Welcome to the Post-Antibiotic Era

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Penicillin was isolated and discovered largely by accident in 1928. But the nascent study of penicillin and, more broadly, antibiotics would only come to a fore in 1945, when a septic patient consigned to leaving the mortal coil was given a second chance at life. The rise of antibiotics has been revolutionary and is one of the most significants medical advancements of the last century.

While Fleming’s discovery was not entirely intentional, his subsequent warning was certainly premeditated. In 1945 he was quoted as saying:

“The microbes are educated to resist penicillin and a host of penicillin-resistant organisms is bred out… I hope such an evil can be averted”.

What Fleming is referring to is anti-microbial resistance (AMR)- when pathogenic microbes become immune to the very medicine used to treat them. Some examples of this are MRSA, Streptococcus Pneumoniae and strains of salmonella.

Fleming’s warnings would be in vain, because antimicrobial resistance is no longer a sobering prediction of the future, nor a rare and exceptional observation. These infections have in fact taken the lives of millions of thousands worldwide, with 700,000 dying every year. Moreover, there have been findings that all age groups are affected and around 70% of the deaths are healthcare related. That is to say, the effects of these infections predominantly occur in healthcare settings.

That’s not to say that AMR can’t get worse. By 2050 we may see up to 10,000,000 lives taken by superbug infections. Assistant Director-General of WHO, Dr Keiji Fukuda, predicted that:

Without urgent, coordinated action by many stakeholders, the world is headed for a post-antibiotic era, in which common infections and minor injuries which have been treatable for decades can once again kill. Unless we take significant actions to improve efforts to prevent infections and also change how we produce, prescribe and use antibiotics, the world will lose more and more of these global public health goods and the implications will be devastating.

Of course, it’s important to note that AMR isn’t a new phenomenon, predating the usage of antibiotics themselves. Any microbe can become resistant, and resistance may be intrinsic or acquired. And bacteria have had millions of years to deal with naturally-occurring antibiotics.

What are the causes?

When an antibiotic fails to kill every single microbe in an infection, those that remain will divide and pass on their resistance to progeny. This is how selective pressure leads to resistance. However, when even the non-resistant bacteria divide, a mutation may change the genome and bestow their offspring with resistance. And through a process known as horizontal gene transfer, resistant bacteria can pass on this trait to microbes other than their offspring.

All of that is inevitable. From the introduction of antibiotics the bacteria have been developing resistance exactly as described. What’s making it even worse is our own misuse of antimicrobials. At one end of the spectrum there’s self-medication. In low-to-middle income countries where a professional’s treatment is too expensive, a person might look to other sources for advice. These sources might be family, friends or a shady video on the Internet telling them to take antibiotics unnecessarily.

At the other end of the spectrum there are problems within entire industries, such as agriculture. Overuse of antibiotics in farming means resistant bacteria may divide rapidly in animals, ready to be passed on to humans consuming the meat. Even healthcare professionals misuse them, with studies in France finding that 30-60% of antibiotics prescribed are unnecessary.

As with many things recently, the COVID-19 pandemic will have a major impact on AMR. Hospitals are already a breeding ground for these infections because the patients have compromised immune systems. In many cases when they receive the antibiotics some microbes will survive and thrive. Poor infection control make them likely to spread the resistant bacteria to others. With COVID-19 huge numbers of patients are being admitted and more than 90% are receiving antibacterial treatment. Some of the effects can be observed already, as in Wuhan over half the deaths are because of secondary infections, many from multidrug-resistant bacteria.

What can we do?

AMR bacteria are only a problem because they resist the effects of all known antibiotics. So why not just invent some more antibiotics?

In reality it’s easier said than done. According to WHO there are 252 drugs in preclinical testing (being tested on animals) and of those up to 5 may become in the coming decade. Most antibiotics were invented prior to the 1970s and pharmaceutical companies have little financial incentive to develop drugs that are to be used infrequently. And if that wasn’t an issue the drugs can have serious side-effects, such as deafness in those treated for multi-drug-resistant tuberculosis.

One solution is preventing the development and spread of resistance. Doctors will identify which cases require antibiotics and will prescribe the shortest course possible. Hospitals will strive to increase infection control. But it goes without saying that this can only go so far, that patients will still need antibiotics and disease will continue to spread.

What does that leave us? Doctors may have to resort to entirely new treatments. One of the most promising is phage therapy. This uses bacteriophages- small viruses- to infect the AMR bacteria. They can then force the bacteria to clone the viruses until the strain causes them to undergo lysis. This has proven to be safe in the limited testing in Georgia, but it’s effectiveness at a large scale is unknown. The phages have to be adapted to target only the AMR bacteria, which is a difficult and time-taking procedure.

Ultimately there are no solutions likely to replace antibiotics altogether, as of yet. If we remain complacent, AMR could have financial and social impacts orders of magnitude greater than COVID-19. While there is hope with the effectiveness of some treatments, it is becoming clear that we are approaching a crucial point in the fight against AMR. The ball is in our court.


References

  1. Antimicrobial resistance, https://www.who.int/en/news-room/fact-sheets/detail/antimicrobial-resistance, February 15, 2018
  2. Antibiotic Resistant bacteria responsible for over 30000 Deaths in Europe, https://www.pharmaceutical-journal.com/20205705.article?firstPass=false, November 7, 2018
  3. First Global Report on Antibiotic Resistance, https://www.who.int/mediacentre/news/releases/2014/amr-report/en/, April 30, 2014
  4. About Antibiotic Resistance , https://www.cdc.gov/drugresistance/about.html, March 13, 2020
  5. Amy W. Scientists Develop self cleaning, bacteria repelling plastic wrap, [online], https://edition.cnn.com/2019/12/13/health/superbug-repelling-surface-intl-scli-scn/index.html, December 13, 2019
  6. Theo M , The Perfect Predator?,https://www.telegraph.co.uk/global-health/science-and-disease/perfect-predator-inside-tbilisi-clinic-pioneering-radical-superbug/ , December 17, 2019

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