Two cases of Tamiflu-resistant swine flu have been found in the United States, in leukemia patients who were highly immunosuppressed, the U.S. Centers for Disease Control reported Friday.
The cases, both from Seattle, are not linked. And there is no evidence either person transmitted drug-resistant pandemic viruses to either the health-care workers looking after them or their personal contacts.
But the findings underscore the reality that people who are highly immunocompromised and who contract the novel H1N1 virus could generate and spread drug resistant variants of the pandemic virus.
"That's a legitimate public health concern," said Dr. Frederick Hayden, an antiviral expert at the University of Virginia.
These are the first cases of Tamiflu-resistant swine flu found in the United States, though not the first to arise there. Last month it was reported that an California teenager quarantined with swine flu immediately after arriving in Hong Kong was found to be infected with a Tamiflu-resistant strain. She contracted the flu before leaving San Francisco, where she lives.
These new cases highlight the catch-22 of treating pandemic influenza in people who are severely immunosuppressed. These patients should be given flu drugs because their immune status leaves them highly vulnerable to severe illness. But giving them the drugs raises at least the theoretical risk that they will develop and spread antiviral resistant strains of the novel H1N1 flu.
It has been shown with seasonal influenza viruses that people with suppressed immune systems -- either from birth, disease or because they are taking anti-rejection drugs following transplant surgery -- can have prolonged viral replication when they get sick with flu.
Studies suggest such patients can shed viruses for weeks and even months.
If they are taking antiviral drugs, the longer they shed viruses, the more likely they are to develop resistance to the drugs. And if they develop drug resistance, they could -- at least in theory -- transmit those resistant viruses to others.
An influenza expert with the CDC said given what's known about flu in immunosuppressed patients, officials are not surprised to see cases of resistance to oseltamivir (Tamiflu's generic name) in this patient population.
"It's not unexpected," Dr. Tim Uyeki said in an interview from Atlanta.
"And it is important for clinicians, family members, caregivers to be aware ... that there is potential for prolonged viral shedding and antiviral resistance to develop in (severely immunocompromised) patients with novel H1N1 virus infection."
Hayden went further, saying it would actually be surprising if cases of drug resistance weren't spotted in highly immunocompromised patients with pandemic H1N1.
"These are the kinds of hosts (patients) where you would really anticipate for drugs -- whether it's for flu or other viral infections -- that resistance emergence is going to be a problem," he said.
Uyeki said when patients like these come down with flu, they would be tested virtually weekly to see whether they are still shedding viruses and whether they have developed resistance to the medication with which they are being treated.
Health-care workers and contacts of the two patients have been investigated and there is no sign of spread of resistant viruses beyond the two patients, he said.
One case involved a male teenager with leukemia who received a stem cell transplant in early May. While recovering in hospital in a single room he contracted swine flu. It's unclear whether he was infected by a visitor or a member of the hospital staff.
"It's unknown how that infection was acquired," Uyeki said.
That patient has recovered. But the second case, a woman in her 40s, remains in hospital. She also has leukemia and had a stem cell transplant late last year. This spring she went through two rounds of immunosuppressive chemotherapy.
The woman is being treated with an intravenous form of the only other flu drug available, Relenza and another antiviral drug, ribavirin.
Uyeki said the CDC isn't changing its guidance on antiviral treatment as a consequence of the findings.
The agency recommends people who contract pandemic influenza be treated with either Tamiflu or Relenza if they are hospitalized or if they are at high risk of becoming seriously ill because they are pregnant or have a disease known to complicate recovery from flu.
But Uyeki said if there is evidence of Tamiflu resistance or even if it is suspected because a hospitalized or high-risk patient isn't recovering, Relenza should be used if it is available and the patient can tolerate it.
Since the pandemic began, 11 cases of Tamiflu resistance have been reported. Three of those were reported Friday -- the two in Seattle and a new case in Hong Kong.
Japan and China have each reported three. In the case of China, one case occurred in Hunan province on the mainland and two in Hong Kong. Canada, Denmark and Singapore have each found one.
Most of these cases have occurred in people who took the drug as treatment for swine flu or to prevent infection with swine flu.
The sole exception so far is the case of the California teenager who travelled to Hong Kong. She had not previously taken Tamiflu, suggesting she was infected from the start with a resistant virus. The source of her infection was not found and no other cases of resistance have been reported from the San Francisco area, where she lives.
