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.