Feb 11th, 2019, 09:47 AM

Antibiotic Resistance, an End to Modern Medicine?

By Jackson Vann
Image Credit: The World Health Organization/Wikimedia Commons
Modern medicine's most important pillar, antibiotics, is becoming obsolete.

Over the past couple of years, antibiotic-resistant bacteria have made headlines around the world, and the 2019 World Health Organization's list of ten threats to global health has put antibiotic resistance on the list. Antibiotic resistance poses a real and pressing danger when it comes to global health.

Antibiotics are the foundations of modern medicine. Before their discovery in 1928 in the form of penicillin, getting an infection could be a death sentence if the immune system were to be compromised. Following the discovery of penicillin and others in the "golden age" of antibiotics, all bacteria that had been a threat since the dawn of humanity had finally been beaten, at least that is what we thought. Following the "golden age", bacteria began to evolve or mutate to neutralize antibiotics. This can be done through changing its membrane to keep antibiotics out; active efflux, in a sense pumping out antibiotics before it has a chance to damage the bacteria; neutralization, creating compounds that break down the antibiotics, etc. For every new antibiotic on the market, it is only a matter of time until a strain of bacteria mutates or evolves a way to resist it.

Image Credit: The Center For Disease Dynamic, Economics and Policy (CDDEP)

Increasingly, new antibiotics become obsolete almost as soon as they reach the market, only lasting one year on the market before some form of bacteria becomes resistant. A simple answer for antibiotic resistance is to just use another class of antibiotics, as they all work differently. This was the original school of thought, but it has led to the emergence of "superbugs", a strain of bacteria that has developed resistance to most conventional antibiotics. The only way to combat superbugs is the use of drugs of last resort (DoLR): often antibiotics that have been discontinued due to harmful side-effects such as Colistin due to the risks of damaging nerves, the kidneys, and the liver. But even now, superbugs have developed resistance against DoLR like Colistin, even though there are strict rules about their usage.

How did this happen and who is to blame? The short answer is everyone. Doctors have been readily prescribing antibiotics for anything, even in cases of viral infections. If you have ever gotten antibiotics for a cold, that is inappropriate usage. Antibiotics should only be prescribed in severe cases, since the majority of the time, the immune system is strong enough to fight off the infection. Patients are also to blame, often demanding antibiotics for small infections or viral colds, using them as a form of placebo. Patients also often fail to finish their entire antibiotic course as it reduces the chance bacteria will gain resistance. New methods of farming have led farmers to continually give animals antibiotics to keep them healthy in crowded unsanitary conditions. This leads to antibiotic-resistant diseases in animals that then jump to humans. Colistin, a DoLR, was used in Chinese pig farms and has led to Colistin-resistant bacteria. This has made the important DoLR unusable as resistance has spread worldwide. Hospitals have been struggling to control antibiotic-resistant bacteria outbreaks in entire wards, using pure ethanol, large UV spotlights that can be wheeled around, and extreme containment protocol. However, even with all these measures, patients are still getting infected with antibiotic-resistant bacteria.  Even new hospital wards that have opened and have been declared "MRSA Free" only retain their certification for a few months before MRSA has colonized part of the ward. This, in turn, exposes extremely vulnerable patients to aggressive and usually life-threatening infections. Poor hygiene and sanitation practices at home and in hospitals have also been attributed to the rise in antibiotic resistance.

Image Credit: Center for Disease Control and Prevention 

Antibiotic-resistant bacteria in average infects 2 million people annually in the U.S. and kills about 23,000, while in Europe, an estimated 33,000 die from antibiotic-resistant bacteria annually. Low-income countries often take the brunt of the effects, as medical infrastructure is not able to test and effectively treat these infections. Estimates place the number of babies in India who die due to antibiotic-resistant infections at over 58,000 annually, while in Thailand, antibiotic-resistant bacteria are attributed to over 38,000 deaths annually. This is not a small problem. Every year the numbers get progressively worse. This is a global threat that could take humanity back in time for disease treatment. And it's not just bacteria, there are reports of antifungal resistance, antimalarial resistance, and TB resistance, complicating treatment for very serious illnesses.

