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A major threat to public health all over the world today is the rise of harmful “superbug” bacteria that are very difficult to kill with antibiotics. One of the most well-known superbugs is methicillin-resistant Staphylococcus aureus (MRSA), an especially difficult-to-treat variety of the disease-causing bacteria staph. Although antibiotic-resistant bacteria like MRSA may not receive much media press or popular attention, the illnesses and deaths related to superbugs surpasses those of more well-known diseases like Ebola or AIDS. The current problem with antibiotic-resistant bacteria comes partially from the natural evolution of bacteria, as well as from improper use and overuse of antibiotics by humans. As a result, in the “arms race” between germs and medicines, bacteria are learning to outsmart us much faster than we can invent new treatments. However, even though bacteria are outpacing us, and antibiotic resistance continues to be an urgent problem, there is hope that humans will be able to take back the lead through more thoughtful and responsible use of antibiotics.

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 infect us and get us sick. When disease-causing bacteria strike, we look to doctors to provide antibiotic medications and feel assured that modern medicine 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 bacterial antibiotic resistance is a current and “major threat,” that could affect “anyone, of any age, in any country” [1]. These concerns have been echoed by many other leading health agencies worldwide, including the US Center for Disease Control (CDC) [2]. In other words, the rise of antibiotic-resistant “superbugs” is a very real and pressing issue at the forefront of public health today.

To understand this problem, let’s start by taking a closer look at the story of one particular superbug, known as 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 that can be responsible for problems ranging from pimples, to blood infections, to pneumonia [3]. The “M” in MRSA refers to the antibiotic methicillin. Thus, MRSA is a special type of staph that is hard to treat with methicillin and other antibiotics [3].

Methicillin was first used effectively against staph in 1959 [4]. However, as early as 1960, there were reports of staph that could not be killed by methicillin, and throughout the ‘60s, hospitals in Europe, Australia, and the United States reported more and more outbreaks of methicillin-resistant Staph [4]. Since the ‘60s, MRSA has become resistant not just to methicillin but to numerous other antibiotics. Now, despite the fact that there are well over a hundred types of modern antibiotics, only perhaps a dozen are still useful against MRSA [5].

But why should we even worry about MRSA? There are plenty of other diseases, after all, many of which are more famous and probably sound scarier.

CDC reports in 2005 and 2012 show that combined MRSA deaths and illnesses can surpass those of diseases that receive more popular attention, such as HIV/AIDS [14] and Ebola [13] (for detailed information, see Figure 1). Though MRSA can affect anyone, most of these cases occurred in hospitals and other healthcare settings and affected vulnerable individuals like infants, the elderly, and others with weakened immune systems [14].

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 [13] and CDC [14].

It’s worth noting that besides MRSA, there are many other antibiotic-resistant superbugs that cause additional cases and deaths every year. Thus, though superbugs may not receive much buzz, going by the numbers, it’s reasonable to be as worried about antibiotic resistance as we are about many other diseases.

Nature, evolution, and the survival of the most antibiotic-resistant bugs

MRSA first 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 natural process of evolution [7]. In a simple sense, evolution happens because, in any population of living things—whether it’s animals, plants, or bacteria—there are some individuals that are more favorably suited to their environment and therefore more likely to survive and pass on their qualities to future generations. Over time, these favorable qualities become more and more common.

For bacteria like staph, favorable qualities include resistance to antibiotics. Though bacteria possessing this quality may start out only as a small fraction of the bacterial population, over time, more susceptible bacteria are killed off by antibiotics, leaving only the bacteria that are the hardest to kill to reproduce and take over the population (Figure 2). Eventually, this leads to a whole bunch of superbugs like MRSA.

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 seem to take a long time, so how did Staph start becoming 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, meaning that in a single day, bacteria can go through dozens of generations. However, although nature is part of the reason for antibiotic resistance, there is another side to the story: humans.

Ever since we developed antibiotics, we have used them to treat a wide variety of diseases. But, every time we use an antibiotic, we give bacteria a chance to get ahead. Think about it like combat: every time we use a weapon, that is a chance for the enemy to observe the weapon and decide how best to counter-act it next time [15]. 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 out-smarting us is called an “arms race.”

The problems with antibiotic use are compounded when we use them for the wrong situations (for more detail, refer to [15]). Problematic behaviors include not taking the full dose of the antibiotics, saving leftover antibiotics for re-use, and sharing antibiotics with friends and family. Because antibiotic prescriptions must be matched precisely to the exact illness, casual usage often involves an incorrect dosage and/or inappropriate types of antibiotics, making the medications ineffective. Another misuse is when antibiotics are used for the wrong disease. Antibiotics are meant to treat bacteria, but there are many non-bacterial illnesses like the common cold, to flu, to chicken pox, against which antibiotics are useless.

