A 34-year-old man admitted to ICU with severe influenza A(H1N1)pdm09 pneumonia is started on oral oseltamivir but deteriorates. Neuraminidase gene sequencing of his isolate shows the H275Y substitution. The most appropriate management change is:

• A Continue oseltamivir at the same dose, since H275Y does not affect susceptibility
• B Discontinue all antivirals, since resistance means no drug will help
• C Add amantadine, since adamantanes retain activity against H275Y mutants
• D Switch therapy to a neuraminidase inhibitor unaffected by H275Y, such as zanamivir ✓

Explanation

The H275Y substitution in the neuraminidase of influenza A(H1N1)pdm09 markedly reduces susceptibility to oseltamivir while sparing zanamivir, so switching or adding zanamivir is the accepted response in severe disease. Amantadine acts on the M2 ion channel and circulating H1N1pdm09 strains are essentially universally resistant to adamantanes, making option C incorrect. Stopping antivirals entirely is inappropriate in severe illness.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.