Two American campers developed Tamiflu-resistant swine flu earlier this summer, the best evidence to date that resistant pandemic viruses may have passed from one person to another, the U.S. Centers for Disease Control reported Thursday.

Viruses from both campers contained a mutation that hasn't been seen before with the pandemic virus, a finding that heightens suspicions that drug resistant virus was either transmitted from one child to the other or that both were infected by someone else who wasn't turned up in the investigation.

The previously identified cases of Tamiflu-resistant swine flu viruses have been isolated -- people who took the drug, either for prevention or treatment. There was one exception: a girl from San Francisco who hadn't taken the drug and therefore must have caught a resistant virus from someone else. The source was never identified.

"These are a bit different in that they were linked to each other, which suggests that resistant virus was likely either transmitted to both of them from somebody else or transmitted from one to the other," Dr. Zach Moore, a respiratory disease epidemiologist with the North Carolina division of public health in Raleigh, said of the campers.

Moore was one of the authors of the study, which was published Thursday in Morbidity and Mortality Weekly Report, the CDC's weekly fast-track public health journal.

Moore said there is also a possibility that resistance developed independently in both of these campers. But the presence of the new mutation in viruses found in both girls makes that option seem less likely, said Dr. Frederick Hayden, a leading antiviral expert at the University of Virginia.

"It does serve as another ... marker to suggest that the virus that the two girls had might be the same one," Hayden said when asked to comment on the report. He was not involved in the investigation.

The CDC said the function of the new mutation, at position 223, isn't yet known.

But Hayden said a similar mutation has been reported in the H3N2 seasonal flu virus. In H3N2, the 223 mutation isn't enough to trigger resistance on its own. But when found in combination with another mutation -- which the North Carolina viruses had -- it further reduces response to the drug.

The report brings to 21 the number of known cases of novel H1N1 resistance to oseltamivir or Tamiflu, said Charles Penn, an antiviral expert with the World Health Organization. Those cases have occurred in Denmark, Japan, China (on the mainland and in Hong Kong), Canada, the United States and Singapore.

Penn said all those viruses were sensitive to zanamivir or Relenza, a drug in the same class as Tamiflu.

The camp outbreak occurred in July and it appears that if there was spread of resistant viruses there, the chain of transmission was subsequently broken.

"There's no evidence that this has become widespread," Moore said, noting his department sent a larger than normal number of viruses to the CDC for drug susceptibility testing after the outbreak to see if there might be spread elsewhere in the state.

Of 59 viruses checked, none carried the mutation known to render these viruses resistant to Tamiflu. And none carried the additional mutation seen in the viruses from the campers.

The adolescent girls shared a cabin and both developed swine flu despite being given the drug on a preventative basis. The camp they were attending was experiencing a large swine flu outbreak and over 400 campers and nearly 200 staff members were given Tamiflu or Relenza to try to prevent infection.

An editorial commentary following the article noted these cases underscore the importance of not giving healthy people oseltamivir -- sold as Tamiflu -- to prevent infection after they've been exposed to the pandemic virus. Using the drug to prevent infection is called prophylaxis.