Such antibiotic misuse is even more serious because there are always Staph and other bacteria lurking in our bodies and surroundings. When we use antibiotics in the ways described, not only are we treating ourselves ineffectively, we are also giving lurking bacteria another “peek” at our weapons and opportunity to out-maneuver 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–the bacteria in our microbiomes. Although you are probably aware of “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,” [8]. There are many benefits of the microbiome, including prevention of nasal Staph infections [9]. In a healthy person, the microbiome occupies all the space in the nose, leaving Staph no room to take up residence [9]. (For detailed discussion of the microbiome, refer to 10].

Thus, when we take antibiotics, we may not just be targeting the bad guys. Antibiotic medications can also wipe out the friendly bacteria that help make us healthy and prevent bacteria like MRSA from taking root. The risk of “friendly fire” on good bacteria exists for everyone, though young children are especially vulnerable [8,10], since their immune systems and microbiomes are still not fully developed.

The road ahead

Between 2005 and 2012, the CDC reported a decline in the number of MRSA illnesses and deaths, an improvement largely attributed to improved infection control [11]. This represents a significant step forward and demonstrates that we have made, and can continue to make, strides against MRSA and other antibiotic resistant bacteria. To this end, the CDC provides suggestions to patients on how to combat antibiotic resistance: take antibiotics only when doctors specifically say that they are necessary; follow prescriptions exactly, without skipping doses or stopping early; do not share antibiotics or save them for later [for full list of suggestions, refer to 12].

Antibiotic resistance is a real health challenge in the modern world. The urgency of today’s situation is due not just to natural bacterial evolution, but has also been accelerated by our own missteps in the way we use antibiotics. As we look to the road ahead, more responsible and careful use of antibiotics may be one of the factors that give us back the advantage in our race against the tiny, tenacious bacteria than endanger our health.

Vivian Chou is a Ph.D. student in the Biological and Biomedical Sciences Program at Harvard Medical School.

References

[1] WHO 2014 report, “First global report on antibiotic resistance: reveals serious, worldwide threat to public health.” http://www.who.int/mediacentre/news/releases/2014/amr-report/en/

[2] CDC 2013 report, “Antibiotic resistance threats in the United States.” http://www.cdc.gov/drugresistance/threat-report-2013/index.html

[3] Minnesota Department of Health on S. aureus facts and basics.  http://www.health.state.mn.us/divs/idepc/diseases/staph/index.html

[4] University of Chicago Medicine’s “MRSA history timeline 1959-2012” http://mrsa-research-center.bsd.uchicago.edu/timeline.html

[5] Infectious Disease Society of America’s 2011 article. “Guidelines on how to treat MRSA infections”  http://www.aafp.org/afp/2011/0815/p455.html

[6] WebMD 2007 article. “More US deaths from MRSA than AIDS.” http://www.webmd.com/skin-problems-and-treatments/news/20071016/more-us-deaths-from-mrsa-than-aids

[7] Howstuffworks basic explanation of “How Evolution Works.” http://science.howstuffworks.com/life/evolution/evolution1.htm

[8] Wired Magazine’s 2011 article, “Antibiotics: killing beneficial bacteria…for good?” http://www.wired.com/2011/08/killing-beneficial-bacteria/

[9] Public Library of Science (PLoS) One 2010 article. “The Human Nasal Microbiota and Staphylococcus aureus carriage.”  http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0010598

[10] Science in the News Signal to Noise 2013 article “Harnessing our Body’s Microorganisms to Combat Disease” http://sitn.hms.harvard.edu/flash/2013/issue137a/

[11] WebMD 2013 article. “Serious MRSA Infections in US Declining: CDC.” http://www.webmd.com/skin-problems-and-treatments/news/20130916/serious-mrsa-infections-in-us-declining-cdc?page=1

[12] CDC’s 2014 report, “Mission critical: preventing antibiotic resistance” http://www.cdc.gov/features/antibioticresistance/

For further information

[13] The United Nations World Health Organization http://www.who.int/en/

[14] The United States Center for Disease Control http://www.cdc.gov/

[15] A simple, thorough explanation of antibiotic resistance and its impacts by Tufts University.  http://www.tufts.edu/med/apua/about_issue/about_antibioticres.shtml

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