It's not an overstatement to say that most of modern medicine and our health hinges on the effectiveness of antibiotics. Whenever you go to the hospital for an operation — a hip replacement, an ACL repair, heart surgery — almost without exception, doctors will give you a dose of antibiotics to prevent infection. Antibiotics also make the cesarean section, one of the single-most life-saving procedures on the planet, possible.

But there's a scary side to antibiotics, too. More and more, bacteria have outsmarted the exact medicines meant to kill them. Some of these bacteria-fighting wonder drugs either no longer work or are expected to stop working very soon. Just consider the latest superbug outbreak at a Southern California hospital: the New York Times reported that, already, seven patients have been infected, including two who died, and almost 200 others have been exposed.

These nightmare scenarios will become more common for one, simple reason: we're not addressing this problem of "antibiotic resistance" quickly enough. As a new report warned, if actions aren't taken soon, drug-resistant infections — like the one in California — will kill an extra 10 million people per year around the world by 2050, and associated cumulative costs between now and then will soar to over $100 trillion.

To respond to what is increasingly seen as an urgent problem, governments have been implementing policies and awards that encourage faster drug development and discourage the overuse of antibiotics. Unfortunately, these actions don't seem to be stemming the tide of a scary situation.

When our antibiotics don't work

Antibiotic resistance is a natural phenomenon. Given that bacteria multiply by the billions, it makes sense that a few will randomly develop a mutation in their DNA that provides some protection from our pharmaceuticals. So the more we use antibiotics, the more we allow these mutated drug-resistant bacteria to multiply and thrive. If we use them too much — such as when they’re not needed for viral infections, like nearly all sore throats — eventually superbugs will come to dominate the bacterial world.

In a world without antibiotics, the threshold of risk from infection in any procedure suddenly rises dramatically. For some patients, the risk would be too great to bear. Procedures that are absolutely necessary would become more dangerous.

It’s almost unimaginable how going back to a pre-antibiotic era would affect health care "It’s almost unimaginable," said Professor Kevin Outterson, of Boston University School of Law, "how going back to a pre-antibiotic era would affect US health care." As Jirka Taylor, an analyst at Rand Corporation, put it, "If you had a 5 percent chance of contracting an infection that had a 40 percent case fatality rate, would you still be interested in submitting to a relatively mundane procedure such as hip replacement, when your survival did not depend on it?"

And yet, we continue to overuse, misuse, and abuse antibiotics to the point where we're speeding up the natural process of resistance — slowly rendering them useless. We already have multi-drug-resistant gonorrhea and strains of tuberculosis that fend off all antibiotics.

The situation has become so dire that people are imagining our return to the pre-antibiotic era. In one piece, science writer Maryn McKenna describes a world before antibiotics and what we'll face again when the ones we have fail: "Before antibiotics, five women died out of every 1,000 who gave birth. One out of nine people who got a skin infection died, even from something as simple as a scrape or an insect bite. Three out of ten people who contracted pneumonia died from it. Ear infections caused deafness; sore throats were followed by heart failure."

Three steps to tackling antibiotic resistance

There are many things that need to happen to address this growing global threat. These can be neatly summarized into three imperatives: conservation of existing antibiotics; innovation for new antibiotics; and access to antibiotics for everyone who needs them.

Step 1: Conservation

First, we need to do whatever it takes to make sure our current stocks of antibiotics remain effective for as long as possible. This is probably the most important — and most challenging — area of action since there are so many entrenched practices that need to change and we can’t just throw money at this issue.



But the good news is that science has revealed a few strategies for conserving antibiotics.



One is to remove financial incentives and marketing by antibiotic manufacturers that lead to irrational use. Right now, manufacturers earn profit based on how many antibiotics they sell — which of course leads them to do whatever they can to promote the sale and use of these drugs, even if that quickens antibiotic resistance.

Another is to phase out antibiotics used by livestock farmers for animal growth promotion and routine prevention. This is important because, right now, 80 percent of antibiotics in the US are consumed by animals — not humans. It would be one thing if these drugs were used to treat sick animals, but they’re actually mostly used as a substitute for healthy living conditions and for their side effect of causing animals to grow faster. Efforts by the US government to restrict antibiotic use in animals have been pushed back by the powerful livestock lobby at every turn.

