Health

You're Becoming More Immune to Antibiotics

This week, President Obama announced the first White House plan to confront the growing specter of antibiotic resistance, a $1.2 billion dollar effort that would involve both the Department of Health and Human Services and the Department of Agriculture. The proposed measures would encourage the development of new antibiotics, while discouraging medical and agricultural misuse. While experts at the CDC are happy that this oft-overlooked public health issue is receiving attention, critics of the plan feel its vague language betrays an inability or unwillingness to meaningfully regulate Big Agriculture. While measures in the plan would create a coordinated system for monitoring outbreaks, as well as funding better screening technologies for detection of infections, these efforts focus on misuse on the individual level; if commercial use of antibiotics in livestock is allowed to continue unchecked, reduction of patient non-compliance and practitioner over-prescription may be irrelevant.

So why should our government’s lackluster efforts on this front concern us? What do we risk as more strains of bacteria become resistant to treatment? And what behaviors, by what actors, are accelerating the process of resistance?

During the last century, medicine has seen remarkable advancements. Chemotherapy and radiation, organ transplants, intensive care, hip replacements, and a vast array of other surgeries and treatments are all important staples of modern care. Impressive and diverse though these technologies seem, nearly all of them rest upon a single, vulnerable foundation: the continued efficacy of antibiotics. Antibiotics, the drugs we rely on to resolve bacterial infections, are a fundamental component of many of the procedures we associate with modern medicine. Without them, invasive treatments, surgeries, and immunosuppressant medications – all of which carry high risk of infection – would become too dangerous to administer. Without them, simple cuts and scrapes would once again be life-threatening. Without them, maternal mortality would skyrocket, hospitals would become dangerous hubs of infection, and the structure of global agriculture – along with food security around the world- would be threatened.

This makes the rise of drug-resistant superbugs all the more alarming. This dire picture of the future is hardly far-fetched; the continued misuse and overuse of antibiotics is creating drug-resistant superbugs at an alarming clip. Couple this with the pharmaceutical industry’s dwindling interest in antibiotic research, and the scale of global emergency we may face can hardly be overstated.  Unless significant changes are made to prevent antibiotic resistance on both the individual and structural level, what we call modern medicine will collapse like a house of cards.

The origin of antibiotics

A mere 87 years have passed since Alexander Fleming made one of the greatest accidental discoveries in human history. In September 1928, after a month away on a family vacation, he returned to the lab where he had been studying the Staphylococcus aureus bacteria. The specimen had become contaminated with a mold, and where the mold grew, the bacteria had died. Recognizing the implications of a potent bacteria-killer, he turned his attention to the study and development of his discovery, eventually called “penicillin” (a much more appealing choice than its original name, “mold juice”). Fleming and penicillin launched an era of antibiotic research and set the stage for myriad invasive medical procedures. Surgeries and treatment courses which suppress the immune system, as chemotherapy does, carry high risk of infection, and would not have been viable without the advent of antibiotics. In 1945, Fleming received the Nobel Prize in Medicine. While wrapping up his acceptance speech, he sternly warned of his contribution’s fragility if misused, saying, “there is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug make them resistant.” Even then, the issue of antibiotic resistance plagued the minds of the day’s top medical minds.

So what is antibiotic resistance? How does it occur, and why is it occurring?

Simply put, resistant bacteria are able to withstand antibiotics that treated them effectively in the past. Like other living organisms, bacteria adapt and evolve. The more we use antibiotics, the more we risk the creation of strains of bacteria resistant to that particular drug. Particularly, exposure to antibiotics in an uncontrolled or poorly controlled dosage or environment helps create bacteria that are no longer vulnerable to the drug. Despite efforts to regulate antibiotic use, this exposure happens in a variety of ways.

