Global assessment of resistance to neuraminidase inhibitors, 2008-2011: the Influenza Resistance Information Study (IRIS)

Clin Infect Dis. 2013 May;56(9):1197-205. doi: 10.1093/cid/cis1220. Epub 2013 Jan 10.

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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Antiviral Agents / pharmacology*
  • Antiviral Agents / therapeutic use
  • Child
  • Child, Preschool
  • Drug Resistance, Viral*
  • Female
  • Humans
  • Infant
  • Influenza A virus / drug effects*
  • Influenza, Human / virology*
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Neuraminidase / antagonists & inhibitors*
  • Oseltamivir / pharmacology*
  • Oseltamivir / therapeutic use
  • Prospective Studies
  • RNA, Viral / genetics
  • Treatment Outcome
  • Viral Load
  • Young Adult

Substances

  • Antiviral Agents
  • RNA, Viral
  • Oseltamivir
  • Neuraminidase