Live Fast, Die Young: The War On Antibiotic Resistance
Antibiotics have provided a short-term advantage in the arms race against bacteria, but can we stay ahead? Zaria Gorvett discusses.
AsianScientist (Mar. 15, 2013) - Birth. For 200,000 years of human history, the moment of delivery marked the beginning of a struggle; a life-long war with infectious disease. Birth was lurid with death. With every scratch, cough, and embrace, humans ran the gauntlet of infection.
Elective surgery? Out of the question. Appendicitis? Fatal. Sexually transmitted diseases? Incurable.
The cornerstones of modern medicine - surgery, chemotherapy, life-support, and neo-natal care - are underpinned by the drugs that revolutionized healthcare. Life as we know it depends on antibiotics, but there's a problem. Since the availability of the first antibiotic in 1932, bacteria have been slowly developing resistance. Now, in what has been described as an "antibiotic apocalypse," effective antibiotics are running out.
How have bacteria developed antibiotic resistance so rapidly?
The use of antibiotics reveals a surprising reality. Farmers in China, the United States, and Europe have been dosing animals with the precious drugs for decades. In China, the world's largest producer of antibiotics, veterinary use of antibiotics is four times higher than in the United States. In fact, nearly half of the 210,000 tons of antibiotics produced in China annually are fed to animals. While in humans antibiotics save lives, they are fed to animals to improve their health in crowded feedlots and encourage their growth.
A recent collaboration by the Chinese Academy of Sciences and Michigan State University has revealed the magnitude of the problem. The researchers investigated the prevalence of resistant bacteria in soil and pig manure at farms that routinely fed their pigs antibiotics. The team found 149 genes for antibiotic resistance, an assortment which would collectively provide resistance to all classes of antibiotics currently in existence. Some genes were present at 28,000 times the levels in soil samples not taken from farms.
Despite the usefulness of antibiotics, they are no universal panacea. According to Chinese medical experts, antibiotics are responsible for the deaths of 80,000 people in China every year. The average Chinese citizen consumes 138 g of antibiotics per year- ten times the average U.S. consumption. This startling statistic is the result of the compulsive prescription of antibiotics for inappropriate illnesses, but China is not alone. In India, where antibiotics were available over the counter until last year, pharmacy sales of one class of antibiotics - the carbapenems - increased by nearly six times between 2005 and 2010. The epidemic of over-use has been attributed to a culture of expectation by the public, financial reward for doctors, and poor regulation, and is contributing to the tide of antibiotic resistance that threatens to destabilize public health worldwide.
Instead of prudently reserving the drugs that have saved millions of lives, they are being lavished on our meat, and taken by the people who simply don't need them. Of course, there are more than enough antibiotics for everyone. To understand the problem with the use of antibiotics in agriculture and over-prescription, we must first understand bacteria.
Our bodies are a soup of over 10,000 species of bacteria. Some are good, and some are bad, and they are constantly multiplying, mutating, and shuffling genes. The way that genes that confer antibiotic resistance spread can be likened to the way that a beneficial tool spreads among warring tribesmen. Say if, for example, a single warrior were presented with the instructions for making a shield. He goes back to his tribe, and shows his friends, some of who ask for the instructions too. In the next raid, they survive under the protection of their shields, and so over time, with shield-owners surviving the most attacks, and sharing the technology with their neighbors, eventually the whole community is comprised of shield-owning warriors.
"The enemy of my enemy is my friend" - Chinese proverb
Our bodies may be home to billions of bacteria, but space is at a premium. Penetrating the layers of established bacteria is tricky; a useful natural defense against nasty intruders. However, antibiotics are a great leveler. In addition to introducing a selective pressure in favor of resistant bacteria, antibiotics also wipe out the beneficial species.
What will life be like without antibiotics?
In the pre-antibiotic era, most people could expect to live to just 35. On average, most people would have lost at least one child to disease. Many would have been left disabled by infections in childhood. The threat of early death that has haunted humanity from prehistoric times may have been forgotten, but without antibiotics, a reversion is inevitable.
“The gaunt and grisly form of death” - Charles Dickens on tuberculosis, 1839
Tuberculosis has threatened life in India for over 3,500 years. In 19th century Europe, before the development of antibiotics, tuberculosis was responsible for the deaths of one in seven people. The disease has claimed the lives of Tutankhamen, Karl Marx, and George Orwell. Now, tuberculosis is running rampant, with 34 percent of all new cases occurring in Southeast Asia and 1,000 deaths in India per day in 2008, according to the World Health Organization. Drug resistance is also proving increasingly problematic, with 440,000 new cases of multi-drug resistant tuberculosis (DR-TB) emerging every year. While most DR-TB bacteria are susceptible to last resort antibiotics, many patients cannot afford medication, and those who can endure side effects that include deafness, nausea, and psychosis.
There is only one antibiotic currently recommended for the treatment of shigella infections. As a result of widespread resistance, the infection - which causes potentially fatal bloody diarrhea - is becoming increasingly difficult to treat, especially in children.
Antibiotic resistant gonorrhea has pushed doctors to the use of "last line" antibiotics, but resistance to even these is increasing, news that predicts an imminent global epidemic.
Collectively, tuberculosis, shigella, and gonorrhea are three of the five most common infectious diseases in China.
Not only is antibiotic resistance hampering the control of infectious diseases, but it may have a profound effect on modern medicine. The insidious rise of antibiotic resistant bacteria over the last decade threatens to undermine progress in healthcare over the last 80 years. Hospital acquired infections are making many surgical procedures, cancer treatments and life support tools increasingly risky. A high proportion of hospital acquired infections are now caused by methicillin resistant Staphylococcus aureus (MRSA), a highly resistant bacterial species that affects people at their most vulnerable.
How do resistance genes protect bacteria from antibiotics?
Bacteria have three main tactics for evading destruction by antibiotics, and the instructions for each strategy are encoded in their genes. Some bacteria choose disguise; they change their chemical uniforms to prevent recognition by antibiotics, which would bind and destroy them. Others swear by assault; actively seeking out the antibiotic to destroy it before it enters their cells. Finally, the most dangerous of all, the 'gram-negative' bacteria pursue eradication; simply removing antibiotic molecules from their cells by pumping them out.
Once resistant bacteria have proliferated in animals, they exit in manure. They may leach into the water supply or hitchhike into people's homes on butchered meat.
We are drifting towards a dystopian future, a reversion to a pre-antibiotic era, in which routine operations are deadly, and childhood killers currently reduced to distant memories re-emerge.
In the war against infectious disease, new weapons are badly needed, but conserving the ones we already have may prove even more important. The alarming truth is that no new classes of antibiotics have been discovered since 1987, yet we are squandering our remaining resources on livestock and those that don't need them. Antibiotics provided a short-term advantage in the arms race against bacteria, but to stay ahead a global effort is needed. The question is: are we a worthy opponent?
Copyright: Asian Scientist Magazine; Photo: Gino Carteciano/Flickr/CC.
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