Patient misuse

First, we have patient non-compliance and practitioner error. When patients fail to complete a course of antibiotics, they may not destroy their infection entirely. TB, for example, requires 180 days of consistent antibiotic dosage to be cured, and patients begin to feel recovered much sooner. Thus, multi-drug resistant TB (MDR TB)- resistant to two or more of the primary drugs used to treat TB- emerged as a threat to containment of the disease . In 2011, the WHO reported 310,000 cases of MDR TB worldwide. In 2012, that number leapt to 450,000 cases. But MDR TB is still responsive to second-line drugs that an even more potent strain is not. Extensively drug resistant TB (XDR TB) was first documented in 2006. Although people associate international public health efforts with the distribution of medication and resources, the dissemination of information is an equally important component. In recent years, huge public awareness projects have stressed the importance of completing 180 full days of treatments across afflicted areas. Additionally, the treatment plan known as DOTS- an acronym for Directly Observed Treatment, Short-course- requires patients to return to a clinic daily and be observed taking the medication- has rapidly become a staple of TB care. The WHO refers to DOTS as “the heart” of its Stop TB Initiative.

Over-prescription

Patients aren’t the sole culprit of antibiotic misuse, however. Physicians also over-prescribe or mis-prescribe antibiotics fairly commonly. Antibiotics only treat bacterial infection; they are not effective against viruses. However, people who are sick with a cold or flu may mistakenly believe that antibiotics are called for and pressure their doctor for a prescription. The CDC estimates that up to 50% of antibiotics prescribed in U.S. hospitals are unnecessary.

Education is the first line of defense against over-prescription and misuse, but the U.S. healthcare system has become so fractured, overloaded and bureaucratic, it’s difficult to coordinate dissemination of public health information. Where half a century ago, people talked about visiting their doctor, today patients are unlikely to develop a personal relationship with a single doctor. Medicare patients see an average of two different primary care physicians and five specialists working across four separate practices in a given year. And our one-on-one time with doctors has been shortened significantly as well.

In the 1970s, huge increases in the cost of medical care saw the introduction of “managed care,” the system we use now, where insurance companies serve as middlemen between doctors and patients. Because medical care is provided on a fee-for-service basis, doctors are incentivized to see as many patients as possible, as quickly as possible. Quantity, rather than quality, becomes the measure of a doctor’s efficacy, a system which is as dissatisfying to the physicians as it us to patients. All of this serves to erode communication and trust. In such a limited time frame, care is provided with minimal explanation. Although doctors are careful to remind patients to complete their course of antibiotics, they rarely delve further into the issue; they simply don’t have time to explain drug resistance in bacteria ten times a day.

Environmental contamination

Even if individual behaviors are significantly modified and human error reduced, we still have to look to institutional misuse of antibiotics and environmental contamination. Two major industries, agriculture and pharmaceuticals, are contributing to the emergence of drug-resistant bacteria. Their regulation is vital to addressing the looming threat of a post-antibiotic world. Unfortunately, that regulation is easier proposed than instituted, and efforts to curtail rampant abuse of antibiotics have been met with political pushback for decades.

On the agricultural end, we have mass consumption of antibiotics by farm animals. In fact, an estimated 80% of the antibiotics consumed in the U.S. annually are fed to the animals we, in turn, eat. The factory-like structure of modern industrialized farming means much of our meat is raised in overcrowded, unhygienic environments, where the distribution of antibiotics to curtail infection is necessary. Additionally, cows, pigs, and chickens are fed a steady low dosage of antibiotics simply to encourage weight gain. In fact, a 2001 study by the Union of Concerned Scientists found that upwards of 70% of the antibiotics consumed nationally that year were distributed to well animals.

At a 2010 Hearing for the House Subcommittee on Health, Antibiotic Resistance and the Use of Antibiotics in Animal Agriculture, the FDA testified that animals should only be given antibiotics under the supervision of a veterinarian, and sparingly. The CDC, USDA, WHO and American Medical Association all echoed concerns that antibiotics usage in food animals is exacerbating the microbial resistance crisis. Studies like this one conducted by the USGS in 2006 have found that runoff from animal feeding operations causes significant contamination of local streams and well water. For decades, drugs have laced the feed of these animals with only the barest restrictions; prescriptions for the mass use of antibiotics on farms was not required.

