Five rules for antibiotics: Calling for a new paradigm in resistance management

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The invention of penicillin, the first true antibiotic, in 1928 was a monumental day in the history of medicine. Over 90 years later, antibiotics are a common feature in all our lives. We get a bacterial infection, go to the doctor, get an antibiotic, and it clears up. Easy.

However, today there is increasing concern over the resistance of bacteria to antibiotics, which has the power to curtail use of these drugs in treatment of serious diseases. Diseases like gonorrhoea, necrotizing fasciitis, and staph infections already have antibiotic-resistant varieties, and resistance only continues to increase among various bacterial species.

Antibiotic resistance is an evolutionary process. It is caused by small, random mutations in individual bacterial cells. These lucky mutants aren’t killed by the antibiotic treatment, and later multiply to form new strains of antibiotic-resistant bacteria known as “superbugs.”

There is no question of when antibiotic resistance will become a major global issue; it already has. The World Health Organisation says antibiotic resistance is rising to dangerous levels worldwide and warns of “a post-antibiotic era in which common infections and minor injuries can once again kill.”

A new study from the University of Exeter proposes five rules for more “sustainable use” of antibiotics. These include guidelines on when and how to use antibiotics, as well as advice for gathering data to design resistance management programmes. Dr Ben Raymond, of the Centre for Ecology and Conversation on the University of Exeter’s Penryn Campus in Cornwall, led the study and says that continuing to rely so heavily on antibiotic use and discovering new drugs could be catastrophic in the long term.

“Even if we can keep finding new drugs, disaster will follow if we use them in the same way as we use current ones. No drug yet discovered is evolution proof, and the typical practice of using single drugs at once, in unprotected ‘monotherapies’ is unsustainable,” he says.

The study’s five rules are:

  1. Prevention. “Resistance is easier to deal with before it becomes severe,” Dr Raymond said. Avoiding heavy use of single drugs for extended periods of time reduces the evolutionary pressure on bacteria to resist that drug.
  2. Complete all courses of treatment. Some plans depend on stopping use of a drug in the hope that resistant bacteria will die out when their mutations are no longer beneficial to their survival. This can work, but Dr Raymond warns that resistance to a drug does not necessarily go away just because use of that drug stops.
  3. Limit supply of mutations. Because antibiotic resistance comes about by random mutations, it’s unlikely that individual bacteria will develop resistance to multiple antibiotics. Using combinations of antibiotics can ensure fewer individuals survive to evolve into superbugs. This rule also includes working to limit antibiotic contamination of wastewater and use of antibiotics in animals, as this can increase the supply of resistance genes in the environment.
  4. Shorter, more intensive courses of antibiotics. This method of treatment gives bacteria fewer opportunities to evolve into superbugs, because a much greater pool of mutations can give microbes resistance to lower doses of antibiotics.
  5. Information is power. Researchers need to be gathering more targeted data for individual microbes, rather than resistance in general. Dr Raymond says, “The more data you have, the better you can design your resistance management programmes.”

These rules provide a starting place for managing resistance in the modern day, but Dr Raymond also adds that broader lessons of resistance management are not always well appreciated by microbiologists, and that evolutionary biologists and clinicians need to join the conversation if resistance is to be managed effectively and sustainably.

In the face of bacterial resistance, this study suggests that scientists from across fields need to come together for the benefit of humanity. The study calls for a broader shift in paradigm surrounding antibiotic usage, one in which sustainability in the long term is valued in equal measure with short-term clinical outcomes.

Dr Raymond added: “Some humility in the face of natural selection can ensure that human creativity keeps pace with evolutionary innovation.” If humans fail to find sustainable solutions to these issues, we could be facing a new dark age in medicine, and sooner than we think.

This post was written by Miles Martin and edited by Ella Mercer.

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