title: Global assessment of resistance to neuraminidase inhibitors, 2008-2011: the Influenza Resistance Information Study (IRIS).
abstract: BACKGROUND
  Following emergence of naturally occurring oseltamivir-resistant influenza A(H1N1) viruses, a global observational investigation, the Influenza Resistance Information Study (IRIS; NCT00884117), was initiated in 2008 to study neuraminidase inhibitor (NAI) resistance and clinical outcome.
  
  
  METHODS
  Patients with influenza-like illness and/or positive rapid test results agreed to swabs of the posterior nares that were assessed by semiquantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) for influenza type and subtype and NAI resistance. RT-qPCR-positive specimens were cultured, sequenced, and phenotypically tested for NAI resistance. Treatment was at the physician's discretion.
  
  
  RESULTS
  Of 1799 influenza-positive (RT-qPCR) patients, 1281 had influenza A (47 seasonal H1N1; 335 H3N2; 899 H1N1pdm2009) and 518 had influenza B. Antivirals were administered to 1041 (58%) patients (26, 245, 514, and 256, respectively). All seasonal H1N1 strains were genotypically (H275Y) and phenotypically resistant to oseltamivir. No genotypic resistance was detected in the day 1 samples of any other viral subtypes. Mutation-specific (MS) RT-PCR detected resistance to oseltamivir in 19 patients postbaseline (17 H1N1pdm2009 [H275Y]; 2 H3N2 [R292K]), 14 of whom were children aged ≤5 years. In 12 of 19 patients, viral loads were too low to permit cell culture and 14 of 19 were RT-qPCR negative by day 10. In 1 other H1N1pdm2009 patient, H275Y was detected by sequencing but not by MS RT-PCR. No emergent resistance was found in influenza B infections.
  
  
  CONCLUSIONS
  In years 1-3 of IRIS, emergent resistance to oseltamivir in influenza viruses during treatment was uncommon (2.2%) and mostly found in patients aged 1-5 years. Viral loads were low in many cases and viral clearance rapid.
authors: Department of Pediatrics, Microbiology, Medicine and Neurosurgery, University of Alabama at Birmingham, 303 CHB, 1600 Seventh Ave S, Birmingham, AL 35233, USA. rwhitley@peds.uab.edu
authors: Richard J
authors: RJ
authors: Whitley
authors: Charles A
authors: CA
authors: Boucher
authors: Bruno
authors: B
authors: Lina
authors: Jonathan S
authors: JS
authors: Nguyen-Van-Tam
authors: Albert
authors: A
authors: Osterhaus
authors: Martin
authors: M
authors: Schutten
authors: Arnold S
authors: AS
authors: Monto
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D024882:Drug Resistance, Viral; D005260:Female; D006801:Humans; D007223:Infant; D009980:Influenza A virus / Q000187:drug effects*; D007251:Influenza, Human / Q000821:virology*; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D053139:Oseltamivir / Q000494:pharmacology* / Q000627:therapeutic use; D011446:Prospective Studies; D012367:RNA, Viral / Q000235:genetics; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D012367:RNA, Viral; D053139:Oseltamivir; D009439:Neuraminidase