Antibiotics Are Becoming Less Effective. Here's Why.

Antibiotics, credited with saving millions upon millions of lives over the 20th and 21st centuries and increasing the average American's life expectancy by up to a decade, are facing a rising tide of infectious bacteria that are resistant to their effects. One of the most revolutionary achievements in medicine and public health is under threat.

Signs of this looming peril keep popping up. The Centers of Disease Control and Prevention reported this month that the prevalence of antibiotic-resistant gonorrhea, which is only treatable with two types of antibiotic, has risen.

In May, a woman in Pennsylvania presented with an infectious microbe with a particularly resistant gene that "heralds the emergence of truly pan-drug resistant bacteria," according to the scientists who made the finding.

"The resistant threats that we see today are bacteria that can be resistant to nearly every antibiotic that would be considered for treatment," said Dr. Jean Patel, director of the Office of Antimicrobial Resistance with the CDC.

"This is not a problem that we had in the past. This is a new problem," she continued. "We’ve fallen into a bit of complacency that these drugs would always be around and always be active."

What would the world look life if the number of antibiotic-resistant infections become common?

Many run-of-the-mill nuisances like urinary tract or sinus infections could persist much longer than they do now, causing much more pain and damage than they do when they're quickly treated with antibiotics. Some of these infections could spread to the kidneys or brain and become life-threatening.

Common surgical procedures — cesarean sections, hip replacements, colonoscopies, heart surgeries — make the body susceptible to potentially deadly bacteria, and patients are often pre-treated with antibiotics prior to these procedures. If antibiotics become unreliable or ineffective, many of these procedures would be much higher risk.

Research has found that antibiotics save 200,000 lives in the United states every year, and that doesn't even count those whose lives would be severely disrupted or become disabled.

But what is causing antibiotic resistance? And what can be done to stop it?

The causes

Antibiotics work in different ways to kill infectious bacteria. Penicillin, for example, works by breaking down the cell walls of the microbes, causing them to burst.

Other antibiotics work through different mechanisms; no matter how they work, though, there's always a minority of bacteria that, because of natural variation, are immune to the drug's effects.

As antibiotics get used more frequently, these minority bacteria get the best chance to thrive. So just by using antibiotics, we will inevitably create some antibiotic resistance, as demonstrated in this illustration from the Centers for Disease Control and Prevention:

Bacteria also have the ability to pass pieces of their DNA to other bacteria, including other species. When the DNA exchanged contains drug-resistant genes, more bacteria become immune to our most important treatments.

These effects are inevitable whenever antibiotics are used, but they are greatly exacerbated by the misuse of antibiotics.

There are three main types of antibiotic misuse:

• Unnecessary antibiotic use
• Incomplete antibiotic use
• Antibiotic use in animal farming

Unnecessary use is extremely common, because many people request antibiotics even when they won't help, and doctors often comply.

"In hospitals, the inappropriate use of antibiotics can be as high as 50 percent," said Patel.

It always feels nice to receive treatment. But many common ailments, like colds and flus, are caused by viruses, which are entirely unaffected by antibiotics. Using them in these instances just increases the chance of resistance developing in the bacterial population, without providing any tangible benefits.

"I think we’ve fallen into a bit of complacency that these drugs would always be around and always be active," said Patel. "Now that we’re starting to see antibiotic resistance emerge, it’s clear that we need to be very careful when we use antibiotics, and only use them when we absolutely have to."

Other challenges arise from the incomplete use of antibiotics. Sometimes, a course of antibiotics will be prescribed to be taken every day for a week or longer, but the patient starts feeling better after the first few doses, so they stop taking the drugs.

While this might seem prudent given the problems with overuse, this actually gives the bacteria an advantage. With a low dose of antibiotics, bacteria with weak resistance to the drug may survive. And if this population multiplies, genes that are strongly resistant are more likely to emerge and proliferate.

So it's best for patients to take a complete course of any antibiotics prescribed, so that the bacteria don't have this opportunity. But ensuring that patients follow through with the treatment is particularly tricky with very long courses of antibiotics, such as those needed to treat tuberculosis, which may take several months to complete.

