Antibiotic resistance tends to stabilize over time, according to Sonja Lehtinen, PhD, from the University of Lausanne and colleagues. The team published its study, “The evolution of antibiotic resistance in Europe, 1998–2019,” in PLOS Pathogens.
Antibiotic resistance is a major public health concern, contributing to an estimated five million deaths per year, point out the scientists. Understanding long-term resistance patterns could help public health researchers to monitor and characterize drug resistance as well as inform the impact of interventions on resistance.
In this study, researchers analyzed drug resistance in more than three million bacterial samples collected across 30 countries in Europe from 1998 to 2019. Samples encompassed eight bacteria species important to public health, including Streptococcus pneumoniae, Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae.
They found that while antibiotic resistance initially rises in response to antibiotic use, it does not rise indefinitely. Instead, resistance rates reached an equilibrium over the 20-year period in most species. Antibiotic use contributed to how quickly resistance levels stabilized as well as variability in resistance rates across different countries. But the association between changes in drug resistance and antibiotic use was weak, suggesting that additional, yet unknown, factors are at play.
“The evolutionary dynamics of antibiotic resistance are not well understood, particularly the long-term trajectories of resistance frequencies and their dependence on antibiotic consumption. Here, we systematically analyze resistance trajectories for 887 bug-drug-country combinations in Europe across 1998–2019, for eight bacterial species with a considerable resistance-associated public health burden,” wrote the investigators.
Analytical support for model
“Our analyses support a model in which, after an initial increase, resistance frequencies reach a stable intermediate equilibrium. The plurality (37%) of analyzed trajectories were best described as ‘stable’ (neither increasing nor decreasing). 21% of trajectories were best described as ‘stabilizing,’ i.e., showing a transition from increasing frequency to a stable plateau; 21% as decreasing and 20% as increasing.
“The antibiotic consumption in a country predicts both the equilibrium frequency of the corresponding resistance and the speed at which this equilibrium is reached. Moreover, we find weak evidence that temporal fluctuations in resistance frequency are driven by temporal fluctuations in hospital antibiotic consumption. A large fraction of the variability in the speed of increase and the equilibrium level of resistance remains unexplained by antibiotic use, suggesting other factors may also drive resistance dynamics.”
The study highlights that continued increase in antibiotic resistance is not inevitable and provides new insights to help researchers monitor drug resistance.
“When we looked into the dynamics of antibiotic resistance in many important bacterial pathogens all over Europe and in the last few decades, we often found that resistance frequency initially increases and then stabilizes to an intermediate level,” said Francois Blanquart, PhD, senior author and a researcher at the French National Center for Scientific Research (CNRS). “The consumption of the antibiotic in the country explained both the speed of initial increase and the level of stabilization.”
“In this study, we were interested in whether antibiotic resistance frequencies in Europe were systematically increasing over the long-term,” added Sonja Lehtinen, PhD, senior author and an assistant professor at the computational biology department at the University of Lausanne. “Instead, we find a pattern where, after an initial increase, resistance frequencies tend to reach a stable plateau.”