Oseltamivir-resistant novel influenza A (H1N1) virus infection in two immunosuppressed patients - Seattle, Washington, 2009

Abstract

Novel influenza A (H1N1) virus infection continues to cause illness and death among persons worldwide. Immunosuppressed patients with influenza virus infection can shed virus for prolonged periods, increasing the chances for development of drug resistance. On August 6, 2009, CDC detected evidence of resistance to the antiviral medication oseltamivir in two severely immunosuppressed patients with novel influenza A (H1N1) virus infection in Seattle, Washington. The two patients were treated in two different hospitals, and their cases were not epidemiologically linked. Both were being treated with oseltamivir for novel influenza A (H1N1) virus infection and had prolonged viral shedding. In both patients, the virus was documented as initially susceptible to oseltamivir, and resistance developed subsequently during treatment with the drug. Testing of viral RNA from both patients by pyrosequencing detected a mutation that results in a histidine-to-tyrosine substitution at position 275 (H275Y) in the neuraminidase, known to be associated with oseltamivir resistance. The results were confirmed by pyrosequencing, sequencing of the neuraminidase gene, and neuraminidase inhibition testing of virus isolates on August 11. One patient's symptoms resolved after treatment with oseltamivir, and the other patient was receiving treatment with zanamivir and ribavirin as of August 13. An investigation of health-care personnel (HCP) contacts and other close contacts revealed no evidence of virus transmission. This report summarizes the case histories and resulting investigations and highlights the importance of 1) close monitoring for antiviral drug resistance among immunosuppressed patients receiving treatment for novel influenza A (H1N1) virus infection and 2) the implications for infection control.