The other big misuse of antibiotic occurs not in humans but in animals.

"Basically, farmers can buy this stuff over-the-counter," said Polly Price, professor of law and global health at Emory University.

Because farmers keep animals in cramped and crowded conditions, infections can become rampant. So they make liberal use of antibiotics as a preventive measure against the spread of bacteria; antibiotics are also used to promote growth in the animals. These practices only raise the risk of antibiotic resistance developing and spreading to humans.

At present, there is only limited regulation on farmer's use of antibiotics.

What's being done about it?

"The most pressing matter is to have tighter regulations on use in animals," said Price. "Any ways we could restrict antibiotic use in livestock is key."

Patel notes that the use of antibiotics for growth promotion in animal agriculture is being phased out. There are some existing legal programs that try to enforce "judicious use" of antibiotics on farms, and policymakers are considering further regulations of the industry.

But off the farm, few legislators are enthusiastic about pressing for greater control over antibiotic distribution.

"People are very hesitant to interfere in the doctor-patient relationship in anyway that would actually limit the use of antibiotics as a legal matter," said Price.

There are alternatives to using the blunt force of the law to stop inappropriate use of antibiotics. Experts can monitor the prescription rates, and some hospitals use "antibiotic stewardship" programs to regulate and control their own practices.

By tracking this data, the CDC has found that there are large geographical differences in the practice of prescribing antibiotics across the country. Educational efforts that teach both patients and doctors that antibiotics are often unnecessary and should be used very judiciously, specifically targeting those regions that a more liberal in their prescription practices, can and must be effective at reducing rates of overuse, Patel said.

But Patel also believes education is not enough. New, rapid diagnostic tests, which could quickly confirm the source of an infection, could significantly reduce inappropriate antibiotic use. If doctors are able to know for sure that an infection is caused by a virus, or it's caused by a specific kind of bacterium that responds best to one kind of antibiotics, then it would be much easier to ensure only proper treatments are prescribed.

"We [the United States] actually do a much better job, at least in terms of requiring prescriptions," said Price. "There are many countries, in fact most of central and south America, [where antibiotics] are available over the counter."

This means many people in these countries simply self-prescribe antibiotics without ever seeing a doctor. Price warned that because of these practices, there's a high risk of antibiotic resistance developing outside of the United States.

The search for new antibiotics

The most natural response to growing antibiotic resistance is that we need more antibiotics.

But Patel warned that this line of thinking is overly simplistic.

"There are new antibiotics in development, but there are never enough," she said. "And the drugs that are in development all have some holes in their coverage. That means for the infections they’re going to treat, there will be bacteria that either are not treated, because the drug has a limited spectrum of activity, or there’s already resistance in bacteria that is causing resistance in the population."

Few new antibiotics have been developed in recent decades. Many researchers argue that this is because much of the low-hanging fruit — those antibiotics that are easy to discover and manufacture such as penicillin and erythromycin — have already been found. Anything coming down the drug pipeline next will be much less obvious to researchers or convenient to produce.

Some progress is being made on this front. A group of researchers at Northeastern University is developing techniques of growing certain types of bacteria in a lab that had never been grown before, bacteria which may turn out to be viable sources of new kinds of antibiotics.

But as Patel pointed out, pharmaceutical companies are in something of a bind when developing new antibiotics. While they are incredibly valuable for society, they are not especially lucrative, particularly because their use has to be limited to prevent antibiotic resistance from developing.

"It’s tough for a pharmaceutical company to say they’re going to invest in drug development, and then not be able to sell the product they’ve developed," Patel said.

Despite the many obstacles to effectively fighting this problem, there are many strategies that have potential to help stem the tide of resistance. And there appears to be an increasing sense of concern about this issue.

"There has been great leadership by the World Health Organization that developed a global action plan," Patel said. "And one of the things the global action plan calls for is for each country to develop their own action plans to address the problem of antibiotic resistance. And that is underway in all these different parts of the world."

In September, the United Nations plans to address the topic of antibiotic resistance at the General Assembly meeting.

Photo Credit: NIAID via Flickr