# 5125
The old adage - `if you make a better mouse trap, nature will begin to work on a better mouse’ - is well illustrated by the continual evolution of bacteria and viruses to evade our arsenal of antibiotic and antiviral agents.
Between MRSA and the growing number of emerging carbapenemases - antibiotic resistance (rightfully) has most of our attention because it directly impacts tens of thousands of patients every year.
Antiviral resistance – for now – is viewed with somewhat less alarm simply because we are not currently in an influenza pandemic, and it is rare that we encounter an influenza virus that is resistant to our entire arsenal of antiviral drugs.
But scientists worry that could change.
A few short years ago Amantadine (an M2 ion channel blocker) was the preferred influenza antiviral. It was cheap, plentiful, and worked pretty well.
But by the mid 2000s Amantadine began to lose its effectiveness against the H3N2 seasonal flu virus and some strains of the H5N1 bird flu.
It has been suggested that the prophylactic use of Amantadine by Chinese poultry farmers (who supposedly included it in their chicken feed for several years) may have contributed to this sudden resistance.
But whatever the cause, by January of 2006 the CDC had issued a warning to doctors not to rely on Amantadine (or Rimantadine) to treat influenza.
Oseltamivir (Tamiflu) – a newer neuraminidase (NA) inhibitor drug introduced in 1999 - while far more expensive, became the new treatment standard.
But within two years seasonal H1N1 began to show growing resistance to Oseltamivir as well (although H3N2 remained sensitive).
By the spring of 2009, - in the space of just about a year – seasonal H1N1 had gone from almost 100% sensitive to the drug to nearly 100% resistant.
The arrival of a novel H1N1 pandemic virus was a game changer, in that it – unlike seasonal H1N1 – was still sensitive to oseltamivir (but not Amantadine).
In short order novel H1N1 supplanted the seasonal strain, breathing new life – at least for now – into the neuraminidase (NA) inhibitor class of antivirals.
But over the past 18 months we have seen a small number (less than 2% of samples tested) of Oseltamivir resistant novel H1N1 viruses – along with some evidence of transmissibility.
So the concern lingers. If seasonal H1N1 could go from nearly completely susceptible to completely resistant to oseltamivir in a year’s time – could it happen again with the new H1N1 strain?
And if that happens, what antiviral alternatives do we have in the pipeline?
These issues are addressed in the January issue of IDSA’s Journal of Infectious Diseases in a pair of articles and an editorial.
First, links to the three JID items, followed by excerpts from the IDSA’s press release.
“Dual Resistance to Adamantanes and Oseltamivir Among Seasonal Influenza A (H1N1) Viruses: 2008-2010”
“Evidence of Person to Person Transmission of Oseltamivir Resistant Pandemic Influenza A (H1N1) 2009 Virus in a Hematology Unit”
A few excerpts from the accompanying press release:
Influenza Virus Strains Show Increasing Drug Resistance and Ability to Spread
Studies Highlight Need for New Antiviral Treatment Options and Strategies
Two new studies raise public health concerns about increasing antiviral resistance among certain influenza viruses, their ability to spread, and a lack of alternative antiviral treatment options. The findings are published in the January 1 issue of The Journal of Infectious Diseases.
(Please see
below(above) for links to these articles online.)
Influenza viruses are treated with two classes of drugs: M2 blockers (adamantanes) and neuraminidase inhibitors (NAIs), including oseltamivir and zanamivir. While the spread of influenza strains with resistance to one class of drugs has been well documented in recent years, a new report from Larisa Gubareva, MD, PhD and colleagues at the Centers for Disease Control and Prevention (CDC) and at health agencies in West Virginia, Texas, and Canada, confirms that dual resistance can emerge in several ways and has been on the rise during the past three years.
<SNIP>
Although dual resistant viruses are still rare, the investigators noted an increase in the number of tested viruses with this resistance, from 0.06 percent (2007-2008) to 1.5 percent (2008-2009) to 28 percent (2009-2010); however, during the 2009-2010 season the number of circulating seasonal H1N1 viruses was low, and only 25 viruses were tested. “Because only two classes of antiviral agents are approved, the detection of viruses with resistance to drugs in both classes is concerning,” said Dr. Gubareva. “If circulation of viruses with dual resistance becomes more widespread among any of the predominant circulating influenza A viruses, treatment options will be extremely limited. New antiviral agents and strategies for antiviral therapy are likely to be necessary in the future.”
