Oseltamivir Resistance in Immunocompromised Hospital Patients

According to the latest WHO briefing, there have been two recent clusters of patients infected with oseltamivir-resistant H1N1 viruses reported to the agency. The first cluster occurred in Wales, UK in October 2009, and the second in North Carolina, USA in mid October to November.

Both clusters occurred in a single ward in a hospital in each area, and both involved patients whose immune systems were severely compromised or suppressed. Transmission of resistant virus from one patient to another is suspected in both outbreaks.

The emergence of drug-resistant influenza viruses in severely immunocompromised patients undergoing antiviral treatment is not unexpected, and has been well documented during seasonal influenza. Virus replication can persist in such patients for prolonged periods of time despite antiviral treatment, creating an environment in which drug-resistant viruses can readily be selected.

In the North Carloina cluster, three of the four cases were fatal, but the role of H1N1 infection in contributing to these deaths is uncertain. All of the resistant viruses in both clusters carried the same H275Y mutation, indicating resistance to oseltamivir, but not to the second antiviral drug, zanamivir.

Experts agree that severely immunocompromised patients need to be regarded as an especially vulnerable group, and as early signs of influenza may be masked by symptoms associated with underlying disorders or their treatment, the experts further agreed that doctors treating such patients should operate with a high level of suspicion for influenza virus infection and be especially vigilant for the rapid development of oseltamivir resistance.

In these patients, standard treatment doses and duration for treatment with oseltamivir are unlikely to be sufficient. Though clinical judgement is important, doses may need to be increased and continued, without interruption, for the duration of acute illness. Zanamivir should be considered as the treatment of choice for patients who develop prolonged influenza illness despite treatment with oseltamivir.

Once oseltamivir resistant virus has been detected in a ward treating severely immunocompromised patients, doctors should consider switching to zanamivir as the antiviral drug of first choice for treatment and when considering post exposure prophylactic treatment of other patients on the ward.

Source: WHO Pandemic (H1N1) 2009 briefing note 18 http://www.who.int/csr/disease/swineflu/notes/briefing_20091202/en/index.html