title: Primarily oseltamivir-resistant influenza A (H1N1pdm09) virus evolving into a multidrug-resistant virus carrying H275Y and I223R neuraminidase substitutions.
abstract: Antiviral susceptibility testing and reporting of viruses carrying amino acid substitutions conferring antiviral drug resistance is essential to assess the spread and clinical impact of these viruses. Here, we report on a patient who was infected with a primarily oseltamivir-resistant influenza A (H1N1pdm09) virus following allogeneic stem cell transplantation and rituximab treatment. Under prolonged virus replication and zanamivir therapy the neuraminidase amino acid substitutions H275Y and I223R were detected conferring high-level resistance to oseltamivir and cross-resistance to zanamivir. The emergence of these amino acid changes has been reported rarely worldwide and has been associated with fatal clinical outcomes. The patient survived the influenza infection after 170 days of follow-up.
authors.affiliation: Institute for Virology, Medical Faculty, University of Düsseldorf, Düsseldorf, Germany. sebastian.grund@med.uni-duesseldorf.de.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Grund
authors.forename: Charikleia
authors.initials: C
authors.lastname: Gkioule
authors.forename: Tahani
authors.initials: T
authors.lastname: Termos
authors.forename: Nico
authors.initials: N
authors.lastname: Pfeifer
authors.forename: Guido
authors.initials: G
authors.lastname: Kobbe
authors.forename: Jens
authors.initials: J
authors.lastname: Verheyen
authors.forename: Ortwin
authors.initials: O
authors.lastname: Adams
mesh_terms: D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000627:therapeutic use; D024921:Drug Resistance, Multiple, Viral / Q000187:drug effects / Q000235:genetics*; D019143:Evolution, Molecular; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000235:genetics*; D007251:Influenza, Human / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000150:complications / Q000276:immunology / Q000473:pathology; D009439:Neuraminidase / Q000235:genetics*; D053139:Oseltamivir / Q000627:therapeutic use; D014764:Viral Proteins / Q000235:genetics*; D053243:Zanamivir / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D014764:Viral Proteins; D053139:Oseltamivir; D009439:Neuraminidase; D053243:Zanamivir