WHO Regional Office for Europe Antimicrobial Medicines Consumption (AMC) Network: AMC data 2020–2021

AMC data 2020–2021 WHO Regional Office for Europe Antimicrobial Medicines Consumption (AMC) Network Abstract This report presents analyses of data on antimicrobial medicines consumption collected from non-European Union countries in the WHO European Region – 13 countries provided 2020 data and 10 countries provided 2021 data. The analyses show the results for key metrics of antibiotic consumption including total use, relative use of agents according to the WHO Access, Watch and Reserve (AWaRe) classification, and concordance with WHO monitoring indicators for responsible use of antibiotics. Analyses explore the possible impact of the COVID-19 epidemic on volumes and patterns of consumption of antibiotics. Keywords CONSUMPTION SURVEILLANCE ANTIBIOTICS EPIDEMIOLOGICAL MONITORING RESPONSIBLE USE OF ANTIBACTERIALS EASTERN EUROPE CENTRAL ASIA ISBN: 978-92-890-6004-2 (PDF) © World Health Organization 2023 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition: WHO Regional Office for Europe Antimicrobial Medicines Consumption (AMC) Network. AMC data 2020–2021. Copenhagen: WHO Regional Office for Europe; 2023”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization (http://www.wipo.int/amc/en/mediation/rules/). Suggested citation. WHO Regional Office for Europe Antimicrobial Medicines Consumption (AMC) Network. AMC data 2020–2021. Copenhagen: WHO Regional Office for Europe; 2023. Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data. CIP data are available at http://apps.who.int/iris. Sales, rights and licensing. To purchase WHO publications, see http://apps.who.int/bookorders. To submit requests for commercial use and queries on rights and licensing, see http://www.who.int/about/licensing. Third-party materials. If you wish to reuse material from this work that is attributed to a third party, such as tables, figures or images, it is your responsibility to determine whether permission is needed for that reuse and to obtain permission from the copyright holder. The risk of claims resulting from infringement of any third-party-owned component in the work rests solely with the user. General disclaimers. The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of WHO concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted and dashed lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by WHO in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. All reasonable precautions have been taken by WHO to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either expressed or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall WHO be liable for damages arising from its use. WHO Regional Office for Europe Antimicrobial Medicines Consumption (AMC) Network AMC data 2020–2021

iii CONTENTS Acknowledgements iv Abbreviations v Abbreviations of country names used in tables and figures v Executive summary vi 1 Introduction 1 1.1 Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1.2 The WHO Regional Office for Europe Antimicrobial Medicines Consumption (AMC) Network . . . . . . 1 1.3 Previous publications of AMC Network data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1.4 Scope and aim of this report . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 2 Methods 3 2.1 Data sources and data collection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 2.2 ATC and DDD classification systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 2.3 Antibacterial agents included in this report . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 2.4 Metrics and indicators reported . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 3 Antimicrobial medicines consumption across the AMC Network, 2020–2021 10 3.1 Estimates of volumes of consumption of antibacterials for systemic use (J01) . . . . . . . . . . . . . . . . . 10 3.2 Relative consumption of AWaRe groups of antibiotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 3.3 DU75% . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 3.4 GLASS-IT platform . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 4 Discussion 32 References 36 Annex 1 Agents included in the 2021 AWaRe index 38 iv ACKNOWLEDGEMENTS The WHO Regional Office for Europe would like to thank the members of the Antimicrobial Medicines Consumption (AMC) Network for providing antimicrobial consumption data and for their valuable contributions to this report. The database for data analysis was developed in conjunction with Public Health Expertise, Paris, France. The report was written by Dr Jane Robertson and Ms Kotoji Iwamoto of Access to Medicines and Health Products at the WHO Regional Office for Europe. The activities of the AMC Network are coordinated by the Regional Office. The financial support of the Ministry of Health, Welfare and Sport of the Kingdom of the Netherlands and the German Collaboration Programme are gratefully acknowledged. vABBREVIATIONS AMC Antimicrobial Medicines Consumption (Network) AMR antimicrobial resistance ANOVA analysis of variance (test) ATC Anatomical Therapeutic Chemical (classification system) AWaRe WHO Access, Watch and Reserve (classification) CAGR compound annual growth rate DDD defined daily dose DID defined daily doses per 1000 inhabitants per day DU75% drug utilization 75% ECDC European Centre for Disease Prevention and Control EEA European Economic Area EML WHO Model List of Essential Medicines for adults EMLc WHO Model List of Essential Medicines for children ESAC-Net European Surveillance of Antimicrobial Consumption Network EU European Union GLASS Global Antimicrobial Resistance and Use Surveillance System GLASS-AMC Global Antimicrobial Resistance and Use Surveillance System, Antimicrobial Medicines Consumption module GLASS-IT Global Antimicrobial Resistance and Use Surveillance System Information Technology Abbreviations of country names used in tables and figures ALB Albania ARM Armenia AZE Azerbaijan BIH Bosnia and Herzegovina BLR Belarus GEO Georgia KAZ Kazakhstan KGZ Kyrgyzstan MDA Republic of Moldova MKD North Macedonia MNE Montenegro RUS Russian Federation SRB Serbia SWI Switzerland TJK Tajikistan TUR Türkiye UKR Ukraine UZB Uzbekistan vi EXECUTIVE SUMMARY The WHO Regional Office for Europe Antimicrobial Medicines Consumption (AMC) Network aims to support all Member States in the WHO European Region that are not part of the European Surveillance of Antimicrobial Consumption Network (ESAC-Net) coordinated by the European Centre for Disease Prevention and Control (ECDC). AMC Network members are: Albania, Armenia, Azerbaijan, Belarus, Bosnia and Herzegovina, Georgia, Kazakhstan, Kyrgyzstan, Montenegro, North Macedonia, the Republic of Moldova, the Russian Federation, Serbia, Switzerland, Tajikistan, Türkiye, Ukraine and Uzbekistan. This is the fifth AMC Network report, with analyses conducted using 2020 data from 13 AMC Network countries and 2021 data from 10 countries. The report focuses on cross-national analyses and trends from 2019 to 2021, which might reflect the impact of the early phases of the COVID-19 pandemic. The 2021 WHO Access, Watch and Reserve (AWaRe) classification of antibiotics is applied and the WHO national monitoring target of at least 60% of total consumption being Access agents is assessed. The utilization of antibacterial substances accounting for 75% of consumption (the drug utilization 75% (DU75%)) measured in defined daily doses, is calculated for oral and parenteral formulations separately. The impact of using different population estimates in the Global Antimicrobial Resistance and Use Surveillance System (GLASS) is explored. Key findings Data on total consumption of antibacterials for systemic use (Anatomical Therapeutic Chemical (ATC) classification group J01) were available for 13 countries in 2020 and 10 in 2021. In 2020, consumption of J01 antibacterials ranged from 9.0 defined daily doses per 1000 inhabitants per day (DID) (Switzerland) to 34.3 DID (Kyrgyzstan), with a median consumption of 19.5 DID and a population- weighted mean consumption of 21.8 DID. The comparable estimates for 2019 were 10.6–33.2 DID, a median consumption of 19.6 DID and a population-weighted mean consumption 21.2 DID. Of 10 countries with 2021 data, consumption ranged from 8.6 DID (Switzerland) to 34.4 DID (Serbia), with a median consumption of 19.3 DID and a population-weighted mean consumption of 20.3 DID. Together, the three years of data (2019–2021) suggest there was increased consumption of J01 antibacterials in 2020 and the early phases of the COVID-19 pandemic, and subsequent reductions in 2021. However, this pattern was not consistent across all countries. Data from Belarus, the Russian Federation and Tajikistan followed the pattern, showing increases in consumption from 2019 to 2020, then falling consumption levels in 2021. Consumption in Serbia increased in each successive year from 26.6 DID in 2019, to 