Use of short -term antibiotics linked to long -lasting resistance in intestinal bacteria

Researchers at the University of Stanford report that the use of ciprofloxacin leads to persistent antibiotic resistance in human intestinal bacteria, resistance emerging independently through various species and lasting for more than 10 weeks.

Resistance to antimicrobials (AMR) is a global health problem linked to millions of deaths each year. It is largely motivated by excessive and inappropriate use of antibiotics. Previous efforts to study RAM have greatly supported in vitro experiences and animal models, which are not to reproduce all the complexity of human microbial environments.

In the study entitled “In short, the use of antibiotics leads to human intestinal bacteria towards low -cost resistance”, published in NatureThe researchers carried out a longitudinal metagenomic study to explain how the resistance evolves in vivo.

Sixty healthy adults received ciprofloxacin, 500 mg twice a day, for five days. Over a period of 20 weeks, the participants collected 16 stool samples, which gives 960 samples for analysis. The metagenomic sequencing of the hunting rifle was carried out on all samples, generating an average of 18.8 million readings per sample. A calculation tool called Polypanner has been developed to identify real polymorphic sites over time.

The researchers rebuilt 5,665 genomes representing commensal bacterial populations and identified 2.3 million genetic variants. Among these, 513 populations presented selective scans, clear evidence of adaptive evolution. A high concentration of mutations occurred in Gyra, a gene associated with resistance to fluoroquinolone.

Among the 513 evolving populations, radical genetic changes have frequently occurred in Gyra, a central gene for fluoroquinolone resistance. Sixty-three populations of 34 participants presented gyra mutations, which generally manifest themselves independently within individuals. Almost 10% of the initially sensitive bacterial populations have acquired resistance through these mutations.

Once established, gyra swallows have persisted beyond 10 weeks and should remain detectable up to a year. Additional mutations associated with resistance occurred in other genes, although these events are less common and have appeared in fewer species.

The resistance was more likely to emerge in populations which were abundant before treatment and experienced significant reductions during exposure, the identification of a condition correlated with higher chances of evolutionary change.

The resistance mutations did not come with fitness costs, allowing the resistant strains to maintain a dominant population after the conclusion of treatment. The targeted sequencing has shown no evidence of the resistance of resistance. Gyra mutations only represented part of the observed resistance, suggesting additional mechanisms.

Based on the results, even the use of short -term antibiotics can cause resistance mutations that persist in the human intestine for months after the end of treatment. Mutations arise independently between bacterial species and do not engage a measurable fitness cost, allowing the resistant strains to remain widespread.

Intestinal microbes have proven to be capable of the evolution of resistance without previous infection. Commensal populations can therefore act as reservoirs of resistance lines which could transfer to pathogenic bacteria by the transfer of horizontal genes beyond interaction with antibiotics.

Because the resistance has evolved predictably according to the size of the population, it allows the possibility of predict the results of the resistance if the starting population is known before treatment. Experiences with different adjutants of start -up populations and types of treatment are necessary to fully extend this predictive modeling.

Monitoring of microbial composition and abundance before and during treatment could help guide a more precise use of antibiotics, reduce the long -term risks associated with resistance and improve the overall stewardship of the use of antibiotics.

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