A mutated strain resistant to the most commonly prescribed drug used to treat swine flu has surfaced in Baltimore, raising concern among experts that the virus could become harder to treat.

The cases of two cancer patients at Johns Hopkins Hospital who contracted the mutated strain are the first involving Tamiflu-resistant H1N1 in Maryland and are among 75 worldwide.

Health officials, noting that the Hopkins patients recovered, say there is no cause for alarm because the cases are isolated and have not spread. But the local cases, diagnosed in October and November, come on the heels of similar mutations found last week in four cancer patients at Duke University Medical Center in North Carolina - three of whom died - and in another cluster of patients at a hospital in Wales.

Dr. Trish Perl, a Hopkins epidemiologist, said hospitals need to be careful about hygiene and watch for new strains, that doctors should prescribe Tamiflu only when necessary, and that the public should get vaccinated against swine flu to avoid transmission.

"Probably, this mutation is out there, so what we want to do is to engage everyone in thinking about this more, particularly the medical community," Perl said. "This is a big wake up call for us. We are going to be more vigilant."

The Hopkins patients were two men who have since been discharged. One was admitted to the hospital after complaining of fever. Doctors tested him for influenza and the sample was sent to the state Department of Health and Mental Hygiene, which has been testing for virus mutations since summer. The other patient was being treated at the hospital and did not get better after taking Tamiflu. Samples sent to the state lab confirmed a mutated strain.

Officials at Hopkins and at the state health department would not disclose more information on the men's conditions, ages or hometowns. Officials said the patients were not likely to spread the virus. The men, who had weakened immune systems which made them more susceptible, were cared for in private rooms by medical staff wearing masks.

Since the H1N1 outbreak last spring, influenza experts have warned that the virus could mutate. In fact, Tamiflu-resistant strains have been found in seasonal flu for several years and made up 98 percent of one seasonal strain last flu season. While it's not surprising that H1N1 would behave in a similar way, drug-resistance is worrisome if such mutations become widespread, limiting the antiviral drugs available to treat disease, Perl said.

While swine flu infections appear to have crested in late October, public health experts are worried about another wave of influenza - either seasonal or H1N1 - once winter sets in. If drug-resistant strains were to spread, they would present a significant challenge, Perl said.

"If we start seeing a lot of resistance, then clinically what we do is, we change the drugs that we use," she said. "That would absolutely impact what should happen if we have another large wave."

Officials are concerned that doctors might be overprescribing antivirals, which can lead to the development of drug-resistant strains.

When prescribed within 48 hours of the onset of symptoms, antiviral medications can reduce the severity of flu and shorten its duration. But Tamiflu is not generally recommended for prevention. In fact, most healthy people will recover after several days of rest.

The medicine, while lifesaving and important, should not be prescribed casually, officials said. The federal Centers for Disease Control and Prevention recommends that people with the flu who are at most risk for complications get first priority for receiving antivirals, including children, pregnant women and those with chronic health problems.

"This is a drug to be taken seriously," said Frances Phillips, the state's deputy secretary for public health services. "For public health, it's an important tool, and we don't want to lose that tool because of overprescribing."

Officials at the CDC and the World Health Organization said this week that drug-resistant strains remain rare. They also note that another antiviral, Relenza, is effective in such cases.

Scientists have been closely monitoring flu cases in the state health department's Baltimore lab and have tested more than 500 samples for evidence of antiviral resistance. Since discovering the drug- resistant strains, officials have sent letters to hospitals and health care providers reminding them to be on the lookout for patients who do not get better after being treated with Tamiflu.

"This, again, is a reason not to take H1N1 lightly," said Phillips. "We want to make sure these resistant strains do not begin transmitting person to person."

Reports of the mutation have health officials repeating this mantra: Get vaccinated. While H1N1 vaccine began trickling into the state early this fall, shipments have increased lately. As of Wednesday, the state had received nearly 1.3 million doses.

"People have gotten a little bit blase about H1N1," Perl said. "But we're finally getting enough vaccine."

Said Phillips: "The bottom line is that there is no reason to think this vaccine would not be effective for any kind of mutation. ... The protection is the vaccine, which is effective and safe and becoming more and more plentiful every day."

Taking antivirals

Recommendations for antiviral medications

* Groups at most risk for complications from the flu should have first priority for antiviral drugs. Those groups include children, pregnant women and people with chronic health problems.

* Patients should be prescribed antivirals within 48 hours of symptoms and take them for five days.

* Use of antivirals should be discouraged in healthy people seeking to prevent flu.

Source: Centers for Disease Control and Prevention

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