Impact of generic market entry on the consumption of last-resort antibiotics in six European countries

Objectives: Excessive antibiotic use drives antimicrobial resistance. Patent expiry and subsequent generic market entry (GME) is suggested to alter antibiotic consumption, but evidence is limited. We examined GME impact on the use of selected antibiotics, including WHO "Reserve" agents, in six European countries. Methods: We conducted a retrospective multicountry analysis using IQVIA MIDAS® data (hospital and retail consumption panels: Austria, France, Germany, Italy, Spain; Hospital consumption only: Belgium) from 2012 to 2021. Substances included daptomycin, linezolid, tigecycline, teicoplanin, and moxifloxacin. GME was defined in each country as the time of the first consumption of non-originator products. Hospital consumption was expressed in defined daily doses (DDD) per 1,000 discharges. Associations between GME and antibiotic use were assessed through segmented linear regression modelling. Results: The impact of GME varied by antibiotic, country, and sector. Hospital consumption of daptomycin increased significantly post-GME in all countries, with median rates from 8.8 to 63.9 DDD/1,000 discharges. Linezolid use rose significantly in four countries, with rates between 24.7 and 110.4 DDD/1,000 discharges. Tigecycline and teicoplanin showed heterogeneous patterns. By contrast, hospital and retail consumption of moxifloxacin showed predominantly decreasing trends, though not consistently significant, with marked country variation. Conclusions: GME did not consistently drive higher antibiotic consumption while consumption trends were not fully explained by epidemiological factors or resistance patterns, either. The sustained post-GME rise in use of daptomycin and linezolid is concerning, given their reserve status, and suggests, that for last-resort agents, generic availability may undermine stewardship objectives. In contrast, declines in moxifloxacin consumption appear more strongly influenced by European Medicines Agency safety restrictions than by GME. These findings indicate that GME constitutes a contextual risk factor rather than a deterministic driver of increased antibiotic use and demonstrate that robust regulatory interventions can counterbalance factors shaping prescribing patterns, including structural cost effects following GME.