Resistance a Growing Problem in Treating Influenza

Bob Roehr

February 06, 2009

February 6, 2009 (Washington, DC) — Management of influenza has become more complicated due to growing resistance to the neuraminidase inhibitor oseltamivir (Tamiflu). That message was a recurring theme here at the Seasonal & Pandemic Influenza 2009 Symposium, sponsored by the Infectious Diseases Society of America.

The influenza outbreak in the United States "so far has been relatively mild in comparison to last season," said Nancy Cox, PhD, director of the Influenza Division at the Centers for Disease Control and Prevention (CDC). Only 2 states, Virginia and New Jersey, have reported a significantly greater number of patients exhibiting flu-like symptoms this season compared with last.

Antiviral resistance is present "in only 1 of the 3 groups of influenza viruses that commonly circulate in people," Dr. Cox said. Resistance in the A strain has emerged "over the past 2 seasons." However, the A strain is the primary circulating virus in the US this year, and about 80% of that is the H1 type, which is resistant to oseltamivir. "Clinicians need to understand this," she said.

Dr. Cox said the strains included in the vaccine for this year are well matched to the strains that are circulating. Influenza season has not yet peaked, she said, and it is not too late to vaccinate patients.

Managing Resistance

Local health departments are responsible for identifying the circulating strains of influenza. "If it is H1N1, we can pretty much assure ourselves that it will be resistant to oseltamivir and that is what has provoked the recommendation from CDC of using 2 antiviral drugs — oseltamivir and rimantadine (Flumadine)," symposium cochair Richard J. Whitley, MD, told Medscape Infectious Diseases. He is a professor of medicine in the Department of Microbiology at the University of Alabama in Birmingham.

"It doesn't preclude the use of zanamivir," he continued. However, there is a contraindication for use of that drug in patients "with bronchospastic disease that are at risk for complications of an inhaled medication." It is also not indicated for use in very young children.

Andrew Pavia, MD, from the University of Utah Medical Center in Salt Lake City, suggested that physicians test to distinguish between influenza A and B. "If it is B, treatment is relatively straightforward; Tamiflu and Relenza (zanamivir) will both work. If it is influenza A, they need to follow the modified guidelines, where roughly half the strains now are H1."

Bacterial Infections

Many deaths associated with influenza infection are caused by bacterial coinfections. "They are causing pneumonia after infection," Dr. Pavia pointed out. Clinicians need to become better at diagnosing and treating the bacterial infection in the face of increased drug resistance, he said.

However, he does not advocate prophylactic administration of antibiotics to prevent pneumonia. Dr. Pavia said, "There isn't any evidence that it does any good, and we have plenty of evidence that they can do harm, including causing very dangerous C difficile infections."

Dr. Pavia said the question of antibiotic use becomes more difficult when a patient "becomes very ill and is hospitalized with what appears to be a bacterial infection. That is where the clinician needs to be aware of what the best choice of antibiotics might be. Right now, the expert consensus is that patients who are critically ill probably should receive drugs that are active against MRSA [multidrug-resistant Staphylococcus aureus]."

Ambulatory patients returning home "as a rule should not receive antibiotics if they have influenza. We don't know about milder cases of what appears to be bacterial pneumonia. Can they be treated with typical agents for pneumonia such as a cephalosporin and a macrolyte, or a quinolone, or should they also receivedrugs that are active against MRSA," Dr. Pavia rhetorically asked.

Pandemic Influenza

The fear of pandemic influenza is that the H5N1 strain will pass from birds to humans and adapt to ready transmission between humans. It also tends to infect young, healthy individuals, unlike common influenza, which tends to infect the very young and the very old.

The number of incidents of transmission to humans has remained small, only 16 people in Asia during this current season. Most of those infected were directly involved with handling wild fowl. Evidence of human-to-human transmission is scant.

While significant progress has been made in developing human vaccines for H5N1, they require use of an adjuvant and 2 separate inoculations. There are currently no plans to include those components in the seasonal vaccine, said Arnold S. Monto, MD, cochair of the symposium and professor in the Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor.

Human H5N1 vaccines are being placed in stockpiles for the purpose of trying to contain an outbreak of pandemic influenza should it emerge. However, vaccines have a limited shelf life and as they approach their expiration date there will be increased discussion on whether to use stockpiled H5N1 vaccine in select populations. With little evidence of H5N1 disease in humans, the risk benefit currently tilts against use.

However, "All we have to have is a few cases of highly pathogenic avian influenza in our fowl population in North America and you will see that Americans will demand that there be a vaccine they can take under those circumstances," said Dr. Whitley.

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