Is Antimicrobial Resistance Evolution Accelerating?

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A team of researchers from Freie Universität Berlin and ETH Zurich studied if antifungal and antibiotic resistance emerge faster than in the past

No 199/2020 from Oct 23, 2020

Scientists from Freie Universität Berlin and Eidgenössische Technische Hochschule Zürich (ETH Zurich) investigated how long it takes for resistance to emerge after the introduction of a new antifungal or antibiotic. Jens Rolff, evolutionary biologist at Freie Universität Berlin and one of the authors of the study, considers the results to be potentially alarming. The findings suggest that drugs that have been introduced more recently lose their potency faster than older drugs in most cases. The evolutionary dynamics leading to this development urgently warrant in-depth study to inform public health measures and drug development. Statistics already show that several 10,000 people in the EU alone die from antibiotic resistant infections annually. The results of the study were published in the journal PLOS Pathogens.

The first antibiotics were employed 80 years ago - a medical revolution. Such drugs, however, lose their efficacy to kill, as microbes evolve resistance against them. Such phenomena have been studied extensively. The team from Freie Universität and ETH Zurich studied whether the time between introduction of antimicrobials and subsequent resistance emergence of antimicrobials is becoming shorter for newer drugs. They analyzed data from widely known studies and reviews. The researchers found that, indeed, resistance evolution is accelerating. Drugs that have been introduced later in the antibiotic era are met with faster microbial resistance evolution. But they also noted that the data sources are difficult to identify, and hence the conclusions for antibiotics are unreliable. In comparison, they also studied fungicides. Here the result was the same: resistance evolution in fungal pathogens was faster against newer fungicides. In contrast to the antibiotic data, the original data sources could be identified.

"It is therefore essential to understand the evolutionary processes leading to resistance against antibiotics and fungicides," Christopher Witzany, one of the authors, stressed. A common explanation for resistance evolution is the increased usage of antimicrobials. This seems to be an unlikely explanation in the case of newer antibiotics though. They are often held back as reserve antibiotics for difficult to treat infections, therefore the quantities produced and used are relatively low.

Another possible explanation for the faster resistance emergence is the increased surveillance and research activity resulting in faster detection, as the scientists discuss in the article. This would be a "best-case scenario." The evolutionary past could be another explanation, as many antibiotics and fungicides are based on older antimicrobials or derived from natural substances. If resistance against previous antimicrobials prevails in pathogen populations, resistance evolution against new but related antimicrobials is much easier, suggests Jens Rolff. Moreover, other environmental stressors, such as heavy metals, have been shown to select for antibiotic resistance.


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