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Clinicians Warned of Drug Resistant H1N1 that Could Happen Fast

Kathleen Blanchard's picture

Researchers from the National Institute of Allergy and Infectious Diseases (NIAID) warn clinicians that drug resistance to H1N1 flu can happen fast. In two cases, and in patients with immune function limitations, drug resistant H1N1 flu developed in less than two weeks.

The study authors say doctors should be aware that even a short course of antiviral therapy with Tamiflu (oseltamivir) or other antiviral drug could lead to drug resistant H1N1 flu quickly.

"While the emergence of drug-resistant influenza virus is not in itself surprising, these cases demonstrate that resistant strains can emerge after only a brief period of drug therapy," says NIAID Director Anthony S. Fauci, M.D. "We have a limited number of drugs available for treating influenza and these findings provide additional urgency to efforts to develop antivirals that attack influenza virus in novel ways."

The patients who developed resistant 2009 H1N1 flu both had blood stem cell transplants several years before contracting the virus. Both patients recovered. In one patient drug resistance developed after 14 days of antiviral therapy and the other in nine days.

Senior author Matthew J. Memoli, M.D. explains, "Although the recommended length of treatment with oseltamivir is five days, it is common for physicians to continue giving this first-line drug longer if the patient does not improve," says Dr. Memoli, as was the case with each patient who developed H1N1 drug resistance.

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Drugs used to treat H1N1 fu include oseltamivir (Tamiflu), peramivir which is a potent intravenous medication that is approved by the FDA for emergency use and still undergoing research, and zanamivir (Relenza).

Tamiflu was given to both patients with H1N1 flu drug resistance for extended period. One patient continued to be ill and showed signs of viral shedding from the nasal mucosa despite treatment. After 24 days of treatment with Tamiflu, physicians administered peramivir for 10 days, then zanamivir for 10 days.

Drug resistant strains of H1N1 had previously been reported in patients after more than 24 days of continuous therapy, and in patients with immune function limitations. In both reported cases, H1N1 resistance developed much faster. Drug resistance associated with H1N1 flu has previously been found from the H275Y genetic mutation of the virus.

Dr. Memoli says it is important for clinicians to choose H1N1 flu treatment options wisely, given the potential for rapid development of drug resistant H1N1 "This is especially important in a patient with prolonged infection or when an antiviral drug fails to cure the patient after the recommended course of treatment."

H1N1 and seasonal flu are both still active in the Southeast States according to a recent report from the CDC, and they continue to encourage vaccination, especially for those at high risk.

Eighty percent of H1N1 flu deaths in 2009 occurred among individuals with an underlying health condition, and most were between the ages of 50 and 64 years. The newest report shows that H1N1 flu drug resistance can happen fast. Clinicians should be aware of the potential for drug resistant H1N1 flu when treating patients with antiviral therapy and who are not improving.

Clinical Infectious Disease: DOI: 10.1086/651605 (2010)