during october 1 , 2010july 31 , 2011 , the centers for disease control and prevention ( cdc ; atlanta , georgia , usa ) asked all state public health laboratories to submit pandemic ( h1n1 ) 2009 virus  positive respiratory specimens and virus isolates for antiviral susceptibility testing . laboratories were asked to provide the first 5 specimens of any type / subtype collected during each 2-week period for virus isolation .
comprehensive antiviral testing , including neuraminidase inhibition ( ni ) assay , was performed on all isolates , and sequencing was performed on all isolates with elevated 50% inhibitory concentration values .
cdc also requested that laboratories provide 5 additional specimens every 2 weeks for pyrosequencing to identify the h275y substitution in the neuraminidase , a change associated with oseltamivir resistance ( 3 ) .
in addition to ( or instead of ) participating in the national surveillance , state laboratories in california , maine , maryland , minnesota , new york , texas , and washington performed pyrosequencing on state surveillance specimens to detect the h275y substitution .
we included those state - specific data in the national surveillance data for this report .
state health departments used a standard case form to collect demographic and clinical information for patients with oseltamivir - resistant pandemic ( h1n1 ) 2009 virus infection and their ill close contacts .
oseltamivir resistance was determined by use of an ni assay or pyrosequencing for the h275y substitution . for ni testing on isolates
, we used the na - fluor kit ( applied biosystems , foster city , ca , usa ) as described ( 4 ) .
we performed pyrosequencing , as described ( 5 ) , on all oseltamivir - resistant pandemic ( h1n1 ) 2009 isolates identified by ni assay to confirm the presence of the h275y substitution .
we performed pyrosequencing for h275y , without the ni assay , to screen pandemic ( h1n1 ) 2009 clinical specimens ( 5 ) .
for the national surveillance , ni testing was performed at cdc and pyrosequencing was performed at cdc and at state laboratories in wisconsin , new york , and california .
state laboratories followed pyrosequencing protocols provided by cdc ; when possible , cdc confirmed results for resistant viruses by use of pyrosequencing and ni assay .
most oseltamivir - resistant viruses in this report were included in the weekly fluview report prepared by cdc ( 6 ) .
we tested a total of 3,652 pandemic ( h1n1 ) 2009 virus isolates and specimens from every state and the district of columbia ; 35 ( 1.0% ) isolates / specimens from a total of 18 states were oseltamivir - resistant ( figure ) .
overall , 8 ( 1.3% ) of 609 isolates tested by ni assay and 27 ( 1.0% ) of 3,043 specimens tested by pyrosequencing were resistant to oseltamivir .
the state - specific prevalence of oseltamivir - resistant pandemic ( h1n1 ) 2009 viruses varied ; however , the number of viruses and specimens tested also varied markedly between states , and several states submitted only a few specimens .
forty - four states submitted > 20 specimens for antiviral resistance surveillance . the prevalence of oseltamivir resistance among these specimens ranged from 0% to 5.6% .
none of the 609 pandemic ( h1n1 ) 2009 isolates tested by ni assay were resistant to zanamivir .
the ranges of 50% inhibitory concentration values for oseltamivir - resistant and -susceptible isolates were 166.17230.37 nmol / l and 0.100.80
geographic distribution of oseltamivir - resistant pandemic ( h1n1 ) 2009 viruses in the united states , october 1 , 2010july 31 , 2011 .
numerators are number of oseltamivir - resistant viruses identified by state public health laboratories ; denominators are number of pandemic ( h1n1 ) 2009positive specimens submitted by each state for susceptibility testing .
the median age of the 35 patients with oseltamivir - resistant pandemic ( h1n1 ) 2009 virus infections was 33 years . of 34 patients with available information ,
26% reported receiving oseltamivir before providing a specimen for antiviral susceptibility testing ( table 1 ) . among 33 patients with a completed case form ,
67% had at least 1 preexisting chronic medical condition , 24% had an immunocompromising medical condition , 42% required hospitalization , and 9% died .
most patients with oseltamivir - resistant virus infection for whom housing information was available lived in a single - family household .
two siblings from 1 household had oseltamivir - resistant virus infection ; neither child had received oseltamivir . * the median age of patients was 33 y ( range 1 mo78 y ) .
nine patients began oseltamivir treatment prior to specimen collection ; none received oseltamivir chemoprophylaxis .  includes hiv / aids , malignancy , autoimmune disorder , solid organ transplant , stem cell transplant , and history of taking immunosuppressive therapy in the past year . 
 includes morbid obesity , obstructive sleep apnea , chronic liver disease , and neurologic or developmental disorders .