29.2 DID in 2020 and to 34.4 DID in 2021. In Türkiye, total consumption fell substantially between 2019 and 2020 (33.2 DID to 25.8 DID) before increasing in 2021 to 28.3 DID. Further investigation at the country level is needed to understand the reasons for the patterns seen and the possible contribution of the COVID-19 pandemic to the estimates. AMC population-weighted estimates for consumption of pharmacological subgroups of J01 antibacterials in 2019, 2020 and 2021 showed increased relative consumption of the macrolides, lincosamides and streptogramins group (J01F), increasing from 14% of total J01 consumption in 2019 to 20% in 2020, then falling to 15% in 2021. The macrolides group includes azithromycin, which was promoted as a treatment for COVID-19 infection. Subsequent clinical trials failed to demonstrate any clinical benefits of azithromycin in reducing the time to recovery or the risk of hospitalization for people vii with suspected COVID-19 in the community. This trial evidence may have contributed to the reduced consumption of J01F antibacterials and, in particular, azithromycin in 2021. Ten countries had consumption estimates available for all years 2014–2021. Three showed statistically significant increases in consumption of J01 antibacterials over the eight years of data collection – Azerbaijan (compound annual growth rate (CAGR) +8.4%), Bosnia and Herzegovina (+3.1%) and the Russian Federation (+2.8%). Three countries showed statistically significant reductions in consumption over time – North Macedonia (−0.9%), Switzerland (−3.6%) and Türkiye (−2.9%). AMC Network population-weighted estimates of the relative consumption of Access, Watch and Reserve classification antibacterials from 2019 to 2021 show that Access agents represented 50% of consumption in 2019, 47% in 2020 and 50% in 2021. Watch group antibiotics constituted 46%, 52% and 49% of total consumption in the same years. Consumption of Reserve agents and unclassified antibacterials was low in all three years. Most countries showed patterns similar to the Network averages, namely decreases in relative consumption of Access agents from 2019 to 2020 and increases in 2021. This pattern of consumption is likely to be attributable to the increased consumption of Watch group macrolides, including azithromycin, in 2020 and reductions in 2021. In 2019, five AMC Network countries met WHO’s suggested national target of 60% of total consumption of antibacterials being derived from the Access list. Only Switzerland achieved this target in 2020 (63%); Belarus (66%) and Switzerland (65%) met it in 2021. The number of agents constituting the DU75% – by oral substance – ranged from 5 to 10 in 2020 and 6 to 9 in 2021 across the AMC Network countries. There were six Watch agents in the population- weighted DU75% in both 2020 and 2021. The most notable change between 2019 and 2020 was the increased relative consumption of azithromycin – rising from fourth to second-most consumed oral antibiotic across the AMC Network in 2020. The pattern was consistent, with azithromycin included in the DU75% for 12 of the 13 Network countries for which data was available in 2020, ranked first most consumed antibiotic in six countries and second in a further five countries. The scope of WHO’s GLASS has widened in the past few years to include surveillance data on AMC. This module is called GLASS-AMC and the platform is called GLASS information technology (GLASS-IT) platform. Network members are transitioning to data collection via the GLASS-IT platform. Analyses are broadly similar to those conducted by the AMC Network, except that GLASS-AMC applies United Nations population estimates for its calculations. Since 2011, the AMC Network has used World Bank population estimates in calculations – apart from for Switzerland and Türkiye, where national population estimates are applied. Exploratory analyses were conducted using 2021 consumption data to examine the impact of a change in population data source (from World Bank to United Nations population estimates). In six of seven countries which have been using World Bank population estimates in calculations of antimicrobial consumption, these population estimates were lower than United Nations estimates, with the largest differences for Belarus (2.85% lower) and Serbia (7.13% lower). For Serbia, the total consumption estimate is 6.7% higher using the World Bank population estimate rather than that of the United Nations. For Switzerland and Türkiye, national population estimates are higher than United Nations estimates, 4.48% higher in the case of Türkiye. For Türkiye, this results in an estimate of total consumption of J01 antibacterials that is 4.69% lower than that derived using United Nations population data. These findings are relevant as countries move to AMC consumption calculated using the GLASS-IT platform. Those interpreting and using consumption estimates to inform national policies on access and use of antibiotics need to be aware of the data source used in the calculations, particularly in the situation that historical data based on World Bank population estimates are being compared with new GLASS-AMC estimates. The GLASS-IT platform will recalculate historical data and adjust populations used in the calculations to United Nations estimates, however this can only occur for historical data that are uploaded to the GLASS-IT platform.

11. INTRODUCTION 1 1 Background 1 Based on an alternative scenario in which all drug-resistant infections were replaced by drug-susceptible infections. 2 Based on an alternative scenario in which all drug-resistant infections were replaced by no infection. Antimicrobial resistance (AMR) is a serious threat to public health. A comprehensive analysis of regional and country-level estimates of AMR burden in the WHO European Region estimated 541 000 deaths (95% uncertainty interval 370 000–763 000) associated with bacterial AMR,1 and 133 000 deaths (90 100–188 000) attributable to bacterial AMR in 20192 (European Antimicrobial Resistance Collaborators, 2022). Ensuring prudent antimicrobial use is a key priority in an effective response to the challenges of AMR. Regular surveillance of antibiotic consumption to identify potential overuse, underuse and inappropriate use can help identify potential targets for interventions to improve antibiotic utilization. 1 2 The WHO Regional Office for Europe Antimicrobial Medicines Consumption (AMC) Network The WHO Regional Office for Europe AMC Network has been undertaking systematic surveillance of antimicrobial medicines consumption in 18 non-European Union (EU) Member States of the WHO European Region since 2011 (WHO Regional Office for Europe, 2022a). Data collection is based on the WHO Anatomical Therapeutic Chemical (ATC) classification system and defined daily doses (DDD) methodology (WHO Collaborating Centre for Drug Statistics Methodology, 2022). The following Member States are currently engaged in the AMC Network: Albania, Armenia, Azerbaijan, Belarus, Bosnia and Herzegovina, Georgia, Kazakhstan, Kyrgyzstan, Montenegro, North Macedonia, the Republic of Moldova, the Russian Federation, Serbia, Switzerland, Tajikistan, Türkiye, Ukraine and Uzbekistan. 1 3 Previous publications of AMC Network data There have been four published reports of AMC Network data. The first report covered data for 2011–2014, and was published in 2017 (WHO Regional Office for Europe, 2017). An analysis of data for 2011–2017 for 17 Network members was published in 2020 (WHO Regional Office for Europe, 2020); a third report of AMC Network data for 2014–2018 was published in 2021 (WHO Regional Office for Europe, 2021); and 2019 data for 14 AMC Network countries was published in 2022 (WHO Regional Office for Europe, 2022a). Analyses of AMC Network data have also been published in the peer-reviewed literature: a cross- national comparison of 2015 AMC data for 16 members of the AMC Network was published in 2019 (Robertson et al., 2019) and a comparison of AMC Network data with that of the European Surveillance of Antibiotic Consumption Network (ESAC-Net) coordinated by the European Centre for Disease Prevention and Control (ECDC) using data for 2014–2019 was published in 2021 (Robertson et al., 2021). 2ANTIMICROBIAL MEDICINES CONSUMPTION (AMC) NETWORK 1 4 Scope and aim of this report This report extends the reporting of the AMC Network, presenting data for 2020 (13 countries) and 2021 (10 countries) from members that submitted data and gave permission for it to be published. Cross-national comparisons are presented. Comparisons with 2019 consumption data are also made to examine the possible impacts of the COVID-19 pandemic on the volumes and patterns of consumption of antibacterial agents. The analyses apply the 2021 Access, Watch and Reserve (AWaRe) classification of antibiotics (WHO, 2021a, 2021b), and assess concordance with the WHO global/national target that 60% of total consumption is Access agents (WHO Executive Board, 2018). In addition, analyses report on the antibacterial substances accounting for 75% of consumption – the drug utilization 75% (DU75%) (Zarb et al., 2011). Finally, exploratory analyses are conducted to examine the potential impact of a change of source of population data on consumption estimates derived using the Global Antimicrobial Resistance and Use Surveillance System (GLASS) platform. 