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The Post-Antibiotic Era: The Clone Wars

Bacteria S. Aureus VISA 2, Photo: CDC/Matthew J. Arduino,DRPH

Upon a physical exam and history taking, your doctor might diagnose you with a throat infection and prescribe antibiotics. In some cases, a throat culture will be taken: a sample from your throat is placed on a petri dish for the bacteria currently residing there to grow. This test will tell your healthcare provider exactly which strains of bacteria are causing your disease, information with which they can tailor the treatment for your specific illness.
And for many years, that was the end of it. After a short course of antibiotics (usually a week or two), you will be cured from the pathogens causing your disease. Not anymore.

Infections: A New Hope
Up until 1928, infections were a major cause of mortality: every infection was life threatening, and hospital wards were full of people in serious condition from a minor scratch. The biggest plagues, taking hundreds of millions of lives, such as the black death, were impossible to contain.
All of that changed when a Scottish researcher by the name of Alexander Fleming returned to his lab after a vacation on September 3rd, 1928. Going through his petri dishes, he noticed a peculiar thing – on one of the plates, dotted with bacterial colonies, there was a contamination of fungi. And around that fungi, no bacterial colonies were anywhere to be seen.
Fleming collected the liquids secreted by the fungi and applied them to the same bacteria, and lo and behold: the bacteria died!
This was the discovery of the first “antibiotic” – a substance capable of killing bacteria while leaving human cells unharmed; and also the mark of a new era, the antibiotics era, in which humanity armed itself in the fight against microbial pathogens.
He named the substance “penicillin”, after the fungus producing it, Penicillium.
Over the next half century, over 20 new families of antibiotics were discovered, either naturally occurring in bacteria or fungi like penicillin, or developed specifically to combat specific strains.
But bacteria weren’t slow to follow.

Discovery and development of new antibiotics, Photo: WHO

Resistance: The Germs Strike Back
Different families of antibiotics work by inhibiting the bacterium’s ability to grow. Some classes of antibiotics prevent bacteria from being able to build its cell wall (e.g penicillin), while others prevent bacteria from replicating its DNA (e.g ciprofloxacin), and many other types exist.
All antibiotics must be very specific in their actions: they must not affect the human or animal cells, while killing bacterial ones. And bacteria use this to their advantage.

Over millions of years, different strains of bacteria engage in a never ending evolutionary arms race. With limited resources, a bacterial strain capable of producing a toxin neutralising competing strains would have the upper hand. But the competing strains aren’t always left lagging – they develop resistance to the toxin.
This back and forth development struggle has been going on for long, but only recently humans pitched in. And things got complicated.

Spread: Attack of the Clones
Most evolutionary processes, such as the development of resistance to antibiotics, take generations upon generations of bacteria exposed to nonlethal concentrations of the antibiotic, allowing them to slowly develop mechanisms to cope with it, and for the resistant strain to spread.
In nature, only a minority of bacterial colonies of a specific strain ever come across a new antibiotic, and even if they survive to develop resistance, the chances of that strain spreading across the world are slim.

With our use of antibiotics, suddenly almost every bacteria causing disease in humans is exposed to antibiotics. Ear infection? Here’s some Amoxicillin. Sore throat? some cephalexin might help. And this rise in exposure, and mainly the overuse (and misuse) of antibiotics has been the main cause of the rise in resistance that we now see today.

Agar plates coated with bacteria showing no growth around antibiotic pills, while antibiotic resistant strains grow, Photo: Wikimedia Commons

We have been using antibiotics way too much than warranted:

• Prescribing antibiotics for the flu or common cold, which might present in a similar fashion to bacterial infections. The flu and the cold are caused by viruses that are completely unaffected by antibiotics.
• Giving antibiotics to all livestock. Growing cattle and chickens in mass amounts in limited places makes infections commonplace. Antibiotics are routinely given to all of the animals to prevent that, even when no infection is present.
• Prescribing antibiotics to many infections that would otherwise pass easily and without complications, and when the use of antibiotics does not help to shorten the course, or alleviate the symptoms, of the disease.
  Moreover, people often stop taking their prescribed antibiotics once they start feeling better, and don’t complete the full course of treatment.

These practices cause bacteria to be exposed to huge amounts of antibiotics in nonlethal dosages. This, in turn, allows them to slowly grow resistant to these antibiotics, generating new strains of bacteria resistant to all of our arsenal of weapons against them. And we are left defenseless.

Superbug Comic, Photo by: DES Daughter

MRSA: The Phantom of Menace
Over the years, more and more strains of multiple drug resistant (MDR) bacteria have emerged. Their spread and limited treatment abilities have made them a growing burden on patients and healthcare systems.
Pathogens such as Multiple Resistant Staphylococcus Aureus (MRSA), Multi-drug-resistant tuberculosis (MDR-TB), and more recently Extremely drug-resistant TB (XDR TB), have emerged.

This has led Thomas Frieden, the director of the American Centers for Disease Control and Prevention (CDC), one of the world’s leading authority on infectious disease, to say in 2014: “We talk about the pre-antibiotic era and the antibiotic era; if we’re not careful we will soon be in the post-antibiotic era.”
Since then, many programmes to surveil the spread and development of MDR strains have gathered plenty of much needed information about how these bacteria infect patients and spread around. But not much has been achieved in combating these pathogens.

Response: The Force Awakens?
Take a closer look at the timeline above of antibiotic discovery and development. Many new classes of drugs have been in use from the first one in 1928 until the late 1980’s. But nothing since. Termed the “discovery void”, no new classes of antibiotics have been developed in the past couple of decades. Many reasons account for that: lack of government funding; lack of awareness amongst researchers, healthcare providers and the public; and the lack of economical value for drug companies to invest the millions of dollars required for making new antibiotics all contribute to this.

This must change in order for us to be able to deal with the ever changing arena of combatting infectious diseases, and the governments of the world have been focused, albeit slow, in their response:
The US government has initiated a “National Action Plan for Combating Antibiotic-Resistant Bacteria”, that includes allocating funds specifically for the development of new antibiotics and therapeutics against emerging resistant strains.
The European Union has commissioned the ARNA project, Antimicrobial resistance and causes of non-prudent use of antibiotics in human medicine, aimed at better understanding the causes of antimicrobial resistance and how to combat them.
The World Health Organization (WHO) has several programmes meant to follow the development of resistant strains, contain them, and notify health bodies about emerging threats.

Will all this be enough? Only time will tell, but until then, you can help.

Take Home Message: Return of the Jedi
Don’t let the dark side win. There are things you can do yourself to help combat this situation:

• Don’t demand antibiotics from your healthcare provider for every little fever. Ask them whether antibiotics are warranted for your ailment.
• When prescribed antibiotics: Always take the full course. Even if you feel better after a couple of days.
• Don’t take antibiotics without a prescription from your doctor. Using leftover pills from previous prescriptions or ones from family members is dangerous.
• Be aware. Spread awareness. Knowledge is power, and utilising it is the best way to work towards a better future.

Further Reading: Episode VIII
World Health Organisation (WHO), Antimicrobial Resistance: Global Report on Surveillance, 2014
Julie Beck, June 27, 2015, Antibiotic Resistance Is Everyone’s Problem, The Atlantic
Centers for Disease Control and Prevention (CDC), Antibiotic / Antimicrobial Resistance

Yuval Novik is an undergraduate researcher in molecular biology and a lover of all things medicine, science and technology. He is also a full-time sceptic and occasional daydreamer.