Adamantane Resistance Among Influenza A Viruses Isolated Early During the
2005-2006 Influenza Season in the United States 
Conclusions  The high proportion of influenza A viruses currently
circulating demonstrating adamantane resistance indicate that these drugs
should not be used for the treatment or prophylaxis of influenza.
 
Rick A. Bright, PhD; David K. Shay, MD, MPH; Bo Shu, MD; Nancy J. Cox, PhD;
Alexander I. Klimov, PhD 
JAMA. 2006;295:(doi:10.1001/jama.295.8.joc60020). 

Context  The adamantanes, amantadine and rimantadine, have been used as
first-choice antiviral drugs against community outbreaks of influenza A
viruses for many years. Rates of viruses resistant to these drugs have been
increasing globally. Rapid surveillance for the emergence and spread of
resistant viruses has become critical for appropriate treatment of patients.



Objective  To investigate the frequency of adamantane-resistant influenza A
viruses circulating in the United States during the initial months of the
2005-2006 influenza season. 


Design and Setting  Influenza isolates collected from 26 states from October
1 through December 31, 2005, and submitted to the US Centers for Disease
Control and Prevention were tested for drug resistance as part of ongoing
surveillance. Isolates were submitted from World Health Organization
collaborating laboratories and National Respiratory and Enteric Virus
Surveillance System laboratories. 


Main Outcome Measures  Using pyrosequencing and confirmatory assays, we
identified viruses containing mutations within the M2 gene that are known to
confer resistance to both amantadine and rimantadine. 


Results  A total of 209 influenza A(H3N2) viruses isolated from patients in
26 states were screened, of which 193 (92.3%) contained a change at amino
acid 31 (serine to asparagine [S31N]) in the M2 gene known to be correlated
with adamantane resistance. Two of 8 influenza A(H1N1) viruses contained the
same mutation. Drug-resistant viruses were distributed across the United
States. 


Conclusions  The high proportion of influenza A viruses currently
circulating in the United States demonstrating adamantane resistance
highlights the clinical importance of rapid surveillance for antiviral
resistance. Our results indicate that these drugs should not be used for the
treatment or prophylaxis of influenza in the United States until
susceptibility to adamantanes has been reestablished among circulating
influenza A isolates. 


 
Edward E. Rylander,M.D.
Diplomat of the American Board of Family Practice
Diplomat of the American Board of Palliative Medicine