The Arms Race Between Germs and Medicine Vivian Chou Medicine, Science, Science & Medicine They may be the tiniest living organisms on our planet, but despite their small size, harmful bacteria – often known as “bugs” or “germs” – can pack quite a punch when they get us sick. When disease-causing bacteria strike, doctors provide antibiotic medications that will restore our health in no time. Unfortunately, in the “arms race” between bacteria and antibiotics, human medicine is beginning to lose ground, and bacteria are beginning to fight back. The World Health Organization (WHO) underscores the severity of the situation, stating in April 2014 that antibiotic resistance is a current and “major threat,” that could affect “anyone, of any age, in any country.” These concerns have been echoed by many other leading health agencies worldwide, including the US Center for Disease Control (CDC). There is no doubt that the rise and presence of antibiotic-resistant “superbugs” is a pressing issue at the forefront of public health today. To understand why these superbugs are so problematic, let’s consider the story of methicillin-resistant S. aureus (MRSA). What’s MRSA and why should I care about it? The “SA” in MRSA stands for Staphylococcus aureus (staph), a very common bacterium causes a range of problems: pimples, blood infections, or even pneumonia. The “M” in MRSA refers to the antibiotic methicillin. Thus, taking all the parts of the acronym together, MRSA is a special type of staph that is hard to treat with methicillin and other antibiotics. Methicillin was first used effectively against staph in 1959. However, there were reports of staph as early as 1960 that could not be killed by methicillin. The MRSA Research Center at the University of Chicago reports that throughout the 60s, hospitals in Europe, Australia, and the United States reported more and more outbreaks of methicillin-resistant Staph. Since the 60s, MRSA has become resistant not just to methicillin but to numerous other antibiotics. Today, we have over a hundred types of antibiotics, but only around a dozen are still useful against MRSA. Given that there are plenty of other diseases to worry about, why, in particular, should we be concerned about MRSA? CDC reports in 2005 and 2012 show that combined MRSA deaths and illnesses surpass those of diseases that receive more popular attention such as HIV/AIDS and Ebola (for detailed information, see Figure 1). Though MRSA can affect anyone, most cases occur in hospitals and other healthcare settings: those with weakened immune systems like infants and the elderly tend to be the most susceptible. Figure 1 Comparison of MRSA cases and deaths to other infectious diseases. Bars represent total number of cases with light shades indicating non-fatal illnesses and dark shades indicating fatalities. Numbers of people affected and killed by MRSA can exceed, sometimes by several fold, the numbers of those affected and killed by well-publicized diseases. With the exception of the MRSA 2005 statistics included for comparison purposes, all data is the most recent from the WHO and CDC. It’s worth noting that in addition to MRSA, there are many other antibiotic-resistant superbugs that cause additional cases and deaths every year. Going by the numbers, it’s reasonable to be just as worried about antibiotic resistance as we are about many other diseases. Nature, evolution, and the survival of the most antibiotic-resistant bugs MRSA arose when we began to use antibiotics to combat infections. But why would our medicines, which were effective at the beginning, lose their potency later on? The answer, in part, lies in the process of evolution. Evolution occurs in any population of living things – whether it be animals, plants, or bacteria – because there are some individuals that are better suited to their environment. Those who have more favorable qualities (i.e. traits), survive and pass their good genes onto future generations. Over time, the qualities that are most favorable are the ones that persist. For bacteria like staph, favorable qualities include resistance to antibiotics. The population of bacteria with this quality may, at first, be small. Bacteria that are not resistant are killed by antibiotics, but the bacteria that are more difficult to kill survive, reproduce, and eventually take over the population, giving rise to superbugs like MRSA (Figure 2) Figure 2 Evolution of resistance to antibiotics by bacteria. (A) An individual is infected by disease-causing bacteria, such as Staph (represented by dots). The population of bacteria that causes this infection is mixed and consists of bacteria ranging from those vulnerable to antibiotics (green) to those that are much harder to kill (darkest red). (B) The infected individual takes an antibiotic medication. This antibiotic kills most of the bacteria, but not the most resistant ones. (C) The resistant bacteria multiply. Now, the population no longer consists of a mix of vulnerable and resistant bacteria, and tends to contain mostly resistant