Doctors and hospitals can also improve the way they prescribe and use antibiotics. Basic infection-control practices in hospitals and health-care settings need to be reinforced to ensure drug-resistant bacteria are not proliferating in the same place where the people most vulnerable to them are based.

Doctors also need better medical education about appropriate antibiotic prescribing, and the public needs to stop demanding an antibiotic prescription from their doctors whenever they’re sick. This probably means that all of us need to remember one thing: that antibiotics have no effect on viruses, the cause of flu, colds, and nine out of ten sore throats. As Sarah Kliff pointed out recently, while researchers have long know that antibiotics can't treat bronchitis, a staggering 71 percent of bronchitis cases continue to be treated with antibiotics.

Step 2: Innovation

Second, we need to scale-up innovation for new antibiotics to replace those that now don't work. Given we’ll want to severely restrict how we use future antibiotics and given their effectiveness may not last for very long, companies have not exactly been eager to invest in R&D in this area. Because of this, the last twenty years have been described by many as a "discovery void" in antibiotics development. So right now, we have very little in the pipeline.

Realistically, new antibiotics development will likely depend on massively increasing public funding for research and development in this area. This includes R&D funding for new antibiotics, diagnostics to make sure that we can better target our use of antibiotics, vaccines so we can avoid the need for antibiotics, and alternatives to these drugs altogether.

Step 3: Access

Third, and finally, we need to ensure universal access to antibiotics for timely and appropriate treatment. Delays allow bacteria to spread, and a lack of access allows them to persist in bacterial reservoirs.



The inconsistent availability and use of diagnostics that can test which antibiotic may be best for each infection means too many patients are prescribed an antibiotic to which the bacteria causing their infection is resistant. The availability and routine use of rapid diagnostics for methicillin-resistant Staphylococcus aureus (MRSA), for example, has been linked to lower levels of this deadly bacteria that currently kills 9,670 people each year in the US alone. Vaccination uptake must also be improved — especially in places that have recently spurned these true modern-day miracles — to reduce reliance on antibiotics in the first place. Bacterial vaccines include those for diphtheria, tetanus, pertussis, cholera, and typhoid. Insufficient use of diagnostics and vaccines harms our health and furthers resistance.

What needs to happen next to fight antibiotic resistance



Ultimately, these actions need to be tackled simultaneously. Access without conservation and innovation will speed resistance, which is counterproductive. Conservation by itself constrains access and undermines innovation by decreasing the size of the market for antibiotics. Innovation without access is unjust, and without conservation, simply wasteful.

Drug-resistant microbes spread between countries as easily as we hop on An airplane

Action also needs to be taken globally. Drug-resistant microbes can spread between countries as easily as we can each hop on an airplane. Scientists have already been using genetic analysis to track the international migration of antibiotic resistance, finding it moves to and from the US, as well as to and from rich and poor countries alike.



Acting globally also helps minimize the cost of action, such as by ensuring that restrictions on antibiotic use in animals affect all livestock farmers equally around the world — thereby preserving current competitive market dynamics — and not just those from early-adopting countries.

How to actually achieve the needed level of simultaneous global action remains a mystery. But this is a conversation that researchers and politicians are now having. Several researchers have even called for an international treaty on the matter. As an editorial in the most recent issue of the Bulletin of the World Health Organization argues: "there is a clear role for a binding international legal framework to encompass the issues of access, conservation and innovation. When paired with strong implementation mechanisms, international law represents the strongest possible way in which countries can commit themselves to act."

Whatever the antidote to drug resistance, it’s not only clear that leadership from countries like the US will be vital, but also that all of us — from CEOs to senators, doctors' associations, and individual patients — have an important role to play.



Welcome to Burden of Proof, a regular column in which Julia Belluz (a journalist) and Steven Hoffman (an academic) join forces to tackle the most pressing health issues of our time — especially bugs, drugs, and pseudoscience thugs — and uncover the best science behind them. Have suggestions or comments? Email Belluz and Hoffman or Tweet us @juliaoftoronto and @shoffmania. You can see previous columns here.