But criticism of these practices are hardly new; they have come under fire since the 1970s, when the FDA first confirmed the emergence of antibiotic-resistant bacteria in livestock, but regulatory action has been slow in coming. In 1977, the FDA announced it would ban certain antibiotic uses in agriculture; however, the House and Senate appropriations committees passed resolutions to stop the ban from taking effect. The FDA then failed to take further action until 2012, when several environmental and consumer advocacy groups, including the National Resources Defense Council, brought a case against the regulatory body. Judge Theodore Katz of the United States District Court for the Southern District of New York ruled that, by identifying the health risks of antibiotic use on factory farms 35 years earlier, then failing to implement new restrictions, the FDA was in violation of its own regulations.

Still, the new guidelines implemented after the court’s ruling are hardly stringent. The FDA is asking drug makers to voluntarily begin requiring prescriptions for many of the antibiotics used on factory farms. Because revoking approval for drug uses is a complex and drawn-out legal process, the FDA hopes to avoid years of appeals and limited progress by asking, rather than telling, companies to comply. In other words, the FDA wants to outright ban the use of the antibiotics, and would do so if the pharmaceutical companies distributing them weren’t equipped with powerful legal teams bent on slowing or halting regulation.

2012’s push was hardly the first or last attempt to curtail the use of antibiotics in agriculture. In 2007, a Senate bill introduced by Senator Ted Kennedy and a House bill introduced by Representative Louise Slaughter both died. In 2013, companion bills in the Senate and House were again defeated. The House Bill, the Preservation of Antibiotics for Medical Treatment Act (PAMTA) was sent to committee. The Senate Bill, Preventing Antibiotic Resistance Act (PARA), was introduced by Dianne Feinstein and received bipartisan sponsorship. It too failed.

Resistance from the Pharmaceutical Industry

The second large environmental offender- another that will require major structural change if we hope to make meaningful and lasting progress heading in the fight to slow resistance- is the pharmaceutical industry itself. The process of manufacturing antibiotics creates contaminated wastewater, and its release into the environment has also spurred the development of drug resistance. In the U.S., treated wastewater can be used for crop irrigation, and study after study conducted by our own regulatory agencies indicates that human pharmaceutical products are indeed ending up in our water supply this way.  In a 2009 Associated Press Survey of 62 major water providers in major metropolitan areas, 34 did not consent to testing; of the remaining 28, 24 reported the presence of pharmaceutical products.

Contaminated Water Supply

Unsurprisingly, contaminated runoff is much more common in regions were pollution standards are less stringent or less enforced. Transnational pharmaceutical companies have relocated their manufacturing operations from Western countries to India, Pakistan, Bangladesh and China for cost reasons. Factories across the region – home to some 2.9 billion people and more that 40% of the world’s population – have been found to discharge wastewater directly into local sewage infrastructure without treatment. A recent study by experts in Korea and Pakistan titled “Global risk of pharmaceutical contamination from highly populated developing countries” and published by Elsevier, an academic publishing company that publishes medical and scientific literature, explores this issue in depth and can be found here. As might be expected, the study finds that: The application of untreated wastewater (industrial and domestic) and biosolids (sewage sludge and manure) in agriculture causes the contamination of surface water, soil, groundwater, and the entire food web with pharmaceutical compounds (PCs), their metabolites and transformed products (TPs), and multidrug resistant microbes.

Stalled R&D

Coupled with the industry’s acceleration of resistant bacteria development through improper waste disposal comes their deceleration of R&D for new generations of antibiotics. As old drugs are phased out due to inefficacy, we have relied on the introduction of new, more powerful ones to treat the new, more powerful bacteria, in something of an accelerated evolutionary arms race. However, because strains of bacteria become resistant to individual drugs so quickly, the money in developing and patenting new antibiotics can’t rival the profit margins of, say, a drug used to create chronic disease. Why develop a new antibiotic if it won’t be marketable in a decade? Conversely, the efficacy of other types of drugs remains constant. A drug like Prozac or another anti-depressant,will need to be taken consistently for years on end. All of that translates to more profit – and profit is the bottom line. In 2011, Pfizer, one of the last major pharmaceutical companies still participating in the development of new antibiotics, shut down its antibiotic R&D, citing shareholder disinterest.

