Preliminary tests reveal that the dominant flu strain in the country mostly is resistant to the leading drug used to treat it, public health officials say.
Tamiflu, the most commonly used "anti-viral" drug -- one that many families have stockpiled against an outbreak of the much-feared "bird flu" -- seems ineffective this year against treating the most common form of influenza.
Doctors are struggling to understand why 99 percent of the H1N1 flu strain no longer responds to Tamiflu.
"This is unnerving. It's not as though we overused Tamiflu, but there was a mutation and all of a sudden this strain became the dominant strain all over the country," said Dr. William Schaffner, chairman of Preventative Medicine at Vanderbilt University Medical Center.
It is not unusual for the odd flu strain to become resistant to Tamiflu. What is unusual, and so concerning to doctors, is that a drug-resistant strain has become the most common flu strain that is making people sick.
"Now that we don't have a drug to easily treat them, there will be more hospitalizations. And yes, there could be more deaths," Dr. Greg Poland of the Mayo Clinic told ABC News.
And to make matter worse, said Poland: "This particular strain that we're talking about has an increased propensity to cause pneumonia in the people it infects. So we sort of have a double whammy."
The Centers for Disease Control has warned doctors not to use Tamiflu unless local labs indicate the influenza in their specific community will actually respond to the drug.
But that can be an issue in rural areas or in emergency rooms where that level of diagnostic testing is not readily available. Anti-virals must be administered with the first 48 hours after symptoms begin.
The only well-tested alternative to Tamiflu is the anti-viral drug Ralenza, which is a "dry powder inhaler" that many patients find difficult to use. Some people are told not to use it at all, including people with chronic respiratory conditions like asthma, pregnant women and children younger than age 7.
Less than 10 percent of flu patients each year are treated with an anti-viral drug. In most cases, the case of flu gets better on its own. But doctors emphasize that those who are prescribed a medication are the sickest of patients who need an effective anti-viral.
On average, 36,000 Americans die from the flu each year in the United States, according to the CDC, and more than 200,000 are hospitalized.
Fortunately, this flu season, which typically begins in the U.S. in November and lasts through March, is off to a mild start. According to the Centers for Disease Control, no state has yet reported widespread influenza outbreaks.
But doctors warn that could change at any time. With the leading flu treatment now ineffective, doctors say the focus should be on flu prevention. And this is one year when there is an ample supply of flu vaccine.