Analysis of two decades of antibiotic resistance shows that antibiotic use is not the only driver of the emergence of superbugs

For the first time, researchers have analyzed the impact of antibiotic use on the increase in treatment-resistant bacteria over the past 20 years in the United Kingdom and Norway. They show that while the increase in drug use has amplified the spread of superbugs, it is not the only factor.

Researchers from the Wellcome Sanger Institute, University of Oslo, University of Cambridge and collaborators conducted a high-resolution genetic comparison of the bacteria. They compared more than 700 new blood samples with nearly 5,000 previously sequenced bacterial samples to answer questions about the factors that influence the spread of antibiotic-resistant Escherichia coli (E. coli).

The study, published in The Lancet microbe, shows that increased use of antibiotics in some cases leads to an increase in the number of bacteria resistant to treatment. However, researchers confirmed that this varies depending on the type of broad-spectrum antibiotic used. They also discovered that the success of antibiotic resistance genes depends on the genetic makeup of the bacteria that carry them.

Recognizing all of the major factors that cause antibiotic resistance can help better understand how these bacteria spread and what stops them. This could then better inform public health interventions that use a comprehensive view of the environment to help stop the spread of treatment-resistant infections.

The E. coli bacteria is a common cause of blood infections worldwide. The type of. The coli that causes these infections is usually found in the intestine, where it does no harm. However, if it enters the bloodstream due to a weakened immune system, it can cause serious or even fatal infections.

Posing an additional challenge for healthcare providers, antibiotic resistance, particularly multidrug resistance (MDR), has become a frequent feature of these infections. In the UK, more than 40% of E. coli bloodstream infections are resistant to a key antibiotic used to treat serious infections in hospital.

Rates of antibiotic resistance in E. coli vary globally. For example, the rate of resistance to a different antibiotic, commonly used to treat urinary tract infections caused by E. coli, varied between 8.4% and 92.9% depending on the country.

Antibiotic resistance has been a topic of research for decades, and surveillance data from previous studies have consistently shown an association between antibiotic use and increased frequency of MDR in bacteria worldwide, including included in the United Kingdom.

Previous studies have suggested stable coexistence of E. coli strains. resistant and non-resistant coli bacteria and, in some cases, non-resistant bacteria do better. However, previously it was not possible to assess the role of genetic factors due to the lack of unbiased large-scale longitudinal data sets.

This new study, led by the Wellcome Sanger Institute, University of Oslo and collaborators, is the first time it has been possible to directly compare the success of different strains of E. coli. coli between two countries (Norway and the United Kingdom) and explain differences based on levels of antibiotic use nationally.

Analyzing data spanning nearly 20 years, they found that antibiotic use was linked to increased resistance in some cases, depending on the type of antibiotic. One class of antibiotics, non-penicillin beta-lactam antibiotics, was used on average three to five times more per person in the UK than in Norway. This has led to a higher incidence of infections with a certain strain of E. multidrug-resistant coli.

However, the UK also uses the antibiotic trimethoprim more often, but the analysis did not reveal higher levels of resistance in the UK when comparing common strains of E. coli. coli found in both countries.

The study found that the survival of MDR bacteria depended on the strains of E. coli present in the environment. Due to this and other selective pressures in a region, the researchers concluded that it is not possible to assume that widespread use of one type of antibiotic will have the same effect on antibiotic-resistant bacteria widespread in different countries.

The scientists emphasize that their results warrant continued research efforts to identify other factors that lead to the spread of E. coli and other clinically important bacteria in various ecological contexts. Further research is needed to fully understand the combined effect of antibiotics, travel, food production systems and other factors that determine levels of drug resistance in a country.

Better understanding the strains that can outcompete antibiotic-resistant E. coli can lead to new ways to help stop the spread. For example, attempts to increase the amount of non-resistant, non-harmful bacteria in an area.

Dr Anna Pöntinen, co-first author from the University of Oslo, Norway and a visiting scientist at the Wellcome Sanger Institute, said: “Our large-scale study has allowed us to begin to answer some of the long-standing questions on the causal causes. multi-resistant bacteria in a population. This research was only possible thanks to the national systematic surveillance of bacterial pathogens that took place in the United Kingdom and Norway. Without such systems in place, scientists would be significantly more limited in terms of what can be learned using the power of genomics.

Co-author Professor Julian Parkhill from the University of Cambridge added: “Our study suggests that antibiotics are modulating factors in the success of antibiotic-resistant E. coli, rather than being the only one. cause. -spectrum of antibiotics and shows that their influence varies according to countries and regions. Overall, our comprehensive genetic analysis shows that it is not always possible to predict the impact of antibiotic use on a region without knowing the genetic makeup of bacterial strains in that environment.”

Professor Jukka Corander, lead author from the Wellcome Sanger Institute and the University of Oslo, Norway, noted: “Treatment-resistant E. coli is a major global public health problem. Although it has long been accepted that the overuse of antibiotics plays a role in the increase and spread of superbugs, our study highlights that the level of drug resistance in widespread strains of E. coli can vary considerably.

“The use of antibiotics will constitute a selective pressure, and our study shows that this is not the only factor influencing the success of these bacteria. It is crucial to continue to use genomics to gain a detailed understanding of the factors underlying bacterial success if we are to control the spread of superbugs.