Identifying quantitative evidence-based parameters to monitor emerging resistance to new antibiotics

BACKGROUND: Antimicrobial resistance (AMR) has a major public health burden, and newly-approved molecules have shown fast emerging of resistance. This study aims at assessing and developing an innovative framework to monitor and benchmark emerging resistance to new antibiotics in Europe. METHODS: Within the European ECRAID-Base project and the EPI-Net platform, data were extracted at two levels: reporting of emerging resistance to the 12 new antibiotics approved by EMA since 2012 and related outbreaks, and active resistance monitoring in national surveillance systems in 32 European countries. The burden of emerging resistance was measured through the following indicators: time lag between approval and first resistance report, average number of outbreaks, trend in the number of yearly publications standardised by the logarithm of the total number and weighted by the pooled resistance rate, and inclusion of new antibiotics in national surveillances. RESULTS: Overall, 956 articles reported resistance to new antibiotics since 2012. Resistance to ceftolozane-tazobactam (CLZ-TAZ) was the most reported, followed by ceftazidime-avibactam (CAZ-AVI); resistance to eravacycline and delafloxacin was less reported. For 6 antibiotics, resistance occurred within one year of approval. Out of 35 surveillance systems reviewed, only 13 (in 12 countries) included at least one new antibiotic; CLZ-TAZ and CAZ-AVI, monitored in 11 and 12 countries respectively, were the most surveyed. Resistance trends showed greater increase for imipenem-relebactam, CAZ-AVI, and meropenem-vaborbactam. Nine outbreaks were detected, including 136 patients: CAZ-AVI was responsible for the highest number of outbreaks (five). CONCLUSIONS: Resistance was detected to new antibiotics, yet very few countries have active monitoring systems to detect it. Appropriate monitoring and benchmarking of emerging resistance to new antibiotics is pivotal to support careful antibiotic policies at country and global level. KEY MESSAGES: • Emerging resistance to new antibiotics was assessed through quantitative parameters: some drug combinations would deserve further attention, given the increased resistance reports and surveillance gap. • Analysis of these parameters might suggest that combinations of existing agents are prone to developing resistance, and hence support focusing research on the development of novel-class drugs.