initial diagnosis of CMV infection (clinical trial registered at clinicaltrials.gov: NCT01008540). Patients and methods Patients were monitored for detection of CMV infection for ≥2 years. Real-time detection of resistance by UL97 and UL54 gene sequencing and antiviral phenotyping was performed if viral replication persisted for >21 days of appropriate antiviral treatment. Plasma ganciclovir assays were performed when resistance was suspected. Results Resistance was suspected in 37 (10.7%) patients; 18/37 (5.2% of the cohort) had virological resistance, associated with poorer outcome. Most cases involved single UL97 mutations, but four cases of multidrug resistance were due to UL54 mutations. In solid organ transplant recipients, resistance occurred mainly during primary CMV infection (odds ratio 8.78), but also in two CMV-seropositive kidney recipients. Neither CMV prophylaxis nor antilymphocyte antibody administration was associated with virological resistance. Conclusions These data show the feasibility of surveying resistance. Virological resistance was frequent in patients failing antiviral therapy. More than 1/5 resistant isolates harboured UL54 mutations alone or combined with UL97 mutations, which conferred a high level of resistance and sometimes were responsible for cross-resistance, leading to therapeutic failure. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|