bacteria. (D) The new population of resistant bacteria can go on to infect other individuals. (E) This new infection of resistant “superbugs” is very difficult to eliminate with antibiotics. The antibiotics arms race: How we are letting the germs get ahead Evolution might sound like something that takes a long time, so how did Staph become resistant to methicillin within a year and to dozens of other antibiotics in just a few decades? One reason is that bacteria reproduce very quickly – sometimes in under an hour. That means bacteria can go through dozens of generations in a single day. While nature accounts for part of the reason for antibiotic resistance, there is another side to the story: humans. The discovery of antibiotics has been revolutionary, and they’ve been used to treat a variety of diseases. But every time we use an antibiotic, bacteria are given a chance to get ahead. Think about it like combat: every time we use a weapon, we give the enemy the chance to observe the weapon and decide how best to counteract it. Unfortunately, bacteria are much better and faster at evolving than we are at finding and inventing new antibiotics. It’s no accident that our struggle to keep developing new antibiotics as bacteria become better at outsmarting us is dubbed an “arms race.” As the Alliance for the Prudent Use of Antibiotics at Tufts University outlines, the problems associated with antibiotic use are compounded when we use them for the wrong reasons. Not taking the full dose of the antibiotics, saving leftover antibiotics for re-use, and sharing antibiotics with friends and family can all lead to complications. Since antibiotic prescriptions are matched precisely to the exact illness, casual usage (i.e. incorrect dosage and/or inappropriate types of antibiotics) renders the medications ineffective. Another example of misuse is when antibiotics are used for viruses: antibiotics are meant to treat bacteria, but there are many non-bacterial illnesses like the common cold, flu, and chicken pox, that cannot be cleared with antibiotics. Antibiotic misuse is even more serious because there are more than just Staph bacteria lurking in our bodies and surroundings. When antibiotics are abused in the ways described above, bacteria get another “peek” at our weapons and have a window of opportunity to outmaneuver us. Thus, seemingly minor behaviors can add up to the evolution of superbugs like MRSA, among others. Antibiotics can hurt the good guys, too Besides giving harmful bacteria a head start, using antibiotics also runs the risk of damaging our allies. While there are “bad” bacteria like the Staph that make you sick, there are also many “good” bacteria that live on and in our bodies, called the “microbiome.” Researchers with the Pace Lab at the University of Colorado also noted that having a healthy nasal microbiome, for example, can help prevent nasal Staph infections: all the other bacteria in the nose prevent Staph from taking up further room. In other words, when we take antibiotics, we may not just be targeting the bad guys. Antibiotics can also wipe out the friendly bacteria that keep us healthy and prevent bacteria like MRSA from taking root. The risk of “friendly fire” on good bacteria exists for everyone, but young children are especially vulnerable since their immune systems and microbiomes are still not fully developed. The road ahead Between 2005 and 2011, the CDC reported a decline in the number of MRSA illnesses and deaths, an improvement largely attributed to improved infection control. This finding represents a significant step forward and demonstrates that we have made – and can continue to make – strides against MRSA and other superbugs. To this end, the CDC provided suggestions on how to combat antibiotic resistance: take antibiotics only under doctors’ orders; follow prescriptions (without skipping doses or stopping early); and do not share antibiotics or save them for later. Antibiotic resistance is a real health challenge in the modern world, the urgency of which has been accelerated by the severe misuse of antibiotics. Moving forward, more responsible and careful use of antibiotics may help give us the dominant hand in our race against the tiny, tenacious bacteria than endanger our health. Further Reading WHO Global Report on Antibiotic Resistance. Maryn McKenna. “Antibiotic resistance: The last resort” Nature. July 2013. “The antibiotic alarm” March 2013. University of Chicago MRSA History Timeline 1959-2012. Leslie Pray. “Antibiotic Resistance, Mutation Rates and MRSA” Nature Education. Maryn McKenna “Antibiotics: Killing Off Beneficial Bacteria … for Good?” August 2011. Ilana Kelsey “Harnessing our Body’s Microorganisms to Combat Human Disease” Harvard Signal to Noise. March 2013. Tufts University Fact Sheets on antibiotic resistance, possible actions against the problem, and proper antibiotic use. Heidi Ledford. “Promising antibiotic discovered in microbial ‘dark matter’” January 2015. Image credit: Methicillin-Resistant Staphylococcus aureus (MRSA) Bacteria via Flickr