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

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

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Department of Pediatrics, Microbiology, Medicine and Neurosurgery, University of Alabama at Birmingham, 303 CHB, 1600 Seventh Ave S, Birmingham, AL 35233, USA.

Erratum in

  • Clin Infect Dis. 2014 Apr;58(8):1203.



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.


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.


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.


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.

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