Quantifying the Seasonality and Modeling the Evolution in Time of Carbapenemase-Producing Enterobacteriaceae Episodes in France Over 2010-2020

Background: Carbapenemase-producing Enterobacteriaceae (CPE) cause resistant healthcare-associated infections that jeopardize healthcare systems and patient safety worldwide. The number of CPE episodes has been increasing in France since 2009 but the dynamics are still poorly understood. Methods: We used a time-series approach to analyze CPE episodes from August 2010 to November 2016 reported to the French national surveillance system. The impact of seasonality was quantified using seasonal-to-irregular ratios. Seven time-series models and three ensemble stacking models (average, convex and linear stacking) were assessed and compared to forecast CPE episodes during 2017-2020. Findings: During 2010-2016, 3559 CPE episodes were observed in France. Compared to the average yearly trend, we observed a 30% increase in the number of CPE episodes in Autumn. We noticed a 1-month lagged seasonality of non-imported episodes compared to imported episodes. Average stacking gave the best forecasts and predicted an increase during 2017-2020 with a peak up to 345 CPE episodes (95% PI[124-1158], 80% PI[171-742]) in September 2020. Interpretation: The observed seasonality of CPE episodes sheds light on potential factors associated with the increased frequency of episodes which need further investigations. Our model predicts that the number of CPE episodes will continue to rise in the coming years in France, mainly due to local dissemination, associated with bacterial carriage of patients in the community which is becoming an immediate challenge to help controlling the outbreak. Funding Statement: French national research agency (ANR) through the SPHINx project. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: Ethical and data access approvals for the present study were obtained in accordance with French legislation. The data on CPE episodes used in this study were anonymized and aggregated at the hospital level, which did not permit to identify colonized or infected cases. The study protocol was reviewed and accepted by the French national public health agency, which provided the data.