Concerns for Flu-Drug Resistance Grow

We’re in the middle of influenza season and flu activity is still high in the United States, with the proportion of outpatient visits for influenza-like illness at 3.8%—above the national baseline of 2.2%— for the week ending January 26, 2019. The US Centers for Disease Control and Prevention (CDC) reported that influenza A(H1N1)pdm09 continues to be the predominant flu virus this year across the country.

Although many individuals might reach for anti-viral medications in the face of an influenza infection, there is growing concern about resistance to flu medication stemming from a recent finding by Japanese researchers.

Microbial resistance is not reserved solely for bacteria and antibiotics; the truth is that viruses are wholly capable of mutating to become resistant against medications. Consider HIV—the virus has the ability to mutate and continue viral production in the presence of the antiretroviral drugs that are used to kill it. The same concerns exist for influenza viruses, which already mutate quite rapidly.

In late January, investigators published findings that a new influenza antiviral drug may not be as effective as originally anticipated. Marketed as a competitor for existing medications Tamiflu (oseltamivir) and Relenza (zanamivir), this new medication is called Xofluza (baloxavir marboxil) and is recommended for flu treatment. Although Xofluza doesn’t prevent the flu like the vaccine, if taken within 48 hours of becoming sick with symptoms, such antiviral drugs can help lessen the symptoms and shorten the duration of sickness. The driving point of Xofluza is that it is offered as a single dose while Tamiflu requires twice daily doses for 5 days.

Although Xofluza was approved by the US Food and Drug Administration in October 2018, investigators in Japan (where it had been approved January 2018) found that influenza A(H3N2) viruses were exhibiting a reduced susceptibility to the drug, meaning that its efficacy was being called into question. The investigators found that patients with the dual infection of influenza A(H1N1)pdm09 and A(H3N2) strains had prolonged periods of viral shedding and those who had received the drug exhibited symptoms for longer periods of time. Investigators noted that “our findings indicate that these viruses emerged under the selective pressure of baloxavir marboxil. In contrast, no viruses exhibiting reduced susceptibility to NA inhibitors were detected among 90 influenza A viruses tested between September and December 2018 in Japan. Therefore, the baloxavir susceptibility of influenza viruses should be closely monitored.”

American investigatora also are keeping an eye on baloxavir susceptibility and assessed it against influenza viruses that were circulating in the United States during the 2016-2017 and 2017-2018 flu seasons. Their efforts not only worked to establish a surveillance and testing methodology for monitoring susceptibility but also found that, although there was some reduced susceptibility in the 2016-2017 season (albeit low), there was none in the 2017-2018 season.

The findings by the US research team are relieving and provide hope for the efficacy of the new flu drug. However, the findings of the Japanese research team should encourage us to continue to watch flu susceptibility closely. Moreover, Xofluza is a new drug to the market and although the single-dose is an advantage, it is also more costly for patients. The current goal is to find a universal flu vaccine, which would alleviate some of the dependence on antiviral medications for flu. These findings should be a stark reminder that antimicrobial resistance is not limited to bacteria.