title: Rapid selection of a transmissible multidrug-resistant influenza A/H3N2 virus in an immunocompromised host.
abstract: BACKGROUND
  The overall impact of influenza virus infection in immunocompromised patients is largely unknown. Antigenic drift and genetic variations during prolonged influenza infection have been demonstrated. In this report we describe a multidrug-resistant H3N2 influenza virus isolated from an immunocompromised patient after 5 days of therapy.
  
  
  METHODS
  Multiple nasal wash samples were collected from an infected patient, and viral isolates were characterized. Sensitivity to antiviral agents was evaluated. Fitness and transmissibility were assessed in ferrets and tissue culture.
  
  
  RESULTS
  An in-frame 4-amino acid deletion emerged in the neuraminidase (NA) gene of an H3N2 virus after 5 days of oseltamivir therapy. No other changes in the NA or hemagglutinin genes were noted. Drug sensitivity assays revealed resistance to oseltamivir (>10-fold increase in 50% inhibitory concentration [IC(50)]) and reduction in sensitivity to zanamivir (3-7-fold increase in IC(50) or 50% effective concentration). No change in fitness or transmissibility was observed.
  
  
  CONCLUSIONS
  An in-frame NA gene deletion was rapidly selected for in an immunocompromised patient, resulting in decreased sensitivity of the isolate to available NA inhibitors without a change in fitness or transmissibility. This finding has implications for our understanding of the emergence of antiviral resistance and treatment of patients with influenza A infection, especially those who are immunocompromised.
authors.affiliation: Respiratory Virus Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, MSC 3203 33 North Dr, Bethesda, MD 20892-3203, USA. memolim@niaid.nih.gov
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Memoli
authors.forename: Rachel J
authors.initials: RJ
authors.lastname: Hrabal
authors.forename: Arash
authors.initials: A
authors.lastname: Hassantoufighi
authors.forename: Brett W
authors.initials: BW
authors.lastname: Jagger
authors.forename: Zong-Mei
authors.initials: ZM
authors.lastname: Sheng
authors.forename: Maryna C
authors.initials: MC
authors.lastname: Eichelberger
authors.forename: Jeffery K
authors.initials: JK
authors.lastname: Taubenberger
mesh_terms: D000328:Adult; D000818:Animals; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics; D005289:Ferrets / Q000821:virology; D006801:Humans; D016867:Immunocompromised Host; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects* / Q000235:genetics; D007251:Influenza, Human / Q000188:drug therapy / Q000276:immunology / Q000635:transmission / Q000821:virology*; D020522:Lymphoma, Mantle-Cell / Q000150:complications / Q000821:virology; D008297:Male; D008969:Molecular Sequence Data; D009976:Orthomyxoviridae Infections / Q000635:transmission / Q000821:virology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014779:Virus Replication / Q000235:genetics