We are not hopeless in the fight. There are ways to deal with the treatment of antibiotic-resistant bacteria. Before anything is invested in new treatments, the first change that we need is a change in antibiotic usage: doctors should prescribe less medication, patients should be educated on how to properly take antibiotics, new laws should ban antibiotics in animal feed and antibiotic soap, and there should be an increase in testing capabilities to identify antibiotic-resistant bacteria. In terms of new solutions, there are two options: investing in new classes of antibiotics, a tried and true method, and the use of bacteriophages, a new experimental therapy that uses viruses to infect and replicate in bacteria, in turn, killing it without affecting the patient.

New classes of antibiotics used to hit the market often, but now there are only one or two in the development pipeline. This is due to the extreme expense of developing the next classes of antibiotics, something that the pharmaceutical industry doesn't want to pay for. This is exacerbated by policy-makers and the healthcare industry's plan to keep the next class of antibiotics on the shelves unless it is absolutely needed, meaning little usage and therefore little profit. There is no incentive to develop new antibiotics. Both Europe and the U.S. have looked at strategies to incentivize pharmaceutical companies. The U.S. has looked into creating a new rapid antibacterial approval pathway called Limited Population Antibacterial Drug (LPAD). Other strategies like research and development tax credits have also been proposed, which is estimated to result in a $1 billion increase in antibiotics and antifungal research over the next 10 years, equating to between five to six new classes of antibiotics/antifungals. However, the only piece of actual legislation that has passed into law provides for an additional five years of data exclusively for qualifying antibiotics/antifungals. Europe, on the other hand, has decided to work more closely with pharmaceutical companies to change the way that antibiotics are assessed. This will lead to smaller clinical trials, decreasing the overall cost of developing new classes of antibiotics. The EU has also invested $253.6 million in a public-private partnership to fund research on new classes of antibiotics with medium-sized enterprises and researchers. 

Then there are bacteriophages, the "new" solution to antibiotic resistance. Bacteriophages are viruses that target a specific group of bacteria to replicate in, inadvertently killing the bacteria in the process. They are very effective at this. Every day, bacteriophages kill between 15-40% of all bacteria in the ocean. Bacteriophages have been found to be effective against superbugs and antibiotic-resistant bacteria. This silver bullet of antibiotic resistance is not new. Research into bacteriophages took place around the same time as the discovery of penicillin. The majority of this research was conducted in the USSR, and bacteriophage therapy was used during World War Two by Soviet troops. Bacteriophage research was abandoned in the West due to the discovery of new classes of antibiotics and limited understandings of viruses. However, interest in phages has led to their revival, especially with advancements in our understanding of viruses. Bacteriophages have both upsides and downsides. They can be effective in cases of last resort; only targeting the specific bacteria, leaving healthy bacteria in the system; auto-dosing, increasing the number of phages as they infect and kill bacteria; low toxicity, humans are unlikely to trigger an immune response against the phages unlike like some forms of antibiotics; and easy discovery of new phages. However, many are questioning whether investing in this newer therapy is worth it, as antibiotics are already tried and tested. Other downsides include lengthy and difficult production, uncertainty in dosing, and lengthy response time compared to that of antibiotics.

For more information about bacteriophages check out this great video:

Antibiotic resistance is a serious issue that is affecting the global healthcare system. We have tools at our disposal that can fix this, but these tools must be used correctly. Through legislation, public-private partnerships, funding of new research, and global cooperation, this threat can be managed. In a world that is ever so interconnected, superbugs and resistance can easily spread from one corner of the world to the other. But even individuals can help better the situation. Be conscious about antibiotic usage, complete the antibiotic series, buy antibiotic-free meat, advocate for better legislation, and take part in better hygiene practices.