29 Trends in antibiotic selection pressure generated in primary care and their association with sentinel antibiotic resistance patterns in Europe 2 respectively. Particularly relevant for primary care is the strong association with S. pneumoniae because this is a very common cause of respiratory tract infections in primary care, even more so than skin infections caused by S. aureus (23). Comparison with existing literature Although ASI has been examined in institutes such as hospitals and nursing homes (24–30), we found no studies exploring this at a national level. The studies who examined ASI in hospitals and nursing homes showed that ASI gives additional insight into antibiotic prescribing patterns compared with other proxy indicators such as DDD or days of therapy, and may be useful for internal and external comparisons of institutions (24,28,29). Monitoring antibiotic consumption combined with surveillance of resistant micro organisms is advised as part of the One Health strategy (31). Most healthcare systems still use DDD as the only measure to represent the volume of antibiotic use. Strengths and limitations A strength of our study is using absolute volumes of antibiotic prescriptions in primary and hospital care when calculating the proxy indicator cumulative ASI. The proxy indicator is in this way a better representation of the ASP in a country than, for example, weighted mean volumes. The applied method of calculating the ASP is relatively simple, which makes it easily implemented in almost every country or region as a proxy indicator. A limitation of this study is that some of the prescribed antibiotics may not be directly related to increasing resistance found in a specific SDRM. However, exposure to antibiotics in general is sufficient to generate community-acquired resistant infections in members of the same community. Further, the cumulative ASI is a proxy indicator representing the level of implementation of antimicrobial stewardship and the prevalence of already existing AMR in a country. The ratio between antimicrobial stewardship and already existing AMR contributing to ASI is not deducible from our study. We used only three specific SDRMs in our study. Although using other SDRMs may lead to slightly different results, the expected trend would be similar. Because only European countries in which GPs act as gatekeepers were included in this study, the results may be less generalizable to countries with differently organized healthcare systems.
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