32. METHODS 2 1 Data sources and data collection 3 IQVIA is a human data science company which has assets in data, technology and advanced analytics with an interest in health care and human health. 2 1 1 Data sources AMC Network countries mostly rely on import data – using customs records and declaration forms, supplemented with sales records from market authorization holders, local manufacturing estimates, wholesaler records, commercial data and, in some cases, reimbursement data sources – to derive estimates of consumption (Table 1). In some countries, data are not available for all years examined. Table 1 Sources of data used for consumption estimates, 2014–2021 Country 2014 2015 2016 2017 2018 2019 2020 2021 Albania I I I I I I – – Armenia I, M I, M I, M I, M I, M I, M I, M – Azerbaijan I I I I I I I I Belarus I, M I, M I, M I, M I, M I, M I, Md I, M Bosnia and Herzegovina S, M S, M S, M S, M S, M S, M S, M S, M Georgia I I I I I I I – Kazakhstan – S S S S – – – Kyrgyzstan – I, S I, S I, S I, S I, S I, S – Montenegro S S S S S S S S North Macedoniaa R R R R R R R R Republic of Moldova I, M I, M I, M I, M I, M – – – Russian Federation S S S S S S S S Serbia S S S S S S S S Switzerlandb S S S S S S S S Tajikistan I, C I, C I, C I, C I, C I, C I, C I, C Türkiyec S S S S S S S S Ukraine S S S S S – – – Uzbekistan – – I, S I, S I, S I, S – – Notes: C: certification records; I: import records; M: manufacturing records; R: reimbursement data; S: sales data. a Reimbursement data cover the community sector only. b Estimates derived from IQVIA Sell-In data (sales data from wholesalers to pharmacy), self- dispending doctors and hospital, therefore covering outpatient and inpatient consumption.3 c Türkiye uses wholesalers’ records from the pharmaceutical track and trace system. d During the pandemic alternative suppliers were used to procure some medicines. Data from these suppliers were not included in these analyses. Therefore, estimates of total consumption and consumption of specific agents used to manage COVID-19 including azithromycin, clarithromycin and oseltamivir will be underestimates of actual consumption. Source: AMC Network. 4ANTIMICROBIAL MEDICINES CONSUMPTION (AMC) NETWORK 2 1 2 Data collection Data collection is based on a standardized protocol that is aligned with the WHO methodology for a global programme on surveillance of antimicrobial consumption (WHO, 2017) and the GLASS methodology for surveillance of national antimicrobial consumption (WHO, 2020). Data are collected at the product level (proprietary and generic products) and comprise information on the active substance(s) of the product, route of administration, strength per unit, number of units per package and total number of packages consumed. Data collection is facilitated by means of a standard Excel template with functions to calculate volume and consumption for each product. 2 2 ATC and DDD classification systems The AMC Network uses the ATC classification system to distinguish between pharmacological subgroups and substance levels of antimicrobials, and uses DDD as the primary measurement metric (WHO Collaborating Centre for Drug Statistics Methodology, 2022). The DDD is the assumed average maintenance dose per day for a medicine used for its main indication in adults. A DDD is only assigned for medicines that have an ATC code. The DDD, however, is only a technical unit of use and does not necessarily reflect the recommended or average prescribed daily dose. The DDDs for anti-infectives are as a rule based on use in infections of moderate severity, but some anti-infectives are used only in severe infections and their DDDs are assigned accordingly. There are no separate DDDs for children, which makes the DDD estimates for paediatric formulations more difficult to interpret. Only medicines with an assigned ATC code and DDD are included in the analyses reported here. In several countries in the AMC Network, various medicines without such codes are consumed by the population. Exclusion of these medicines means that data are missing in the numerator for the calculation, and the resulting DDD per 1000 inhabitants per day (DID)estimates will underestimate total antimicrobial consumption in the country. 2 2 1 Population estimates Population-adjusted estimates of consumption are derived by dividing the total number of DDDs at the desired ATC code level by the relevant population. For total consumption, this is the national population, which is assumed to reflect the potential scope of usage of the product. Since 2011, the AMC Network has applied population estimates from the World Bank for the calculations, except for North Macedonia where the population eligible to receive medicines under the health insurance fund is used, and Switzerland and Türkiye, where national population estimates are applied. In the case of Switzerland, national estimates are used for the sake of consistency with the estimates published in their national reports; in the case of Türkiye, national estimates account for the large refugee populations in that country that are not reflected in World Bank population estimates. For global reporting using the GLASS information technology (GLASS-IT) platform, WHO uses United Nations population statistics as standardized population estimates for all Member States. The GLASS methodology notes that for national reporting, countries should use the best estimates of the population covered by the surveillance system. The impact of changing from World Bank to United Nations population statistics for deriving consumption estimates is explored in section 3.4.1 of this report. 5METHODS 2 3 Antibacterial agents included in this report The main analyses presented here are for the antibacterials for systemic use (ATC group J01) and related pharmacological subgroups. Data on additional antimicrobials outside the ATC J01 group are also included in the calculation of antimicrobial consumption according the 2021 WHO AWaRe classification (WHO, 2021b); these comprise: neomycin (A07AA01), streptomycin oral (A07AA04), polymyxin B oral (A07AA05), kanamycin oral (A07AA08), vancomycin oral (A07AA09), colistin oral (A07AA10), rifamixin (A07AA11), fidaxomicin (A07AA12), rifamycin oral (A07AA13), rifampicin (J04AB02), rifamycin intravenous (J04AB03), rifabutin (J04AB04), metronidazole oral (P01AB01), tinidazole oral (P01AB02), ornidazole oral (P01AB03) and secnidazole (P01AB07) (Table 2). Additions new to the 2021 AWaRe index (beyond those included in the J01 category) are fidaxomicin (Watch), ornidazole oral (Access), rifamycin oral (Watch), secnidazole (Access) and tinidazole oral (Access). None of these agents is listed on the WHO Model List of Essential Medicines for adults/ children (EML/EMLc) 2021 (WHO, 2021a). Table 2 Antibacterials included in the analyses Class of agents ATC code (medicine) Antibacterials for systemic use Pharmacological subgroups of J01 Tetracyclines Amphenicols Beta-lactam antibacterials, penicillins Other beta-lactam antibacterials Sulfonamides and trimethoprim Macrolides, lincosamides and streptogramins Aminoglycoside antibacterials Quinolone antibacterials Combinations of antibacterials Other antibacterials J01 J01A J01B J01C J01D J01E J01F J01G J01M J01R J01X Antibiotics for intestinal tract A07AA01 (neomycin) A07AA04 (streptomycin) A07AA05 (polymyxin B) A07AA08 (kanamycin) A07AA09 (vancomycin) A07AA10 (colistin) A07AA11 (rifaximin) A07AA12 (fidaxomicin) A07AA13 (rifamycin oral) Antimycobacterials J04AB02 (rifampicin) J04AB03 (rifamycin) J04AB04 (rifabutin) Nitroimidazole derivatives P01AB01 (metronidazole) P01AB02 (tinidazole) P01AB03 (ornidazole) P01AB07 (secnidazole) 2 4 Metrics and indicators reported 2 4 1 Measures of volume and relative consumption Total numbers of DDDs for each product are aggregated to give the total number of DDDs at the desired ATC code level. The number of DDDs provides a measure of the extent of use, but for comparative purposes these data are usually adjusted for population size or population group, depending on the medicines of interest and the level of disaggregation of data that is possible. For most antibacterials, DID is calculated for the total population, including all age and gender groups. 6ANTIMICROBIAL MEDICINES CONSUMPTION (AMC) NETWORK Patterns of consumption in 2020 and 2021 by ATC 3 subgroups of J01 antibacterial agents and by route of administration (oral and parenteral) were assessed. Both volumes in DID and measures of relative consumption, expressed as a percentage of total consumption of groups of antimicrobials, were derived for pharmacological subgroups of J01. 