resistance, page-11

Comments: Much of what is below has been posted already. It does look like they are becoming more diligent with regard to testing for resistance with a much larger sampling programme.




ECDC DAILY UPDATE

Pandemic (H1N1) 2009 Update 23 November 2009, 09:00 hours CEST

Main developments in past 72 hours

Two clusters of possible transmission of oseltamivir resistant Pandemic Influenza A(H1N1)v among hospitalized patients, United Kingdom and United States

UK: Nine Pandemic Influenza A(H1N1)v confirmed cases have been reported amongst patients on a hospital ward in Wales.[3] Five of these cases are determined to be resistant to oseltamivir, one is sensitive and for three resistance status is currently unknown. The cluster is in a group of patients with haematological problems which result in immuno-suppression either because of the disorder or the chemotherapy given to treat the disorder. Although further epidemiological investigation is underway, it would seem likely that transmission of oseltamivir-resistant H1N1 virus has taken place.

Further follow-up of cases and their close contacts both on the ward and in the community is underway to ascertain if there is evidence of transmission.

The virus remains sensitive to the other licensed neuraminidase inhibitor zanamivir which is being used as an alternative antiviral and to which patients are responding.


USA: Four patients at a hospital in North Carolina who developed influenza in October were found to have oseltamivir resistant pandemic influenza A(H1N1) [4]. The cluster was detected when the patients did not respond to oseltamivir treatment. Three of the four patients have died. All of the patients were located in a ward for people with cancer or severe blood disorders. All were severely ill and were highly susceptible to infections.

Preliminary genetic evidence suggests that the virus spread among patients at the hospital.

The U.S. Centers for Disease Control and Prevention (CDC) is testing virus samples from the patients at Duke to see whether they're indistinguishable from one another.

In addition to investigating the hospital cluster, state and federal epidemiologists are trying to determine whether oseltamivir resistant influenza is circulating elsewhere in North Carolina.


ECDC comment:

Oseltamivir resistance to influenza viruses is well documented in immunosuppressed individuals and can develop quickly if oseltamivir is being given. It is likely to be associated with the high viral load which may occur during infection in these patients. In addition, immunosuppressed people may be more susceptible to infection (i.e., a smaller exposure may result in infection in these patients). It is thus not surprising that spread of resistant virus may occur from patients in whom resistance is more likely to develop during treatment to patients who are very susceptible, especially in a confined setting such as a hospital ward.

The range of manifestations (e.g., asymptomatic, mild, severe) of influenza infection, such as observed with the 2009 A(H1N1) pandemic, makes it difficult, if not impossible, to determine if any given patient or healthcare worker is carrying virus. Thus, people in contact with an index patient can innocently spread influenza to other patients.

Unvaccinated healthcare workers and visitors in contact with these patients may be at risk for being infected with this resistant strain. At this time it is difficult to predict the likelihood of spread of this resistant strain into the community through these people or another means. The conditions under which these clusters occurred are likely to be present at other medical centres throughout the EU. That is, transmission of influenza in the community with immunocompromised patients in healthcare settings receiving either prophylactic or therapeutic oseltamivir.

Thus, member states should remain vigilant for similar clusters now and in the future. Unless oseltamivir resistance becomes more common, it remains appropriate to use oseltamivir for the treatment and prophylaxis of influenza in the UK, the US and elsewhere. Treatment failure is a reason to consider alternative treatment and to test a viral isolate for resistance.

The continuous surveillance for resistance from a sample of isolates taken from community infections should be maintained in countries where resources for testing are available.

Countries without resistance testing capacity should send samples elsewhere for testing on a periodic basis. The best ways to prevent the spread of antiviral susceptible and antiviral resistant influenza in the healthcare setting and between healthcare settings and the community is to ensure healthcare workers are immunized and that there is strict adherence to infection control procedures.


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