WHO: Resistant flu clusters warrant greater vigilance, treatment tweaks

Dec 2, 2009 (CIDRAP News) – The World Health Organization (WHO) said today that oseltamivir (Tamiflu)-resistant pandemic H1N1 cases in hospital settings suggest that treatment doses may need to be increased in immunocompromised patients who have flu symptoms.

The agency made this statement after a teleconference with experts about two recent clusters of resistant cases. It also concluded that the events don't signal a public health threat.

The WHO, in a statement, said emergence of drug-resistant flu in severely immunosuppressed or immunocompromised patients is expected and has been well documented in seasonal flu.

In late October a Welsh hospital detected an outbreak of oseltamivir-resistant pandemic H1N1 in eight patients who had severe hematologic disorders. Edwina Hart, health minister for the Welsh Assembly Government, said today in a statement that three of the patients appear to have been infected in the hospital.

Three are still hospitalized, one in critical care. All are responding to treatment with a different antiviral, she said.

Hart said so far there is no evidence that the resistant strain spread outside the hospital and that it does not appear to be any more severe than nonresistant strains.

In the United States between mid October and early November, four cases occurred in severely immunocompromised patients who were hospitalized at Duke University Medical Center in North Carolina. Three of the patients died, but officials aren't sure what role the pandemic H1N1 virus played in their deaths.

The hospital said in a statement today that extensive testing and screening by the US Centers for Disease Control and Prevention, along with the state and the university, have shown no other cases of oseltamivir-resistant pandemic flu so far. Daniel Sexton, MD, an infectious disease specialist and director of the Duke Infection Control Outreach Network, said more work is under way to better understand the nature of the four cases.

The WHO said investigations at the two hospitals are reassuring and that the resistant virus has not been detected in any staff caring for the patients, which suggests that it doesn't spread easily to otherwise healthy people, particularly when good infection controls are in place. It said surveillance found no spread to other hospital wards or the wider community.

Experts participating in the WHO's conference call emphasized that severely immunocompromised patients are especially vulnerable to infection, difficult to treat, and more likely to develop resistance, the agency said. They urged physicians to be extremely vigilant with these patients, because their underlying conditions or treatment may mask early flu symptoms and oseltamivir resistance can develop rapidly.

Though clinical judgment is still key, doctors who treat immunocompromised patients for flu symptoms may need to increase the oseltamivir dose and continue it without interruption during the course of acute illness, the WHO said.

Once physicians detect oseltamivir-resistant pandemic H1N1 in a ward treating these vulnerable patients, they should consider switching to zanamivir as the drug of choice for treatment and prophylaxis.

Experiences with oseltamivir-resistant seasonal H1N1 show how quickly the strains can spread and become established, and neuraminidase inhibitors have improved clinical outcomes in patients with severe pandemic flu, the WHO stated. "This experience underscores the need to protect the effectiveness of these drugs by minimizing the occurrence and impact of drug resistance."

Over the past 2 weeks the number of documented oseltamivir-resistant H1N1 cases has risen from 57 to 96, in line with recent increases in global pandemic activity and a resulting increase in use of the drug, the WHO reported. About a third of the cases occurred in patients who had hematologic malignancy, were undergoing chemotherapy, or were undergoing post transplant treatment.

"The clusters in the two hospital wards should be viewed in the context of these overall trends," the WHO said, adding that though all oseltamivir-resistant cases warrant investigation, there's no evidence that they are a public health threat.

See also:

Dec 2 WHO pandemic briefing note

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