2 4 1 1 Total consumption in DID The DID is the primary indicator of antibiotic consumption in countries as defined by the European Commission and WHO (European Centre for Disease Prevention and Control et al., 2017) and is a key indicator reported in the first WHO global report on antimicrobial consumption (WHO, 2018). 2 4 1 2 Route of administration Oral administration is generally regarded as the most acceptable and economical method of administration of antimicrobials. Oral medication is associated with fewer complications, lower health-care costs and earlier hospital discharge. It nevertheless must be recognized that there may also be cultural and medical practice traditions that favour the use of parenteral formulations in some settings. This report includes analyses of use of oral and parenteral formulations for J01 medicines. Where consumption of parenteral formulations is comparatively high, there may be opportunities to increase the use of oral formulations without any loss of clinical efficacy. 2 4 1 3 Consumption of pharmacological subgroups (ATC 3rd level) Absolute and relative consumption figures for pharmacological subgroups of J01 (ATC 3rd level) are presented in this report. 2 4 2 Trends in total consumption over time To illustrate changes in rates in antimicrobial consumption over time, the compound annual growth rate (CAGR) of total antibiotic consumption was calculated for each participating country. This reflects the average annual change as a proportion (%) of the consumption in the starting year. CAGRs were estimated for countries that had five years of data available. Linear regression was used for presenting trends in consumption for each participating country and evaluated using analysis of variance (ANOVA) tests. P values ≤ 0.05 were considered statistically significant. 2 4 3 WHO AWaRe classification The AWaRe classification of antibiotics was developed in 2017 by the WHO Expert Committee on Selection and Use of Essential Medicines as a tool to support antibiotic stewardship efforts at local, national and global levels. Antibiotics are classified into three groups, Access, Watch and Reserve, taking into account the impact of different antibiotics and antibiotic classes on AMR, to emphasize the importance of their appropriate use. The characteristics of these groups are shown in Table 3. Subsequent updates to the AWaRe classification in 2019 (WHO, 2019) and 2021 (WHO, 2021b) have resulted in the classification of a total of 258 antibiotics. 7METHODS The AWaRe classification is a useful tool for monitoring antibiotic consumption, defining targets and monitoring the effects of stewardship policies that aim to optimize antibiotic use and curb AMR. The WHO Thirteenth General Programme of Work 2019–2023 includes a country-level target of at least 60% of total antibiotic consumption being Access group antibiotics (WHO, 2018, 2021b). The proportions of consumption (%) according to the AWaRe classification are presented in this report. The agents listed in the 2021 AWaRe index are shown in Annex 1. Table 3 WHO categories of antibiotics – descriptions Group Definition Access agents This group includes antibiotics that have activity against a wide range of commonly encountered susceptible pathogens while also showing lower resistance potential than antibiotics in the other groups. Watch agents This group includes antibiotics that have higher resistance potential and includes most of the highest priority agents among the Critically Important Antimicrobials for Human Medicine and/ or antibiotics that are at relatively high risk of selection of bacterial resistance. Antibiotics in the Watch group should be prioritized as key targets of stewardship programmes and monitoring. Reserve agents This group includes antibiotics and antibiotic classes that should be reserved for treatment of confirmed or suspected infections due to multidrug-resistant organisms. Antibiotics in the Reserve group should be treated as “last resort” options; they should be accessible, but their use should be tailored to highly specific patients and settings when all alternatives have failed or are not suitable. These medicines could be protected and prioritized as key targets of national and international stewardship programmes involving monitoring and utilization reporting to preserve their effectiveness. Unclassified These are medicines not specifically identified in the groups described above. Some unclassified agents are included in WHO’s list of “not recommended antibiotics”. The “not recommended” agents are the fixed-dose combinations of multiple broad-spectrum antibiotics whose use is neither evidence-based nor recommended in high-quality international guidelines. WHO does not recommend their use in clinical practice. 2 4 4 WHO global monitoring indicator WHO has proposed a global monitoring indicator that by 2023, 60% of all antibiotics consumed should come from the Access group, those at lowest risk of resistance (WHO, 2021b). The proportion of total consumption that comprised Access agents was calculated for each year of analysis from 2014 to 2021. The number of countries reaching the WHO global monitoring target in 2019 and across each of the years assessed is reported. 2 4 5 DU75% In the 2017 and 2020 AMC Network reports, the 10 most consumed oral formulations and 10 most consumed parenteral formulations were presented. These analyses are based on the observations of ESAC-Net and other analyses, that consumption tends to be concentrated in a relatively small number of agents. In the 2021 AMC Network report, the DU75% was calculated. This metric was considered in the WHO global report on antimicrobial consumption (WHO, 2018), where results were stratified by route of administration (oral and parenteral formulations) and reported by region. All substances that appeared on the DU75% lists in countries within a region were compiled into a region-specific list for oral substances and parenteral substances, respectively. 8ANTIMICROBIAL MEDICINES CONSUMPTION (AMC) NETWORK The DU75% for 2018 was reported by country and across networks in the 2021 joint publication on AMC data from ESAC-Net and the WHO Regional Office for Europe (Robertson et al., 2021). In this report, the DU75% is calculated for oral and parenteral formulations separately. Results are shown as the ranking of consumption at substance level (ATC 5th group level). In addition to reporting the numbers of antibacterial agents in the DU75% segment, this report categorizes the agents in this segment according to the AWaRe classification. This facilitates identification of restricted and special use antibacterials that may be consumed widely and be potential targets for stewardship activities. 2 4 6 Summary measures applied to cross-national comparisons AMC Network summary data are presented using arithmetic and population-weighted mean estimates. Arithmetic means for total consumption are derived by summing the national estimates for total consumption and dividing by the number of countries contributing data to the calculation. Population-weighted estimates for total consumption are calculated by multiplying the DID for each country with the corresponding population, summing the country estimates and dividing the total DDDs by the total population of participating countries (European Centre for Disease Prevention and Control, 2021). Using similar methods, population-weighted estimates are calculated for the relative consumption of AWaRe group agents and for components of the DU75% in the AMC Network. 2 4 7 Metrics reported in the analyses The key metrics used in analyses and included in this report are summarized in Table 4. 