A 22-year-old woman, whose immune system was impaired due to recent chemotherapy, has survived a serious case of swine-flu after being treated with the unlicensed intravenous form of relenza, in combination with high-dose corticosteroids. The Case Report is published Online First and in an upcoming edition of The Lancet, and is Dr Michael Kidd and Dr Mervyn Singer, University College London Hospitals NHS Foundation Trust, London, UK, and colleagues.

The woman had received chemotherapy as part of treatment for Hodgkin's disease, and on July 8 this year was referred to the Intensive Care Unit (ICU) at University College Hospital. She had laboratory-confirmed H1N1 infection, increasing shortness of breath, build-up of fluid in both lungs-and her condition was not responding either to tamiflu 75mg twice daily or broad-spectrum antimicrobials. Progressive deterioration meant she needed artificial ventilation from day 3 of her ICU admission. Since she did not appear to be absorbing the tamiflu, this was switched to nebulised relenza for ICU days 6-13. However this had no obvious clinical benefit, and high levels of H1N1 RNA were detected on day ICU 10. Increasing the relenza dose for ICU days 13-16 did not improve her clinical state.

As she remained critically ill with severe respiratory failure, doctors decided on day 16 to begin treatment using unlicensed intravenous relenza (provided by GlaxoSmithKline). Agreement for this was granted by the hospital and next-of-kin. Treatment with the corticosteroid methylprednisolone was also started to treat the lung inflammation. The patient's condition improved within 48 hours-H1N1 viral load had decreased over 100-fold by ICU day 21. She was extubated the same day, and discharged back to the ward after 24 days in ICU. Inhaled relenza was continued as a precaution due to her immunocompromised state.

The authors say: "Since her inflamed, atelectatic* lungs were probably impeding adequate drug absorption, and clinical improvement was not forthcoming, we decided to use intravenous (unlicensed) zanamivir. High dosing achieves effective respiratory epithelial concentrations and is well-tolerated. Our patient progressively recovered with no drug related side-effects."

Deaths due to pandemic H1N1 influenza are mainly related to severe respiratory failure, or acute respiratory distress syndrome (ARDS). The authors suggest that persistent high level H1N1 replication may drive ongoing lung inflammation, and that the intravenous relenza and high-dose corticosteroids could have worked together in this case, although this may be considered controversial and high-dose corticosteroids are not recommended in swine influenza treatment guidelines. The authors say: "However, controlled trials are lacking and a rationale does exist for the use of corticosteroids in ARDS."

They conclude: "Although this is a single case report and direct cause and effect cannot be confirmed, the improvement in clinical status following intravenous relenza encourages prompt further investigation, both alone and in combination with high-dose methylprednisolone."

Link to case report

Source
The Lancet

View drug information on Relenza; Tamiflu capsule.

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