Big pharma develops drugs based on financial incentive rather than need, there is significant risk to public safety when those two often overlapping- but not perfectly corresponding- motives diverge. The “invisible hand” of the economy distributes wealth according to supply and demand, but it simply isn’t designed to account for the “demand” of the collective good. Everyone- even executives at pharmaceutical companies- wants to avoid a post-antibiotic future, but individually, no one is looking to “purchase” that future. Unlike an individual drug, which is a single, material good with a price point, the abstract good “avoiding antibiotic resistance” is the result of decisions which carry limited financial advantage. Such goods require too many inputs of a buy/sell, supply/demand, up/down economy. Money flows in the direction of short-term, individual need, and where that doesn’t correspond with – or where, indeed, it contradicts with, long-term, collective need, we run into trouble. The economy is changeable, but here, it is not intelligent; there’s no ghost in the machine, so to speak. 

Of course, the goal on a regulatory level is to then create artificial alignment between social need and economic reward. Thus, we arrive at the ironic place of subsidizing our drug companies to produce the new drugs we need- drugs that are needed in part because of their own negligence. New legislation introduced by Rep. Phil Gingrey of Georgia will do just that. This past December, the Antibiotic Development to Advance Patient Treatment Act (ADAPT) was introduced to Congress. Along with shortening and accelerating the approval process for new antibiotic drugs, which will cut costs for pharmaceutical R&D, the bill provides economic incentives for development of the new classes of drugs we desperately need to be producing. Importantly, the bill also puts new guidelines in place for the tracking of drug-resistant infections, and loosens restrictions on experimental usage for critically ill patients. It’s good that our government is attempting to address this pressing public health issue, and many of the stipulations of the bill will move us forward on drug development. However, this legislation, when viewed in conjunction with our representatives’ unwillingness to implement basic and widely called for restrictions on big agriculture and big pharma, demonstrates the hierarchy of values guiding our lawmakers’ actions. Consideration for the health of the American people, and indeed, the world, is secondary to the maintenance of corporate relationships, and direct action to improve public health must never impede the profitability of industry.

Like all public health crises, the causes and exacerbating factors of antibiotic resistance are varied and complex. Misinformed individuals are playing a role, but their actions are also eminently predictable results of a poorly structured environment. Without adequate medical care available, especially among the most vulnerable Americans, patients are unlikely to have a clear picture of their own health or public risks. Without consistent treatment by a single doctor, patients are less likely to trust the advice of their practitioners, or ask follow-up questions about their care. In a system that incentivizes speed and imposes patient quotas, doctors have less time to explain care thoroughly, and are likely to diagnose patients less accurately. When the government refuses- or is unable- to hold meat suppliers to safe standards, big agriculture will continue to ignore scientific consensus on their role in the coming post-antibiotic age. And when pharmaceutical companies must be bribed to produce the drugs we so desperately need, we create a cycle of taxpayer responsibility for corporate cost.

President Obama’s new plan represents a step in the right direction, in the sense that more money is being allocated to address a serious national and international public health crisis. But that step falls directly in line with past efforts, in that it disproportionately addresses the less crucial, less structural causes of antibiotic misuse, while downplaying obvious regulatory failings.

Alexander Fleming didn’t expect to return home from a family vacation to find the world’s most valuable mold juice waiting for him in his lab. He merely recognized the importance of what so fortuitously materialized. It was the very human combination of happy accident, informed consideration, and deliberate action that brought us the miracle of penicillin. Today we encounter the opposite sort of accident; a situation created by the dangerous intersection of ignorance and greed. If deliberate action in the face of accident built modern medicine, only deliberate action can save it now. We must look curiously upon what we have wrought; we must seek, like Fleming before us, to understand what is growing in our lab today. We must decide that we can use the things we know to build a better future for medicine. We must not let the foundation crumble; we must not let the house that Fleming built fall into ruin.