9METHODS Table 4 Metrics used in analyses and included in this report Category Unit Estimates of volumes of consumption of antibacterials for systemic use (J01) Total consumption of J01 antibacterials by route of administration DID Total consumption of J01 antibacterials by pharmacological subgroup (ATC3): - tetracyclines (J01A) - amphenicols (J01B) - beta-lactam antibacterials, penicillins (J01C) - other beta-lactams (includes cephalosporins) (J01D) - sulfonamides and trimethoprim (J01E) - macrolides, lincosamides and streptogramins (J01F) - quinolone antibacterials (J01M) - other J01 antibacterials (J01G, J01R, J01X) DID Relative consumption of J01 antibacterials by subgroup Relative consumption of J01 antibacterials by pharmacological subgroup % Relative consumption of WHO Access, Watch, Reserve antibioticsa Relative consumption of Access, Watch and Reserve group agents % Concordance with WHO global monitoring indicator Proportion of total consumption that is Access agents % DU75% DU75% – oral formulation Rank DU75% – parenteral formulation Rank Summary metrics reported in cross-national comparisons Arithmetic mean estimates of: - total consumption of J01 antibacterials - consumption of pharmacological subgroups (ATC3) - consumption of agents according to AWaRe classification DID DID, % DID, % Population-weighted mean estimates of: - total consumption of J01 antibacterials - consumption of pharmacological subgroups (ATC3) - consumption of agents according to AWaRe classification - agents comprising the DU75% DID DID, % DID, % Rank a Total consumption of antibiotics for this calculation includes: J01 antibacterials, neomycin (A07AA01), streptomycin (A07AA04), polymyxin B (A07AA05), kanamycin (A07AA08), vancomycin (A07AA09), colistin (A07AA10), rifamixin (A07AA11), fidaxomicin (A07AA12), rifamycin oral (A07AA13), rifampicin (J04AB02), rifamycin intravenous (J04AB03), rifabutin (J04AB04), metronidazole (P01AB01), tinidazole (P01AB02), ornidazole (P01AB03) and secnidazole (P01AB07). Joint interpretation of these metrics will help to identify broad areas for national antibiotic stewardship and guideline development, even when information about indication is not available. Previous AMC Network reports have described several limitations to the data sources used. Even with these limitations, the variability of consumption patterns within and between countries provides a basis for further investigation to better understand how antibacterials are used in practice. The consumption data need to be interpreted with an understanding of the local context, taking account of changes in regulations (including enforcement of prescription-only access), data sources, resistance patterns and the potential impact of interventions to change practices. 10 ANTIMICROBIAL MEDICINES CONSUMPTION (AMC) NETWORK 3. ANTIMICROBIAL MEDICINES CONSUMPTION ACROSS THE AMC NETWORK, 2020–2021 In this chapter, comparisons are made across AMC Network members providing consumption data for 2020 (13 countries) and 2021 (10 countries). Where possible, comparisons with 2019 (14 countries) are provided. 3 1 Estimates of volumes of consumption of antibacterials for systemic use (J01) 3 1 1 Total consumption in 2020 Consistent with previous analyses of AMC Network data, there is wide variability in reported total consumption of J01 antibacterials for systemic use (ATC class J01) for 2020 – ranging from 34.3 DID (Kyrgyzstan) to 9.0 DID (Switzerland) (Fig. 1 and Table 5). This compares to a range of 33.2 DID (Türkiye) to 10.6 DID (Switzerland) in 2019. The median consumption in 2020 was 19.5 DID (in 2019 it was 19.6 DID across 14 network members). The arithmetic and population-weighted mean totals of J01 consumption in 2020 were 21.4 and 21.8 DID, respectively (compared to 19.6 and 21.2 DID in 2019). 3 1 2 Route of administration in 2020 The extent of consumption of parenteral formulations varied widely, from 6% in Bosnia and Herzegovina and Türkiye, up to 43% in Kyrgyzstan (Table 5). North Macedonia data relate to community consumption of oral antibiotics only. 11 ANTIMICROBIAL MEDICINES CONSUMPTION ACROSS THE AMC NETWORK, 2020–2021 Table 5 Total consumption of J01 antibacterials by route of administration, 2020 Route of administration DID (% of totala) KGZ TJK SRB MNE BLR TUR RUS BIH ARM MKDb GEO AZE SWI WHO/AMCc Oral J01 19.5 (57) 17.8 (59) 26.7 (91) 25.4 (91) 23.2 (89) 24.3 (94) 17 (87) 18.1 (94) 15.2 (88) 14.5 (100) 13.1 (92) 8.5 (79) 8.1 (91) 19.1 (88) Parenteral J01 14.8 (43) 12.2 (41) 2.5 (9) 2.4 (9) 2.8 (11) 1.5 (6) 2.5 (13) 1.2 (6) 2.2 (12) – 1.2 (8) 2.2 (21) 0.8 (9) 2.7 (12) Totala 34.3 30.0 29.2 27.8 25.9 25.8 19.5 19.2 17.4 14.5 14.3 10.8 9.0 21.8 a Total amounts and percentages may vary slightly due to rounding. b Community consumption. c WHO/AMC population-weighted mean for countries of the AMC Network. 3 1 3 Total consumption in 2021 Total consumption of antibacterials for systemic use (ATC class J01) in 2021 is examined by route of administration (oral and parenteral formulations) (Fig. 2 and Table 6). Consumption of J01 antibacterials in 2021 across the 10 countries ranged from 34.4 DID (Serbia) to 8.6 DID (Switzerland). The median consumption in 2021 was 19.3 DID (in 2020 it was 22.7 DID across 13 network members). The arithmetic and population-weighted mean totals of J01 consumption in 2021 were 20.4 and 20.3 DID, respectively (compared to 22.1 and 21.9 DID in 2020). 3 1 4 Route of administration in 2021 The extent of consumption of parenteral formulations in 2021 varied from 5% in Türkiye up to 25% in Tajikistan (Table 6). D ID Parenteral antibacterials Oral antibacterials 0 5 10 15 20 25 30 35 KG Z AL B TJ K SR B MN E BL R TU R RU S BI H AR M MK Dª GE O AZ E SW I a Community consumption. Fig. 1 Total consumption of J01 antibacterials by route of administration in 2020 12 ANTIMICROBIAL MEDICINES CONSUMPTION (AMC) NETWORK Table 6 Total consumption of J01 antibacterials by route of administration, 2021 Route of administration DID (% of totala) SRB MNE TUR BLR TJK BIH RUS MKDb AZE SWI WHO/AMCc Oral J01 30.4 (89) 27.6 (87) 26.8 (95) 18.5 (93) 14.7 (75) 17.5 (92) 13.8 (85) 15.3 (100) 9.5 (85) 7.8 (91) 18.2 (90) Parenteral J01 3.9 (11) 4.1 (13) 1.4 (5) 1.5 (7) 4.9 (25) 1.5 (8) 2.4 (15) – 1.7 (15) 0.8 (9) 2.1 (10) Totala 34.4 31.7 28.3 19.9 19.6 19.0 16.3 15.3 11.3 8.6 20.3 a Total amounts and percentages may vary slightly due to rounding. b Community consumption c WHO/AMC population-weighted mean for countries of the AMC Network. 3 1 5 Changes in total consumption of J01 antibacterials 2019–2021 Table 7 shows summary total consumption metrics for AMC Network countries in 2019, 2020 and 2021. Arithmetic mean and the WHO/AMC population-weighted consumption estimates were highest in 2020, reverting closer to 2019 levels in 2021. This is consistent with the pattern of increased consumption of antibacterial agents during 2020 and the early phases of the COVID-19 pandemic, and subsequent reductions as effective treatment regimens were identified, and agents promoted as potentially useful were shown to offer no benefits. Median consumption estimates were more stable over time, explained in part by variability in country-level consumption (Table 7). Table 7 Metrics of total consumption of J01 antibacterials for AMC Network countries, 2019–2021 Year (Number of countries) DID Median consumption Arithmetic mean consumption Population-weighted consumption 2019 (n=14) 19.6 19.6 21.2 2020 (n=13) 19.5 21.4 21.8 2021 (n=10) 19.3 20.4 20.3 D ID Parenteral antibacterials Oral antibacterials 0 5 10 15 20 25 30 35 SR B MN E TU R BL R TJ K BI H RU S MK Dª AZ E SW I a Community consumption Fig. 2 Total consumption of J01 antibacterials by route of administration in 2021 13 ANTIMICROBIAL MEDICINES CONSUMPTION ACROSS THE AMC NETWORK, 2020–2021 Consumption increased from 21.9 DID in 2019 to 34.3 DID in 2020 in Kyrgyzstan, and from 11.2 to 17.4 DID in Armenia, however no 2021 estimates were available for these two countries. Data from Belarus, the Russian Federation and Tajikistan showed increases in consumption from 2019 to 2020, then falling in 2021. Consumption in Serbia, however, increased in each of the years – from 26.6 DID in 2019, to 29.2 DID in 2020 and 34.4 DID in 2021. In Montenegro, total consumption was similar in 2019 and 2020 at 27.1 DID and 27.8 DID respectively, increasing to 31.7 DID in 2021. In Türkiye, total consumption fell substantially between 2019 and 2020 (33.2 DID to 25.8 DID) before increasing in 2021 to 28.3 DID (Table 8). Further investigation at the country level is needed to understand the reasons for the patterns seen and the possible contribution of the COVID-19 pandemic to the estimates. Table 8 Total consumption of J01 antibacterials 2019–2021 Year DID KGZ TJK SRB MNE BLR TUR RUS BIH ARM MKDa GEO AZE SWI UZB WHO/AMCb 2019 21.9 22.8 26.6 27.1 22.6 33.2 15.2 17.4 11.2 15.6 16.5 10.8 10.6 22.2 21.2 2020 34.3 30.0 29.2 27.8 25.9 25.8 19.5 19.2 17.4 14.5 14.3 10.8 9.0 – 21.8 2021 – 19.6 34.4 31.7 19.9 28.3 16.3 19.0 – 15.3 – 11.3 8.6 – 20.3 a Community consumption. b WHO/AMC population-weighted mean for countries of the AMC Network. 3 1 6 Pharmacological subgroups in 2020 Total consumption of antibacterials for systemic use (ATC class J01) in 2020 is examined by pharmacological subgroup (Fig. 3 and Table 9). There was considerable variation in the extent of consumption of the different pharmacological subgroups across the AMC Network. In 2020, consumption of beta-lactam penicillins (J01C) ranged from 20% of total J01 consumption in Azerbaijan to 42% of J01 consumption in Kyrgyzstan and Türkiye (Table 9). Cephalosporin (J01D) consumption varied from 10% of J01 consumption in Switzerland to 26% in Tajikistan. Quinolone (J01M) consumption varied from 9% in Montenegro to 22% in Azerbaijan. Consumption of macrolides, lincosamides and streptogramins (J01F) in 2020 ranged from 12% in Switzerland and Türkiye to 29% in Armenia, Belarus, Montenegro and Serbia. The AMC population- weighted consumption was 20%. 