Friday, December 20, 2019

"Stop Referring to a Coming Post-antibiotic Era—iI’s Already Here:" Centers for Disease Control

The front face of antibiotic resistance is a problem for medicine. But behind the scenes, the problem of antibiotic resistance becomes a problem of incentives and therefore of economics.

For example, health care providers for a long time had an incentive to under-invest in preventing infections, because after all, it was easy and cheap to cure infections with antibiotics.

In addition, each health care provider individually has an incentive to focus only on the patient sitting in front of them, and whether "just-in-case" or precautionary use of antibiotics might help that patient, while not taking into account the consequence that widespread use of antibiotics will also lead to a rise in infection that are resistant to antibiotics.

Further, the incentives for researchers to seek out and commercialize new antibiotics (or alternative anti-infection treatments) is shaped by incentives for innovation embodied in government support of research and development spending, regulations affecting how soon a new drug can be commercialized, protections for intellectual property, and whether government health care finance would (at least in some cases) be willing to pay a higher price for newly invented anti-infection drugs.

These issues all arise in Antibiotic Resistance Threats in the United States 2019, published by the Centers for Disease Control (November 2019). A substantial portion of the report is given over to estimating the size of the problem, and thus why the CDC concludes that the "post-antibiotic era" is "already here."
More than 2.8 million antibiotic-resistant infections occur in the United States each year, and more than 35,000 people die as a result. The AR Threats Report also includes an estimate of the burden of Clostridioides difficile (C. difficile) infections, because C. difficile is caused by the same factors that drive antibiotic resistance—antibiotic use and the spread of germs. In 2017, nearly 223,900 people in the United States required hospital care for C. difficile and at least 12,800 people died.
To make the message just a little more grim, this issue is a global one. Globalization means that infections with antibiotic resistance can evolve anywhere, and then travel anywhere via people, animals, or even just in the environment.

It's also important to remember that antibiotics themselves can cause adverse drug reactions. (Some of my family members are allergic to just about any drug that ends in -cillin.)
Twenty percent of all hospitalized patients who received an antibiotic experienced an adverse drug event (ADE) as a result. In the community, antibiotic-associated adverse events often require emergency treatment. Among children, antibiotics are involved in 46 percent of emergency department visits for ADEs. Among adults, antibiotics are involved in 14 percent of emergency department visits for ADEs. This amounts to more than 214,000 emergency department visits each year. Because any antibiotic use has the potential to cause harm, clinicians should prescribe their patients these powerful drugs only when the benefits outweigh the potential risks.
Antibiotics definitely continue to make medical sense for specific targeted cases, but they are such a magic wand for fighting infection that they have been overused. "CDC  estimates that U.S. doctors’ offices and emergency departments prescribe about 47 million antibiotic courses each year for infections that don’t need antibiotics. That’s about 30% of all antibiotics prescribed in these settings." Antibiotics have also be used extensively with both pets and feed animals, and on crops as well. But some germs fight back and develop antibiotic resistance.

The possible options fall into a few categories. One is to take as aggressive steps to reduce infections in the first place, so that fighting them isn't needed. Hospitals have become acutely aware of the problem, and there is solid evidence that hospital-acquired infections are declining (although it would of course have been nice if these efforts had ramped up about 20 years earlier). Higher vaccination rates, in the US and around the world, make infections less likely. Just getting everyone to wash their hands a few times each day could make a meaningful difference.

Of course, there's always a hope that we might manage to invent ourselves out of the problem, but while new inventions will help, they aren't likely to be a complete fix. The CDC report notes:
As a result of difficult scientific obstacles and challenging business incentives, many pharmaceutical companies are getting out of the antibiotic business altogether.
  • Between 1962 and 2000, no new major classes of antibiotics were approved to treat common and deadly Gram-negative infections.
  • Since 1990, 78% of major drug companies have scaled back or cut antibiotic research due to development challenges.

In addition, the report provides evidence that there are 42 new antibiotics being researched, but only four have reached the stage of an application to the Food and Drug Administration to allow used of a specific drug. Also, only about one in four of the new antibiotics being researched represent a new class of drugs or a new method of action, and it's clear how well many of the others would address existing antibiotic resistance. The CDC concludes:
With so few novel antibiotics and the number of effective antibiotics dwindling, it is clear we cannot rely on traditional antibiotics alone to treat infections. Alternative antibiotic agents and improved testing are key components to our national healthcare strategy to prevent and treat infections in new ways.
In short, antibiotic resistance is preventing the US healthcare system from saving more than 45,000 lives per year, and it's not going away. The ongoing battle is to use antibiotics only where needed, and find other options wherever  possible, so that antibiotics have as good a chance as possible to keep working where they can do so much good.

Here are some previous posts about the interaction of antibiotic resistance and economics: