Efforts to fight antibiotic resistance aren’t “nearly radical enough” today, according to a new study.

Image credits Emilian Danaila.

Relying too much on reducing antibiotic use and implementing new drugs could lead to “disaster”, says Dr. Ben Raymond, of the University of Exeter. In a new study, Dr. Raymond proposes five rules for the “sustainable use” of antibiotics which would help us maintain the efficiency of this class of drugs and prevent antibiotic resistance from becoming a deadly problem.

Resistance fighters

“People think the best way to tackle antibiotic resistance is to give out fewer antibiotics and find new drugs. Those are important steps, but this approach alone is not nearly radical enough,” says Dr. Raymond, of the Centre for Ecology and Conversation on the University of Exeter’s Penryn Campus in Cornwall.

“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.”

What he proposes instead is a multi-pronged approach intended to prevent what the World Health Organisation calls “a post-antibiotic era in which common infections and minor injuries can once again kill.” The measures include taking steps to protect new drugs before resistance becomes a problem, diversifying the range of antimicrobials currently in use to avoid relying too much on a handful of drugs (which also speeds up the evolution of resistance for those drugs), and using data to design management plans for particular superbugs.

“This ‘business as usual’ approach can be disastrous, as exemplified by the history of resistance in gonorrhoea and the emergence of untreatable infections,” Dr. Raymond explains. “Resistance to new antibiotics can become widespread in two or three years, so new drugs must be partnered with more sustainable patterns of use.”

The five ‘rules’ outlined in the study are:

1. Prevention. Echoing the old adage, Dr. Raymond wisely notes that “resistance is easier to deal with before it becomes severe.” Avoiding heavy use of single drugs for extended periods of time creates less evolutionary pressure for its active compound (i.e. bugs have less need and opportunities opportunity to develop resistance to a particular compound, as they don’t see it that frequently).
2. Don’t rely on “fitness costs.” Some approaches call for break periods in the use of a particular drug, in the hope that bacteria resistant to it will die off to their competition because they carry resistance genes that are no longer useful (i.e. genetic dead weight.) While the idea behind the approach can work, resistance to a drug does not necessarily vanish because of an interruption in the use of a drug.
3. Limit bacteria’s ability to mutate drug-resistance genes. One approach is to use antibiotic cocktails, as microbes rarely develop resistance to multiple antibiotics at once. Slowly building a massive reservoir of antibiotic-resistance genes in the wild is “madness” according to Dr. Raymond. Traces of antibiotics in wastewater, or the use of antibiotics in livestock farming, are doing exactly that. “As an individual you are very unlikely to have acquired an antibiotic resistant microbe from an animal, but it’s highly likely that environmental contamination has helped some of the microbes in your body acquire resistance,” he says.
4. Low doses don’t work, but short courses might. A greater pool of mutations can give microbes the chance to resist low doses of antibiotics, so lowering the dose doesn’t prevent resistance from evolving. However a shorter, more intense course of treatment might benefit patients without giving the bugs a chance to evolve, he says.
5. Know your enemy. “If you don’t know what kind of resistance is around among patients or in your hospital, you could give people the wrong drug at the wrong time,” he says. “The more data you have, the better you can design your resistance management programmes. Resistance management programmes should target specific microbes or groups of microbes, rather than resistance in general.”

“Some humility in the face of natural selection can ensure that human creativity keeps pace with evolutionary innovation,” he adds, noting that other disciplines have a broader knowledge of resistance management, but that their input is “not widely appreciated” among microbiologists.

The paper “Five rules for resistance management in the antibiotic apocalypse, a road map for integrated microbial management” has been published in the journal Evolutionary Applications.