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Victories over continually evolving pathogens are often fleeting at best. No sooner do researchers release a new generation of antibiotics or antivirals, than these organisms begin to find ways to work around them.
Maryn McKenna’s terrific book Superbug: The Fatal Menace of MRSA goes into great detail about the road to antibiotic resistance, but we are seeing a similar path being followed by antivirals as well.
Amantadine managed to remain an effective treatment and/or prophylaxis against influenza A for four decades, although it was used only sparingly for the first 30 years or so.
Overuse of Amantadine, particularly its inclusion into chicken feed during the 1990s to combat bird flu in Asia – has been credited with a dramatic rise in influenza’s resistance to the drug by 2005.
Tamiflu (oseltamivir), released in 1999 proved extremely effective against influenza until 2008, when a resistant version of seasonal H1N1 appeared and quickly spread around the world. Seasonal H3N2 remained susceptible to the drug.
These two seasonal viruses have been (at least temporarily) replaced by novel H1N1, which fortunately remains sensitive to the drug. Scientists do worry that over time, novel H1N1 could pick up resistance to Tamiflu as well.
Which brings us to a report issued yesterday by the NIH about two patients that developed resistance to Tamiflu, and in one case, to the newly approved peramivir.
FOR IMMEDIATE RELEASE
Friday, March 26, 2010Media Contact: Anne A. Oplinger
(301) 402-1663
niaidnews@niaid.nih.govRapid Development of Drug-Resistant 2009 H1N1 Influenza Reported in Two Cases
Reevaluation of Treatment Strategies for Prolonged Infection Urged
Two people with compromised immune systems who became ill with 2009 H1N1 influenza developed drug-resistant strains of virus after less than two weeks on therapy, report doctors from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. Doctors who treat prolonged influenza infection should be aware that even a short course of antiviral treatment may lead to drug-resistant virus, say the authors, and clinicians should consider this possibility as they develop initial treatment strategies for their patients who have impaired immune function.
Both patients in the new report developed resistance to the key influenza drug oseltamivir (Tamiflu), and one also demonstrated clinical resistance to another antiviral agent, now in experimental testing, intravenous peramivir, note senior authors Matthew J. Memoli, M.D., and Jeffery K. Taubenberger, M.D., Ph.D. This is the first reported case of clinically significant peramivir-resistant 2009 H1N1 illness, say the scientists. The report is scheduled to appear in print on May 1 in Clinical Infectious Diseases and is now online.
The people in the current case report had immune limitations due to blood stem cell transplants that occurred several years previously. Both recovered from their influenza infections.
“While the emergence of drug-resistant influenza virus is not in itself surprising, these cases demonstrate that resistant strains can emerge after only a brief period of drug therapy,” says NIAID Director Anthony S. Fauci, M.D. “We have a limited number of drugs available for treating influenza and these findings provide additional urgency to efforts to develop antivirals that attack influenza virus in novel ways.”
The 2009 H1N1 influenza virus is susceptible to just one of the two available classes of anti-influenza drugs, the neuraminidase inhibitors. Besides oseltamivir, other neuraminidase inhibitors are zanamivir (Relenza), which is inhaled, and the intravenously administered investigational drug peramivir. As the H1N1 influenza pandemic unfolded, laboratory tests of virus strains isolated from patients showed that some strains contained a genetic mutation (the H275Y mutation) that makes the virus less susceptible to some neuraminidase inhibitors.
Lisa Schnirring at CIDRAP News has more details on this story.
Researchers report peramivir-resistant H1N1 case
Lisa Schnirring
Staff Writer
Mar 26, 2010 (CIDRAP News) – Researchers today sounded two warnings for clinicians who manage pandemic H1N1 patients: that even a short course of oseltamivir (Tamiflu) can lead to antiviral resistance and that patients can develop resistance to peramivir, an alternative to oseltamivir in emergency situations.
The warnings come from a case report of two patients published today in an early online edition of Clinical Infectious Diseases (CID). The authors are from the National Institute of Allergy and Infectious Diseases (NIAID) and the US Food and Drug Administration (FDA). The study is scheduled to appear in the May 1 issue of CID.
The research team, headed by senior authors Matthew J. Memoli, MD, and Jeffery K. Taubenberger, MD, PhD, said the report details the first clinically significant peramivir-resistant pandemic H1N1 case.
These are, admittedly, isolated incidents.
And it should be noted that these two cases involved spontaneous resistance forming in immune compromised patients receiving Tamiflu, and are not due to some new Tamiflu/peramivir resistant strain circulating in the wild.
The takeaway message from this report isn’t that these drugs are losing effectiveness, but that resistance can develop quickly in rare instances in some people receiving these medications.
Which is another good reason why getting a flu shot every year is an exceedingly good idea.
While not 100% protective, getting the flu shot can significantly reduce your chances of catching the flu.
After all, it is better to try to prevent an illness, than to have to treat one.
