Unstoppable killers
The rise of antibiotic resistant bacteria: “superbugs”
For most of human history, bacterial infections often led to devastating illness and death. A minor ear infection could spread to the brain and kill you. A splinter could lead to amputation — or again, kill you. Basically, life was like that retro computer game Oregon Trail. Mostly, you died. Today, your doctor gives you a prescription for a “Z-pack,” and you’re good to go. But that could be coming to an end.
The antibiotic era is relatively recent. Clinical use of antibiotics began in the 1940s, about a decade after Alexander Fleming discovered penicillin [1]. Hailed as a miracle drug, penicillin became widely used. But shortly after, penicillin-resistance followed. Or did it come first?
Origins of Antibiotic Resistance
You might think: how can antibiotic resistance come before the drug is used? This concept is certainly confusing. According to the Centers for Disease Control & Prevention (CDC):
“The use of antibiotics is the single most important factor leading to antibiotic resistance around the world. Simply using antibiotics creates resistance.”- CDC [2]
But on the same CDC information page, you find the timeline image shown here. This timeline highlights that penicillin-resistant Staphylococcus were identified 3 years before the use of penicillin. This apparent discrepancy is actually a nifty lesson in evolution, and shows that you are more likely to find things when you look for them. The simple explanation comes down to frequency.
Bacteria divide rapidly, and they are constantly evolving — changing/adding/removing genes — through multiple methods. These constant changes occur completely independent of antibiotics. This means that, technically, antibiotic resistance can and does occur in the absence of any drug. Even if Alexander Fleming had never discovered penicillin, a few Staphylococcus bacteria would still mutate to become penicillin resistant. But they would be uncommon.
These rare resistant mutants become dominant through selection. The environmental change that drives selection is called selective pressure. The widespread use of antibiotics is a selective pressure that kills bacteria that are susceptible, leaving only the resistant strains to thrive.
So, we could modify the above statement by the CDC to make it more accurate: “Simply using antibiotics increases the frequency of resistance.”
The Bacterial Arms Race
You could imagine the CDC timeline as a race. Science is working at a desperate pace to develop new antibiotics, and bacteria are rapidly evolving to thwart these new therapies. Unfortunately, the odds are not in our favor. New antibiotics are being developed at a declining rate. You also may have noticed that some of the people in charge of the US government are not proposing increased funding for research. At the same time, the bacteria are not pausing in evolving resistance while we decide on budget priorities. Multidrug resistant strains of bacteria are becoming more prevalent, and recently a woman died in Nevada of a nearly completely antibiotic-resistant infection.
It is clear that we need to redouble our efforts to discover new antibiotics, and accelerate these desperately needed drugs through the approval pipeline.
Another approach is to synthetically modify existing antibiotics to thwart resistance. This is one of our oldest tricks. Methicillin is derived from penicillin and was designed to beat penicillin-resistant bacteria. But have you heard of Methicillin-resistant Staphylococcus aureus, or MRSA? It was found just 2 years after methicillin entered the clinic. Scientists continue to use this approach, and just recently, an exciting new study described modifications to vancomycin that give it multiple ways to kill bacteria, enabling it to overcome current vancomycin-resistant strains. The concept of attacking bacteria through a combination of pathways, either via a single drug or a multidrug cocktail, seems like a great idea. As an HIV researcher, I appreciate the therapeutic usefulness of combination antiretroviral therapy, as HIV can quickly evolve to defeat single drugs. So, why shouldn’t we attack antibiotic resistance in bacteria in a similar way?
Hopefully this modified vancomycin successfully squashes the emergence of resistant strains. But if history has anything to say about it… let’s just say I wouldn’t bet my life on it.
One strategy to stem the increase in resistance is antibiotic stewardship. This strategy is simply a focus toward limiting the use of antibiotics to only when they are clinically necessary. Often antibiotics are overprescribed or misused, so decreasing these practices would decrease selective pressure towards resistance. But even with optimal antibiotic stewardship, the bacteria will keep evolving, and eventually, resistant strains will become widespread. Stewardship simply buys us more time.
I recommend that we fight evolution with evolution.
A new (old) approach: weapons for a post-antibiotic future
Does it sound like I’m full of “doom and gloom” pessimism? Well, I’m actually optimistic that we can beat antibiotic resistance. We just need to change the game by including potentially radical shifts in strategies. I recommend that we fight evolution with evolution.
How do we harness evolution to protect us from antibiotic-resistant bacteria? One way is based on bacterial interference, or that bacteria compete with each other to live in an area or “niche”. If you have good, healthy bacteria living in/on you, they fight off bad invaders. This is similar to the use of probiotics, although science can take it much further than just eating yogurt.
Bacterial warfare was actually described much earlier than therapeutic antibiotics. Louis Pasteur described his 1877 studies: “…life impairs life…colonization with one microbe makes it difficult for another microbe to grow.” So, since the nineteenth century, scientists have known that microbes compete against each other to live. In fact, the chemical warfare microbes engage in is where we get most of our antibiotics. Bacterial interference takes advantage of this competition between microbes.
A clinical application of bacterial interference was already shown to be effective. In the 1960s, a deadly Staph called “80/81” infected newborn infants in hospital nurseries. Doctors noticed that babies who carried a different strain of Staph were protected from 80/81 and didn’t get sick. They then isolated one of these protective strains and called it “502a.” They found that intentionally colonizing newborns with 502a directly after delivery, in the nose and umbilical cord, could safely and effectively prevent infection with the deadly Staph 80/81.
A recent study of newborns in India found that intentional colonization of infants with a protective strain of Lactobacillus plantarum protected them from sepsis. In this placebo-controlled clinical trial, more than 75% of infants were protected from subsequent infection. This was achieved without antibiotics. The newborns were simply given a dose of the protective bacterium and fructooligosaccharide (a “prebiotic” sugar that supports bacterial colonization). This amazing study found that the benefits were not limited to sepsis. The newborns also had decreased risk for respiratory infections, and more!
These alternative approaches show us that antibiotics aren’t our only defense against deadly bacteria. They illustrate the potential of using protective bacteria to fight pathogens. Importantly, protective bacteria can also adapt: harnessing the power of evolution to defend us from evolving enemies.
For more, follow me on Twitter @sciencethomas
Other articles by Thomas Packard:
•Think HIV is Cured? Not Yet
•The Flu Shot Can’t Give You the Flu
•Fighting the Plague — A Story of HIV/AIDS
•The Flu Shot Can’t Give You the Flu
•Can Cold Weather Give You a Cold?
•Shrinking funding for scientific research shrinks the economy
Note: This and other things I write are my opinions about science and medicine, they should not be considered medical advice. If you have personal questions or concerns, talk with your doctor about these topics.
