28 Chapter 2 SDRMs The percentage of invasive isolates with MRSA declined in both Ireland and the UK between 2011 and 2020. The decline in Ireland and the UK is likely a result of the introduction of guidelines on the prevention and control of MRSA in 2007 and of multiple interventions including hygiene protocols and mandatory reporting of MRSA, respectively (21,22). For all three SDRMs, Italy, Poland and Spain have the highest prevalences among the countries in our study. These three countries also have a higher volume of antibiotic prescribing as expressed in DDD, and a higher ASP as represented by ASI. The higher prevalence of an SDRM is a likely consequence of the high volume of antibiotic prescribing and will lead to prescribing of more broad-spectrum antibiotics. Physicians often assume drug-resistant micro organisms are at play when treating bacterial infections in locations where drug-resistant micro organisms are known to be an issue. This encourages prescribing broad-spectrum antibiotics, often supported by guidelines advising this course. The resulting evolutionary pressure on the microbiome leads to increased selection of antimicrobial resistance. This vicious circle of prescribing more and broader spectrum antibiotics can lead to a point of no return when few antibiotics suitable for empirical use remain. Proxy indicators of ASP The levels of DDD and ASI varied between countries. Primary care practitioners in Italy and Spain prescribed twice the volume of antibiotics compared with their colleagues in Denmark, The Netherlands and Sweden, but the cumulative ASI was three times higher in Italy and Spain. Furthermore, the DDD in Spain and Italy was comparable to those of Ireland and Poland for the year 2020, whereas the ASI in 2020 was 1.5 times higher in Spain and Italy. These differences may be largely explained by the very high number of prescriptions for penicillin combinations and quinolones in Italy and Spain in primary care. Both groups are broad-spectrum antibiotics and have high ASIs of 6 and 8, respectively. The cumulative ASI seems to correlate better with the prevalence of a SDRM than does total antibiotic consumption expressed in DDD, as illustrated by data from Ireland and Italy. The DDD of Italy was only slightly higher than that of Ireland, but the prevalence of the selected SDRMs in Italy was significantly higher (Figure 2). Further, the ASI in Italy was much higher than that of Ireland and more strongly correlated with the prevalence of an SDRM (Figure 5 and S4). MRSA and S. pneumoniae showed the strongest associations with ASI, with standardized coefficients of 0.94 and 0.91,
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