Antibiotic resistance (ABR) is currently one of the most urgent threats to global health. It is a natural phenomenon, but improper use of antibiotics is contributing to it by selecting resistance and complicating bacterial infection-control strategies. Worldwide surveillance of ABR, especially under the aegis of the WHO has been set up, and several databases have been created to record ABR worldwide, with the long-term aim of improving understanding of the causes to help tackle the phenomenon.
ABR varies considerably depending on the bacterial species, but per a 2019 study, around 1.27 million deaths worldwide were attributable globally to ABR and ABR was associated with 4.95 million deaths.
A multidisciplinary research team at the Institut Pasteur developed a statistical model and analyzed ABR data from the ATLAS database—which contains data collected since 2004 in more than 60 countries on every continent—to identify the main factors associated with worldwide ABR dynamics. "Research teams study how antibiotic resistance emerges in a bacterium in a Petri dish or in an individual, but we are currently lacking a population-level, global overview that can be used to investigate links between resistance and specific factors like national health system quality for different species of pathogenic bacteria. To understand the dynamics of antibiotic resistance, it needs to be studied at every level. That is what this study sets out to do," explains Eve Rahbé, a PhD research student in the Institut Pasteur's Epidemiology and Modeling of Bacterial Escape to Antimicrobials Unit and first author of the study.
Factors influencing antibiotic resistance within countries
The first stage of the study was to select relevant factors that could influence ABR dynamics. "Although some biological factors are known, it was also important for us to investigate hypotheses associated with socioeconomic and climate factors," explained Rahbé. A total of eleven independent factors were selected, including health system quality (based on the GHS index), antibiotic consumption, national wealth (GDP per capita), and data on travel and climate variables. Statistical models were then developed to study potential associations between the ATLAS data and the selected factors.
The analysis of global data for the period 2006–2019 initially revealed an increase in resistance to carbapenems for several species, although global trends were stable for other resistances. The study also demonstrated that the dynamics and factors associated with ABR depend on bacteria–antibiotic combinations.
Surprisingly, however, national antibiotic consumption was not significantly associated with resistance for the majority of bacteria tested (except for quinolone consumption for fluoroquinolone-resistant Escherichia coli and Pseudomonas aeruginosa and carbapenem consumption for carbapenem-resistant Acinetobacter baumannii).
Conversely, high health system quality was associated with low levels of ABR in all the gram-negative bacteria tested. High temperatures were associated with high levels of ABR, but only for Enterobacteriaceae (E. coli and Klebsiella pneumoniae).
"This study reveals the wide range of factors leading to antibiotic resistance among different pathogenic bacteria at global level, and the need to adapt resistance control approaches to the local context (country, transmission context) and the specific bacteria-antibiotic combination," concludes Dr Philippe Glaser, head of the Institut Pasteur's Ecology and Evolution of Antibiotic Resistance Unit and co-last author of the study.
"Our statistical model can be applied to other databases, such as the WHO database. Improving understanding of resistance determinants, which differ from one country to the next and probably even vary among regions in the same country, is crucial and will be useful in adapting public health measures," concludes Lulla Opatowski, PhD, professor at the Université de Versailles Saint-Quentin-en-Yvelines and scientist in the Epidemiology and Modeling of Bacterial Escape to Antimicrobials Unit and co-last author of the study.
- This press release was originally published on the Institut Pasteur website