Clin Infect Dis. 2013 Jan 10. [Epub ahead of print]
Global Assessment of Resistance to Neuraminidase Inhibitors: 2008-2011. The Influenza Resistance Information Study (IRIS).
Source
Department of Pediatrics, Microbiology, Medicine and Neurosurgery, University of Alabama at Birmingham, Birmingham, AL, USA.
Abstract
Background. Following emergence of naturally occurring oseltamivir-resistant 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 real-time 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 post-baseline (17 H1N1pdm2009 [H275Y]; 2 H3N2 [R292 K]), 14 of whom were children aged ≤5 years. In 12/19 patients, viral loads were too low to permit cell culture and 14/19 were RT-qPCR-negative by Day 10. In one other H1N1pdm2009 patient, H275Y was detected by sequencing but not 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 1-5 year-olds. Viral loads were low in many cases and viral clearance rapid.
Methods. Patients with influenza-like illness and/or positive rapid test results agreed to swabs of the posterior nares that were assessed by real-time 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 post-baseline (17 H1N1pdm2009 [H275Y]; 2 H3N2 [R292 K]), 14 of whom were children aged ≤5 years. In 12/19 patients, viral loads were too low to permit cell culture and 14/19 were RT-qPCR-negative by Day 10. In one other H1N1pdm2009 patient, H275Y was detected by sequencing but not 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 1-5 year-olds. Viral loads were low in many cases and viral clearance rapid.
No comments:
Post a Comment