Three of those four patients have died. Health officials say the resistance is due to a mutation in the virus that appears to be happening in isolated cases.
"We don't anticipate at this stage that is going to be a broader issue, but that's what we're going to find out," said Dr. Cameron Wolfe, Duke University Hospital.
The deaths in North Carolina come as the CDC reports a slight decrease in swine flu activity across the country.
"The one thing we know about the flu is that it's really hazardous to try and predict," said L.A. County Director of Public Health Dr. Jonathan Fielding.
Dr. Fielding says flu outbreaks typically come in waves and there could be another deadly spike this spring.
"It is really important that the people in those high risk groups get immunized," Dr. Fielding added. "More vaccines are becoming available. I know that there is still some frustration, but it is starting to ease."
While supply of the vaccine continues to be a problem nationwide, Dr. Fielding says L.A. County has received more than a million doses.
Organizers at a vaccine clinic in Inglewood said Friday that the turnout for the past two clinics has been low.
"I don't think as many people know about this availability as they should," said city of Inglewood spokesman Ed Maddox. "We haven't gotten the word out everywhere. Also there have been a number of news stories indicating that the supply is up and that it is no longer as scarce as it was a few weeks ago."
Health officials are urging people -- especially those in the high risk groups -- to get vaccinated before Thanksgiving, when an increase in travel could cause a spike in flu activity.
The H1N1 vaccination clinic in Inglewood will be open Saturday. The clinic runs from 9 a.m. to 5:30 p.m. at the Hollywood Park Race Track. It's free to individuals in high risk groups.