14 ANTIMICROBIAL MEDICINES CONSUMPTION (AMC) NETWORK Table 9 Total consumption of J01 antibacterials by pharmacological subgroup, 2020 Class of antibacterial agents DID (% of totala)  KGZ TJK SRB MNE BLR TUR RUS BIH MKDb GEO ARM AZE SWI WHO/AMC c Tetracyclines (J01A) 1.0 (3) 0.7 (2) 2.0 (7) 1.6 (6) 2.2 (9) 1.0 (4) 0.9 (4) 1.3 (7) < 0.1 (0) 0.7 (5) 1.9 (11) 1.0 (9) 1.4 (15) 1.0 (5) Amphenicols (J01B) 0.2 (0) 0.2 (1) – – 0.1 (0) – 0.1 (1) – – 0.8 (5) 0.1 (1) 0.1 (0) – 0.1 (0) Beta-lactam penicillins (J01C) 14.4 (42) 7.4 (25) 6.6 (23) 7.6 (27) 8.0 (31) 10.9 (42) 5.1 (26) 5.8 (30) 5.4 (37) 4.8 (33) 4.1 (23) 2.2 (20) 3.4 (38) 7.0 (32) Other beta- lactams (includes cephalosporins) (J01D) 7.6 (22) 7.8 (26) 5.9 (20) 6.3 (23) 3.6 (14) 6.3 (25) 2.4 (12) 3.2 (17) 3.6 (25) 1.9 (13) 1.9 (11) 1.6 (15) 0.9 (10) 3.9 (18) Sulfonamides and trimethoprim (J01E) 0.6 (2) 1.0 (3) 0.8 (3) 1.1 (4) 0.1 (0) 0.2 (1) 0.5 (3) 1.3 (7) 0.1 (1) 0.5 (4) 1.3 (7) 0.6 (6) 0.6 (6) 0.5 (2) Macrolides, lincosamides and streptogramins (J01F) 4.6 (14) 5.2 (17) 8.5 (29) 7.9 (29) 7.5 (29) 3.0 (12) 5.1 (26) 4.5 (23) 3.8 (26) 2.7 (19) 5.0 (29) 1.9 (18) 1.1 (12) 4.4 (20) Quinolone antibacterials (J01M) 4.0 (12) 4.9 (16) 4.6 (16) 2.5 (9) 2.8 (11) 2.8 (11) 3.9 (20) 2.5 (13) 1.5 (10) 2.0 (14) 2.4 (14) 2.4 (22) 1.0 (11) 3.4 (16) Other J01 antibacterials (J01G, J01R, J01X) 1.8 (5) 2.7 (9) 0.8 (3) 0.8 (3) 1.7 (7) 1.5 (6) 1.5 (8) 0.7 (4) – 0.9 (6) 0.7 (4) 1.0 (9) 0.7 (8) 1.5 (7) Total 34.3 30.0 29.2 27.8 25.9 25.8 19.5 19.2 14.5 14.3 11.2 10.8 9.0 21.8 a Total amounts and percentages may vary slightly due to rounding. b Community consumption. c WHO/AMC population-weighted mean for countries of the AMC Network. D ID Other J01 antibacterials (J01G, J01R, J01X) Quinolone antibacterials (J01M) Macrolides, lincosamides and streptogramins (J01F) Sulfonamides and trimethoprim (J01E) Other beta-lactams (includes cephalosporins) (J01D) Beta-lactams (J01C) Amphenicols (J01B) Tetracyclines (J01A)0 5 10 15 20 25 30 35 KG Z AL B TJ K SR B MN E BL R TU R RU S BI H AR M MK Dª GE O AZ E SW I a Community consumption. Fig. 3 Total consumption of J01 antibacterials by pharmacological subgroup, 2020 15 ANTIMICROBIAL MEDICINES CONSUMPTION ACROSS THE AMC NETWORK, 2020–2021 3 1 7 Pharmacological subgroups in 2021 In 2021, consumption of beta-lactam penicillins (J01C) ranged from 14% of total J01 consumption in Azerbaijan to 44% of J01 consumption in Türkiye (Fig. 4 and Table 10). The AMC Network population- weighted mean was 34%. Cephalosporin (J01D) consumption varied from 10% of J01 consumption in Belarus and Switzerland to 29% in Montenegro. Quinolone (J01M) consumption varied from 9% in Belarus to 24% in Azerbaijan. Consumption of macrolides, lincosamides and streptogramins (J01F) in 2021 ranged from 10% in Türkiye to 25% in Azerbaijan. D ID Other J01 antibacterials (J01G, J01R, J01X) Quinolone antibacterials (J01M) Macrolides, lincosamides and streptogramins (J01F) Sulfonamides and trimethoprim (J01E) Other beta-lactams (includes cephalosporins) (J01D) Beta-lactams (J01C) Amphenicols (J01B) Tetracyclines (J01A)0 5 10 15 20 25 30 35 SR B MN E TU R BL R TJ K BI H RU S MK Dª AZ E SW I a Community consumption. Fig. 4 Total consumption of J01 antibacterials by pharmacological subgroup, 2021 16 ANTIMICROBIAL MEDICINES CONSUMPTION (AMC) NETWORK Table 10 Total consumption of J01 antibacterials by pharmacological subgroup, 2021 Class of antibacterial agents DID (% of totala)  SRB MNE TUR BLR TJK BIH RUS MKDb AZE SWI WHO/AMCc Tetracyclines (J01A) 2.0 (6) 2.3 (7) 1.3 (5) 3.3 (17) 1.4 (7) 2.2 (12) 0.8 (5) < 0.1 (0) 1.6 (14) 1.3 (15) 1.2 (6) Amphenicols (J01B) – – – < 0.1 (0) 0.1 (1) – 0.1 (1) – 0.2 (2) – 0.1 (0) Beta-lactam penicillins (J01C) 7.7 (22) 7.6 (24) 12.4 (44) 7.4 (37) 5.8 (30) 5.8 (31) 4.4 (27) 5.8 (38) 1.6 (14) 3.3 (39) 7.0 (34) Other beta- lactams (includes cephalosporins) (J01D) 8.4 (24) 9.1 (29) 6.8 (24) 2.1 (10) 2.9 (15) 2.8 (15) 2.3 (14) 4.3 (28) 1.4 (12) 0.8 (10) 3.9 (19) Sulfonamides and trimethoprim (J01E) 1.0 (3) 1.0 (3) 0.3 (1) 0.1 (0) 0.4 (2) 1.1 (6) 0.4 (2) 0.1 (1) – 0.5 (6) 0.3 (2) Macrolides, lincosamides and streptogramins (J01F) 7.7 (22) 7.2 (23) 2.7 (10) 3.0 (15) 3.4 (17) 3.6 (19) 3.2 (20) 3.3 (22) 2.8 (25) 1.0 (11) 3.1 (15) Quinolone antibacterials (J01M) 6.7 (19) 3.3 (10) 3.0 (11) 1.8 (9) 3.8 (19) 2.5 (13) 3.6 (22) 1.6 (11) 2.7 (24) 0.9 (11) 3.3 (16) Other J01 antibacterials (J01G, J01R, J01X) 0.9 (3) 1.2 (4) 1.7 (6) 2.3 (12) 1.8 (9) 0.8 (4) 1.5 (9) – 0.9 (8) 0.7 (8) 1.5 (7) Total 34.4 31.7 28.3 19.9 19.6 19.0 16.3 15.3 11.3 8.6 20.3 a Total amounts and percentages may vary slightly due to rounding. b Community consumption. c WHO/AMC population-weighted mean for countries of the AMC Network. 3 1 8 Changes in consumption of pharmacological subgroups 2019–2021 Table 11 shows the AMC population-weighted estimates for consumption of pharmacological subgroups in 2019, 2020 and 2021. The most notable change was the increased relative consumption of the macrolides, lincosamides and streptogramins group (J01F), increasing from 14% of total J01 consumption in 2019 to 20% in 2020 (Table 11). Relative consumption fell towards 2019 levels in 2021 (15%). The increased consumption of J01F antibacterials is likely to relate in part to their use in diagnosed and presumed COVID-19 infections in 2020. The macrolides group includes azithromycin (J01FA10), which was promoted as a treatment for COVID-19 infection (Oliver & Hinks 2020; Touret et al. 2020). An AMC Network cross-sectional study of supplies of antimicrobials in community pharmacies conducted during the early phases of the pandemic showed that azithromycin was the most supplied agent across a range of clinical indications, not just presumed or confirmed COVID-19 infection (WHO Regional Office for Europe, 2022b). A United Kingdom-based randomized controlled trial (the PRINCIPLE trial) conducted in primary care settings failed to demonstrate that routine use of azithromycin reduced the time to recovery or the risk of hospitalization for people with suspected COVID-19 in the community (PRINCIPLE Trial Collaborative Group, 2021). This evidence was not published until March 2021. The findings of this trial and other published studies are likely to have contributed to the reduced consumption of azithromycin in 2021. 17 ANTIMICROBIAL MEDICINES CONSUMPTION ACROSS THE AMC NETWORK, 2020–2021 Table 11 Population-weighted consumption of pharmacological subgroups 2019–2021 Pharmacological subgroup AMC population-weighted consumption DID (% of totala) 2019 2020 2021 Tetracyclines (J01A) 1.2 (6) 1.0 (5) 1.2 (6) Amphenicols (J01B) 0.1 (0) 0.1 (0) 0.1 (0) Beta-lactam penicillins (J01C) 7.5 (35) 7.0 (32) 7.0 (34) Other beta-lactams (includes cephalosporins) (J01D) 4.4 (21) 3.9 (18) 3.9 (19) Sulfonamides and trimethoprim (J01E) 0.5 (2) 0.5 (2) 0.3 (2) Macrolides, lincosamides and streptogramins (J01F) 3.0 (14) 4.4 (20) 3.1 (15) Quinolone antibacterials (J01M) 3.1 (14) 3.4 (16) 3.3 (16) Other J01 antibacterials (J01G, J01R, J01X) 1.5 (7) 1.5 (7) 1.5 (7) Total 21.2 21.8 20.3 a Total amounts and percentages may vary slightly due to rounding. The summary population-weighted estimates of consumption of pharmacological subgroups do not illustrate the variability of changes at country level. Country-level consumption data for J01F antibacterials from 2019 to 2021 are shown in Table 12. Most countries showed increased relative consumption of J01F antibacterials from 2019 to 2020 and decreases in 2021. However, relative consumption was stable in Türkiye (12% of total J01 consumption in 2019 and 2020, falling to 10% in 2021) and Switzerland (13% in 2019, 12% in 2020, 11% in 2021). In North Macedonia, relative consumption of J01F antibacterials fell in 2020 and then increased in 2021 back to 2019 levels. Consumption of J01F antibacterials continued to increase in Azerbaijan, at 10% relative consumption in 2019, 18% in 2020 and 25% in 2021. Table 12 Consumption of J01F antibacterials 2019–2021 Year DID (% of totala)  ARM AZE BIH BLR GEO KGZ  MKDb MNE RUS SRB SWI TJK TUR UZB WHO/AMCc 2019 2.1 (19) 1.0 (10) 2.4 (14) 3.1 (14) 2.4 (15) 1.8 (8) 3.4 (22) 5.1 (19) 2.7 (18) 5.6 (21) 1.4 (13) 1.4 (6) 4.1 (12) 3.0 (13) 3.0 (14) 2020 3.8 (26) 1.9 (18) 4.5 (23) 7.5 (29) 5.0 (29) 4.6 (14) 2.7 (19) 7.9 (29) 5.1 (26) 8.5 (29) 1.1 (12) 5.2 (17) 3.0 (12) – 4.4 (20) 2021 – 2.8 (25) 3.6 (19) 3.0 (15) – – 3.3 (22) 7.2 (23) 3.2 (20) 7.7 (22) 1.0 (11) 3.4 (17) 2.7 (10) – 3.1 (15) a Total amounts and percentages may vary slightly due to rounding. b Community consumption. c WHO/AMC population-weighted mean for countries of the AMC Network. 18 ANTIMICROBIAL MEDICINES CONSUMPTION (AMC) NETWORK 3 1 9 Trends, 2014–2021 Table 13 shows the trends in total consumption of antibacterials for systemic use (ATC J01) for the years 2014–2021. The CAGR of total antibiotic consumption was calculated for each participating country. This reflects the average annual change as a proportion (%) of the consumption in the starting year. The CAGR was estimated for countries that had at least five years of data available. Linear regression was used for presenting trends in consumption and evaluated using ANOVA tests. P values ≤ 0.05 were considered statistically significant. Countries are grouped according to comparability of data sets. Ten countries – Azerbaijan, Belarus, Bosnia and Herzegovina, Montenegro, North Macedonia, the Russian Federation, Serbia, Switzerland, Tajikistan and Türkiye – had consumption estimates for all years 2014–2021. Three of these countries showed statistically significant increases in consumption of J01 antibacterials over the eight years of data collection – Azerbaijan (CAGR +8.4%), Bosnia and Herzegovina (+3.1%) and the Russian Federation (+2.8%). Three countries showed statistically significant reductions in consumption over time – North Macedonia (−0.9%), Switzerland (−3.6%) and Türkiye (−2.9%). Table 13 Trends in consumption of J01 antibacterials, 2014–2021 Country Total consumption of J01 antibacterials in DID CAGRa Trend line Trendb 2014 2015 2016 2017 2018 2019 2020 2021 – KAZ – 17.4 15.7 14.3 15.1 – – – – – – MDA 16.7 12.9 16.7 17.1 14.2 – – – −4.1% – UKR 9.5 12.1 8.3 10.7 11.7 – – – 5.3% – ALB 19.6 16.3 16.5 18.7 19.0 17.2 – – −2.6% – UZB – – 25.1 16.3 18.2 22.2 – – – – – ARM 12.7 9.4 9.4 12.0 12.1 11.2 17.4 – 5.3% – GEO 17.9 24.2 22.5 25.1 20.8 16.5 14.3 – −3.7% – KGZ 33.1 16.7 21.3 16.9 11.2 21.9 34.3 – 0.6% – AZE 6.4 7.4 9.5 7.8 8.9 10.8 10.8 11.3 8.4% ↑ BIH 15.3 16.3 18.0 17.4 19.3 17.4 19.2 19.0 3.1% ↑ BLR 18.3 17.1 16.9 20.0 18.9 22.6 25.9 19.9 1.3% – MKDc 16.3 16.7 17.0 16.9 16.6 15.6 14.5 15.3 −0.9% ↓ MNE 26.7 29.0 28.9 27.1 27.0 27.1 27.8 31.7 2.5% – RUS 13.4 14.1 14.9 15.1 14.7 15.2 19.5 16.3 2.8% ↑ SRB 25.3 31.0 26.2 21.3 22.7 26.6 29.2 34.4 4.5% – SWI 11.1 11.1 10.9 10.5 10.7 10.6 9.0 8.6 −3.6% ↓ TJK 31.0 21.7 20.9 16.3 19.0 22.8 30.0 19.6 −6.3% – TUR 34.7 35.5 35.3 31.0 30.9 33.2 25.8 28.3 −2.9% ↓ ↑↓ indicates statistically significant change. a The CAGR was only calculated where there were five years of data available for the country. b Linear regression analysis. C Community consumption. 19 ANTIMICROBIAL MEDICINES CONSUMPTION ACROSS THE AMC NETWORK, 2020–2021 3 2 Relative consumption of AWaRe groups of antibiotics Analyses based on the WHO AWaRe groups of antibiotics can support antimicrobial stewardship efforts and focus attention on prescribing practices that should be reviewed further. 3 2 1 AWaRe 2020 The relative consumption of Access, Watch and Reserve group antibiotics in 2020 is shown in Fig. 5 and is summarized in Table 14. Consumption of Access agents represented between 41% (North Macedonia, Russian Federation, Tajikistan) and 63% (Switzerland) of total antibacterial consumption in 2020 (Table 14). In 5 of 13 countries (36%), Access agents comprised ≥ 50% of total antibacterial consumption. This compares to 12 of 14 countries (86%) meeting this measure in 2019. Watch group agents represented between 37% (Switzerland) and 58% (Tajikistan) of total consumption. Consumption of Reserve agents remained low in all 13 countries. Unclassified agents constituted 3% of consumption in North Macedonia and 2% of consumption in Georgia, Kyrgyzstan and the Russian Federation. The 2020 population-weighted estimates across the AMC Network were: Access agents 46%, Watch agents 52%, Reserve agents 0.2% and unclassified agents 1.5%. MN E SR B AR M RU S MK D Unclassified Reserve Watch Access P ro po rt io n of c on su m pt io n (% ) 0 20 40 60 80 100 SW I KG Z BI H TU R GE O MN E AR M BL R AZ E SR B RU S MK D b TJ K a Total consumption of antibiotics for this calculation includes J01 antibacterials, neomycin (A07AA01), streptomycin (A07AA04), polymyxin B (A07AA05), kanamycin (A07AA08), vancomycin (A07AA09), colistin (A07AA10), rifamixin (A07AA11), fidaxomicin (A07AA12), rifamycin oral (A07AA13), rifampicin (J04AB02), rifamycin intravenous (J04AB03), rifabutin (J04AB04), metronidazole (P01AB01), tinidazole (P01AB02), ornidazole (P01AB03) and secnidazole (P01AB07). b Community consumption. Fig. 5 Relative consumption of antibacterials by WHO AWaRe classification as a proportion of total consumptiona, 2020 20 ANTIMICROBIAL MEDICINES CONSUMPTION (AMC) NETWORK Table 14 Relative consumption of Access, Watch and Reserve classification antibacterials, 2020 Group of antibacterial agents Consumption according to 2021 WHO AWaRe classificationa SWI KGZ BIH TUR GEO MNE ARM BLR AZE SRB RUS MKDb TJK WHO/AMCc Access 5.9 (63%) 19.1 (54%) 10.3 (53%) 14.3 (53%) 7.7 (53%) 13.7 (48%) 8.4 (47%) 12.5 (47%) 5.4 (46%) 13.4 (45%) 8.3 (41%) 5.9 (41%) 12.3 (41%) 10.5 (46%) Watch 3.4 (37%) 15.8 (44%) 9.1 (47%) 12.3 (46%) 6.7 (46%) 14.5 (51%) 9.4 (52%) 13.8 (52%) 6.2 (53%) 16.4 (55%) 11.6 (57%) 8.2 (56%) 17.5 (58%) 11.7 (52%) Reserve < 0.1 (0%) < 0.1 (0%) < 0.1 (0%) 0.1 (0%) < 0.1 (0%) < 0.1 (0%) < 0.1 (0%) 0.1 (0%) – < 0.1 (0%) < 0.1 (0%) – < 0.1 (0%) 0.1 (0%) Unclassified < 0.1 (0%) 0.7 (2%) < 0.1 (0%) 0.4 (1%) 0.2 (2%) 0.3 (1%) 0.1 (0%) 0.2 (1%) 0.1 (1%) 0.1 (0%) 0.4 (2%) 0.5 (3%) 0.5 (1%) 0.3 (2%) Total 9.3 35.5 19.5 27.0 14.6 28.5 17.9 26.6 11.7 29.9 20.3 14.6 30.3 22.6 a Total consumption of antibiotics for this calculation includes: J01 antibacterials, neomycin (A07AA01), streptomycin (A07AA04), polymyxin B (A07AA05), kanamycin (A07AA08), vancomycin (A07AA09), colistin (A07AA10), rifamixin (A07AA11), fidaxomicin (A07AA12), rifamycin oral (A07AA13), rifampicin (J04AB02), rifamycin intravenous (J04AB03), rifabutin (J04AB04), metronidazole (P01AB01), tinidazole (P01AB02), ornidazole (P01AB03) and secnidazole (P01AB07). b Community consumption. c Total amounts and percentages may vary slightly due to rounding. 3 2 2 AWaRe 2021 The relative consumption of Access, Watch and Reserve group antibiotics in 2021 is shown in Fig. 6 and is summarized in Table 15. Consumption of Access agents represented between 40% (Azerbaijan) and 66% (Belarus) of total antibacterial consumption in 2021 (Table 15). In 4 of 10 countries (40%), Access agents comprised ≥ 50% of total antibacterial consumption. By comparison, Watch group agents represented between 33% (Belarus) and 59% (Azerbaijan) of total consumption. The 2021 population-weighted estimates across the AMC Network were: Access agents 50%, Watch agents 49%, Reserve agents 0.3% and unclassified agents 1.4%. Unclassified Reserve Watch Access P ro po rt io n of c on su m pt io n (% ) 0 20 40 60 80 100 BL R SW I BI H TU R TJ K MN E RU S MK D b SR B AZ E a Total consumption of antibiotics for this calculation includes J01 antibacterials, neomycin (A07AA01), streptomycin (A07AA04), polymyxin B (A07AA05), kanamycin (A07AA08), vancomycin (A07AA09), colistin (A07AA10), rifamixin (A07AA11), fidaxomicin (A07AA12), rifamycin oral (A07AA13), rifampicin (J04AB02), rifamycin intravenous (J04AB03), rifabutin (J04AB04), metronidazole (P01AB01), tinidazole (P01AB02), ornidazole (P01AB03) and secnidazole (P01AB07). b Community consumption. Fig. 6 Relative consumption of antibacterials by WHO AWaRe classification as a proportion of total consumptiona, 2021 21 ANTIMICROBIAL MEDICINES CONSUMPTION ACROSS THE AMC NETWORK, 2020–2021 Table 15 Relative consumption of AWaRe classification antibacterials, 2021 Group of antibacterial agents Consumption according to 2021 WHO AWaRe classificationa BLR SWI BIH TUR TJK MNE RUS MKDb SRB AZE WHO/AMCc Access 13.3 (66%) 5.7 (65%) 11.2 (58%) 16.6 (56%) 9.8 (49%) 14.9 (46%) 7.3 (43%) 6.5 (42%) 14.7 (42%) 4.7 (40%) 10.6 (50%) Watch 6.8 (33%) 3.1 (35%) 8.2 (42%) 12.7 (43%) 9.5 (47%) 17.6 (54%) 9.4 (55%) 8.5 (55%) 20.5 (58%) 7.0 (59%) 10.4 (49%) Reserve 0.1 (0%) < 0.1 (0%) < 0.1 (0%) 0.1 (0%) 0.2 (1%) < 0.1 (0%) 0.1 (0%) – 0.1 (0%) – 0.1 (0%) Unclassified 0.1 (0%) < 0.1 (0%) < 0.1 (0%) 0.3 (1%) 0.5 (2%) 0.1 (0%) 0.3 (2%) 0.4 (3%) 0.1 (0%) 0.1 (1%) 0.3 (1%) Total 20.2 8.9 19.4 29.7 20.0 32.6 17.0 15.4 35.3 11.7 21.4 a Total consumption of antibiotics for this calculation includes: J01 antibacterials, neomycin (A07AA01), streptomycin (A07AA04), polymyxin B (A07AA05), kanamycin (A07AA08), vancomycin (A07AA09), colistin (A07AA10), rifamixin (A07AA11), fidaxomicin (A07AA12), rifamycin oral (A07AA13), rifampicin (J04AB02), rifamycin intravenous (J04AB03), rifabutin (J04AB04), metronidazole (P01AB01), tinidazole (P01AB02), ornidazole (P01AB03) and secnidazole (P01AB07). b Community consumption. c Total amounts and percentages may vary slightly due to rounding. 