Eurosurveillance - Volume 25, Issue 45, 12 November 2020

The rapid increase of bacterial antibiotic resistance could soon render our most effective method to address infections obsolete. Factors influencing pathogen resistance prevalence in human populations remain poorly described, though temperature is known to contribute to mechanisms of spread.

To quantify the role of temperature, spatially and temporally, as a mechanistic modulator of transmission of antibiotic resistant microbes.

An ecologic analysis was performed on country-level antibiotic resistance prevalence in three common bacterial pathogens across 28 European countries, collectively representing over 4 million tested isolates. Associations of minimum temperature and other predictors with change in antibiotic resistance rates over 17 years (2000–2016) were evaluated with multivariable models. The effects of predictors on the antibiotic resistance rate change across geographies were quantified.

During 2000–2016, for Escherichia coli and Klebsiella pneumoniae, European countries with 10°C warmer ambient minimum temperatures compared to others, experienced more rapid resistance increases across all antibiotic classes. Increases ranged between 0.33%/year (95% CI: 0.2 to 0.5) and 1.2%/year (95% CI: 0.4 to 1.9), even after accounting for recognised resistance drivers including antibiotic consumption and population density. For Staphylococcus aureus a decreasing relationship of −0.4%/year (95% CI:  −0.7 to 0.0) was found for meticillin resistance, reflecting widespread declines in meticillin-resistant S. aureus across Europe over the study period.

We found evidence of a long-term effect of ambient minimum temperature on antibiotic resistance rate increases in Europe. Ambient temperature might considerably influence antibiotic resistance growth rates, and explain geographic differences observed in cross-sectional studies. Rising temperatures globally may hasten resistance spread, complicating mitigation efforts.

Antimicrobial resistance (AMR) is one of the most important challenges in modern clinical practice. The European regulatory network has a strategy to support prevention of AMR by applying specific referral procedures.

The aim of this study was to evaluate post-authorisation changes made in the product information of key antibiotics that underwent referral procedures between 2007 and 2020.

In a comprehensive analysis of the changes made for antibiotics, we extracted information on changes from the European Commission community register of medicinal products and the European Medicines Agency’s database for antibiotics that went through referrals. Changes made in the specific sections of the summary of product characteristics of each referral procedure were scrutinised.

We identified 15 antibiotics from seven classes of antibiotics during the study period. The outcome of all referrals included the restriction of antibiotic use. Therapeutic indications were revised for all antibiotics, with septicaemia and gonorrhoea most common diseases removed. Posology and/or method of administration was updated for all; the majority of referrals included adjustment of dosage for specific populations. Information on contraindication (most regarding hypersensitivity) and information on warnings was amended for all referrals.

Our findings highlight the importance of the regulatory actions. The changes made in the product information aim to ensure appropriate use. Ongoing harmonisation activities are likely to lead to further refinements and restrictions on individual antibiotics in support of rational use. However, further research is required to examine the impact of post-referral label changes on the clinical practice.