all oseltamivir - resistant pandemic ( h1n1 ) 2009 viruses were identified from specimens collected during december 2010april 2011 ; the prevalence of resistance did not change significantly over time ( test for trend , p = 0.18 ) ( table 2 ) .
in addition , the proportion of patients with oseltamivir - resistant virus infections who did not have exposure to oseltamivir before specimen collection did not change significantly over time ( test for trend , p = 0.48 ) ; however , the number of specimens tested each month was small .
the number of oseltamivir - resistant pandemic ( h1n1 ) 2009 virus  infected patients was small during the 200910 ( april 2009september 2010 ) and 201011 influenza seasons .
however , the prevalence of oseltamivir - resistant virus  infected patients was slightly higher during 201011 compared with 200910 ( 35/3,652 [ 1.0% ] vs. 37/6,740 [ 0.5% ] , respectively , p = 0.02 by  test ) ( 2 ) .
also , during 201011 , compared with 200910 , more patients with oseltamivir - resistant virus infection had no history of oseltamivir exposure before specimen collection ( 25/34 [ 73.5% ] vs. 4/35 [ 11.4% ] , respectively ; p<0.0001 by  test ) .
during the 201011 us influenza season , the prevalence of oseltamivir - resistant pandemic ( h1n1 ) 2009 viruses remained low , and most persons with oseltamivir - resistant virus infection had no prior oseltamivir exposure .
this is a notable difference from surveillance findings both globally and in the united states during the 200910 season , when most patients with oseltamivir - resistant pandemic ( h1n1 ) 2009 virus infection had a history of oseltamivir exposure , and many were severely immunocompromised , a condition that may increase the risk for resistance developing during oseltamivir therapy ( 2,7 ) .
these data suggest a low level of community transmission of oseltamivir - resistant pandemic ( h1n1 ) 2009 virus in the united states during the 201011 influenza season .
the united kingdom also reported that the proportion of oseltamivir - resistant pandemic ( h1n1 ) 2009 virus  infected patients without prior oseltamivir exposure was higher during 201011 than 200910 ( 8) .
the increase during the 2010 - 11 influenza season in the proportion of patients with oseltamivir - resistant pandemic ( h1n1 ) 2009 virus infections without prior oseltamivir exposure causes concern in light of the recent history of oseltamivir resistance among seasonal influenza a ( h1n1 ) viruses that circulated before pandemic ( h1n1 ) 2009 virus emerged . in the united states before the 200708 influenza season ,
the prevalence of oseltamivir resistance among seasonal influenza a ( h1n1 ) viruses was < 1% ( 9,10 ) .
however , during the 200708 season , the prevalence of oseltamivir resistance among seasonal influenza a ( h1n1 ) viruses increased to 12% , and by the 200809 season , resistance dramatically increased to > 99% ( 9,11,12 ) .
no association was found between this increase in oseltamivir resistance and prior oseltamivir use ( 11,13 ) .
oseltamivir resistance in pandemic ( h1n1 ) 2009 and seasonal influenza a ( h1n1 ) viruses was conferred by the h275y substitution in the neuraminidase . however , unlike seasonal influenza a ( h1n1 ) viruses , which retained susceptibility to the m2-blocking adamantanes ( amantadine and rimantadine ) , > 99% of circulating pandemic ( h1n1 ) 2009 viruses are inherently resistant to adamantanes ( 14 ) .
thus , inhaled zanamivir or investigational drugs , such as intravenous zanamivir , are the only treatment options for patients with oseltamivir - resistant pandemic ( h1n1 ) 2009 virus infection .
our conclusions are limited by the small number of patients with oseltamivir - resistant pandemic ( h1n1 ) 2009 virus infection .
variability in state surveillance and the number of specimens tested from each state may also have limited the representativeness of our data . despite these shortcomings ,
our findings emphasize the importance of ongoing surveillance for oseltamivir - resistant pandemic ( h1n1 ) 2009 viruses in the united states and globally and of close monitoring for changes in the epidemiology of oseltamivir resistance among pandemic ( h1n1 ) 2009 viruses .
updated information about antiviral resistance in influenza viruses in the united states is available at www.cdc.gov / flu / professionals/.
 during october 2010july 2011 , 1.0% of pandemic ( h1n1 ) 2009 viruses in the united states were oseltamivir resistant , compared with 0.5% during the 200910 influenza season . of resistant viruses from 201011 and 200910 , 26% and 89% , respectively , were from persons exposed to oseltamivir before specimen collection . 
 findings suggest limited community transmission of oseltamivir - resistant virus . 
The Study
Conclusions