3 2 3 Changes in AWaRe 2019–2021 WHO/AMC Network population-weighted estimates of the relative consumption of Access, Watch and Reserve classification antibacterials from 2019–2021 are shown in Table 16. Across AMC Network countries, the relative consumption of Access agents was 50% in 2019, 46% in 2020 and 50% in 2021 (Table 16). Watch group antibiotics constituted 47%, 52% and 49% of total consumption in 2019, 2020 and 2021 respectively. Consumption of Reserve agents and unclassified antibacterials was low in all three years. Table 16 Relative consumption of AWaRe classification antibacterials, 2019–2021 Group of antibacterial agents Consumption according to 2021 WHO AWaRe classificationa WHO/AMC population-weighted estimates DID (% of totalb) 2019 2020 2021 Access 11.2 (50%) 10.5 (46%) 10.6 (50%) Watch 10.3 (47%) 11.7 (52%) 10.4 (49%) Reserve < 0.1 (0%) 0.1 (0%) 0.1 (0%) Unclassified 0.6 (3%) 0.3 (2%) 0.3 (1%) Total 22.1 22.6 21.4 a Total consumption of antibiotics for this calculation includes: J01 antibacterials, neomycin (A07AA01), streptomycin (A07AA04), polymyxin B (A07AA05), kanamycin (A07AA08), vancomycin (A07AA09), colistin (A07AA10), rifamixin (A07AA11), fidaxomicin (A07AA12), rifamycin oral (A07AA13), rifampicin (J04AB02), rifamycin intravenous (J04AB03), rifabutin (J04AB04), metronidazole (P01AB01), tinidazole (P01AB02), ornidazole (P01AB03) and secnidazole (P01AB07). b Total amounts and percentages may vary slightly due to rounding. 3 2 4 WHO global monitoring indicator In 2019, WHO proposed a global monitoring indicator that by 2023, 60% of all antibiotics consumed should come from Access, the group of antibiotics at lowest risk of resistance (WHO, 2018, 2019). Trends in the relative consumption of Access agents between 2014 and 2019 are shown in Table 17. 22 ANTIMICROBIAL MEDICINES CONSUMPTION (AMC) NETWORK Most countries showed patterns like the AMC Network averages, namely decreases in relative consumption of Access agents from 2019 to 2020 and increases in 2021. Russian Federation data indicate a reduction in relative consumption of Access agents from 50% in 2019, to 41% in 2020 and 43% in 2021. Five countries, Azerbaijan, Belarus, Bosnia and Herzegovina, Montenegro and Switzerland, would have met the WHO target of at least 60% of total consumption being Access agents in 2019 (Table 17). Only one country, Switzerland, met the WHO target in 2020. This is consistent with the increased consumption of Watch agents in most AMC Network countries in 2020. Two countries, Belarus and Switzerland met the global monitoring target in 2021. No country in the AMC Network met the global monitoring indicator in each of the eight years examined (2014–2021). Table 17 Countries achieving the target of 60% of total consumption being Access agents, 2014–2021 Countrya  Access agents as proportion (%) of total consumptionb 2014 2015 2016 2017 2018 2019 2020 2021 ALB 61 48 51 44 40 38 – – ARM 67 68 58 66 63 57 47 – AZE 58 61 50 56 62 71 46 40 BIH 69 69 70 68 66 63 53 58 BLR 57 60 56 62 61 67 47 66 GEO 32 46 60 64 43 54 53 – KAZ – 63 60 57 53 – – – KGZ – 72 56 50 34 54 54 – MDA 49 56 47 49 51 – – – MKDc 53 49 50 48 47 46 41 42 MNE 61 56 58 59 57 60 48 46 RUS 51 51 51 51 50 50 41 43 SRB 68 65 63 60 51 58 45 42 SWI 56 57 59 59 61 62 63 65 TJK 65 58 62 46 43 55 41 49 TUR 45 45 47 48 51 51 53 56 UKR 46 37 51 42 40 – – – UZB – – 31 42 30 35 – – Note: Green cells indicate that a country has met the 60% target. a Country estimates are rounded up. b Total consumption of antibiotics for this calculation includes: J01 antibacterials, neomycin (A07AA01), streptomycin (A07AA04), polymyxin B (A07AA05), kanamycin (A07AA08), vancomycin (A07AA09), colistin (A07AA10), rifamixin (A07AA11), fidaxomicin (A07AA12), rifamycin oral (A07AA13), rifampicin (J04AB02), rifamycin intravenous (J04AB03), rifabutin (J04AB04), metronidazole (P01AB01), tinidazole (P01AB02), ornidazole (P01AB03) and secnidazole (P01AB07). C Community consumption. 3 3 DU75% The DU75% represents the antibacterial substances accounting for 75% of consumption measured in DDD (Zarb et al., 2011). The DU75% is calculated for oral and parenteral formulations separately. Results are shown as the ranking of consumption at substance level (ATC 5th group level). In addition to reporting the numbers of antibacterial agents in the DU75% segment, the agents are categorized according to the AWaRe classification. This facilitates identification of restricted and special use antibacterials that may be widely consumed and be potential targets for stewardship activities. 23 ANTIMICROBIAL MEDICINES CONSUMPTION ACROSS THE AMC NETWORK, 2020–2021 3 3 1 DU75% 2020 Table 18 (oral agents) and Table 19 (parenteral agents) show the ranking of consumption of antibacterial agents that comprised the DU75% in 2020. The number of agents constituting the DU75% by oral substance ranged from 5 to 9 across the AMC Network countries (Table 18). There were nine agents in the population-weighted DU75% for the AMC Network. Azithromycin (J01FA10), a macrolide, was included in the DU75% for 12 of the 13 AMC Network countries and was ranked first most consumed antibiotic in six countries and second in a further five countries. It ranked first in the population-weighted DU75%. Oral amoxicillin and beta-lactamase inhibitor (ATC code J01CR02) was included in the DU75% in 12 of 13 AMC Network countries, ranked first for consumption in four of those countries and second in the population-weighted DU75%. Amoxicillin (J01CA04) ranked third in the population-weighted DU75%, appeared in the DU75% for 12 countries, and was ranked the most consumed oral antibiotic in two countries. Ciprofloxacin (J01MA02), a fluoroquinolone, was included in the DU75% for 9 of the 13 AMC Network countries and was ranked third to fifth most consumed antibiotic in those countries. It ranked fourth in the population-weighted DU75%. Two to five Watch agents appeared in the DU75% for each of the AMC Network countries and there were six Watch agents in the population-weighted Network estimate. There were no unclassified oral agents included in the DU75% for any AMC Network country. The most notable change between 2019 and 2020 was the increased relative consumption of azithromycin – rising from fourth to most consumed oral antibiotic across the AMC Network in 2020. In 2020, the number of agents constituting the DU75% by parenteral substance ranged from 3 to 10 across the AMC Network countries (Table 19). There were seven agents in the population-weighted DU75%. The Watch agent ceftriaxone (J01DD04) was ranked number one in nine countries, ranked second in two countries and third in one country. This analysis excludes North Macedonia as only consumption data for oral agents is reported. 24 ANTIMICROBIAL MEDICINES CONSUMPTION (AMC) NETWORK Ta bl e 18 R an ki ng o f c on su m pt io n of a nt ib ac te ri al s at s ub st an ce le ve l ( AT C 5 th le ve l) th at c om pr is e th e D U 75 % (o ra l u se ), 20 20 a A ge nt (A TC )b R an ki ng o f c on su m pt io n of a nt ib ac te ri al a ge nt s th at c om pr is ed th e D U 75 % N um be r of co un tr ie sc W H O /A M C d A R M A ZE B IH B LR G EO K G Z M K D M N E R U S S R B S W I TJ K TU R A m ox ic ill in (J 01 CA 04 ) 2 3 3 3 7 1 2 2 2 3 1 8 12 3 A m ox ic ill in a nd b et a- la ct am as e in hi bi to r (J 01 CR 02 ) 4 6 2 2 1 7 1 6 3 3 1 1 12 2 D ox yc yc lin e (J 01 A A 02 ) 3 6 4 6 7 6 2 6 8 5 S ul fa m et ho xa zo le a nd tr im et ho pr im (J 01 EE 01 ) 5 7 5 5 4 5 9 N itr of ur an to in (J 01 XE 01 ) 8 8 6 9 4 Ce fa le xi n (J 01 D B 01 ) 8 5 5 3 M et ro ni da zo le (P 01 A B 01 ) 4 6 2 Te tr ac yc lin e (J 01 A A 07 ) 5 1 Ch lo ra m ph en ic ol (J 01 B A 01 ) 4 1 A zi th ro m yc in (J 01 FA 10 ) 1 2 1 1 2 2 2 1 1 1 8 2 12 1 Ci pr ofl ox ac in (J 01 M A 02 ) 4 5 3 5 4 5 4 3 4 9 4 Le vo fl ox ac in (J 01 M A 12 ) 6 1 6 3 4 4 7 7 6 Ce fix im e (J 01 D D 08 ) 5 3 3 8 4 5 6 8 Cl ar ith ro m yc in (J 01 FA 09 ) 5 4 6 7 3 5 7 Ce fu ro xi m e (J 01 D C0 2) 7 8 6 2 4 Ce fa cl or (J 01 D C0 4) 7 1 Er yt hr om yc in (J 01 FA 01 ) 5 1 a T he a nt ib ac te ri al s ra nk ed in th is ta bl e ar e gr ou pe d by A cc es s ag en ts (g re en ) a nd W at ch a ge nt s (y el lo w ). b A ge nt s in cl ud ed in th is a na ly si s: J 01 a nt ib ac te ri al s, n eo m yc in (A 07 A A 01 ), st re pt om yc in (A 07 A A 04 ), po ly m yx in B (A 07 A A 05 ), ka na m yc in (A 07 A A 08 ), va nc om yc in (A 07 A A 09 ), co lis tin (A 07 A A 10 ), ri fa m ix in (A 07 A A 11 ), fid ax om ic in (A 07 A A 12 ), ri fa m yc in o ra l ( A 07 A A 13 ), ri fa m pi ci n (J 04 A B 02 ), ri fa m yc in in tr av en ou s (J 04 A B 03 ), ri fa bu tin (J 04 A B 04 ), m et ro ni da zo le (P 01 A B 01 ), tin id az ol e (P 01 A B 02 ), or ni da zo le (P 01 A B 03 ) a nd s ec ni da zo le (P 01 A B 07 ). c N um be rs o f c ou nt ri es th at h av e th is a ge nt in th e D U 75 % . d W H O /A M C po pu la tio n- w ei gh te d m ea n fo r co un tr ie s of th e A M C N et w or k. 25 ANTIMICROBIAL MEDICINES CONSUMPTION ACROSS THE AMC NETWORK, 2020–2021 Ta bl e 19 R an ki ng o f c on su m pt io n of a nt ib ac te ri al s at s ub st an ce le ve l ( AT C 5 th le ve l) th at c om pr is e th e D U 75 % (p ar en te ra l u se ), 20 20 a A ge nt (A TC )b R an ki ng o f c on su m pt io n of a nt ib ac te ri al a ge nt s th at c om pr is ed th e D U 75 % N um be r of co un tr ie sc W H O /A M C d A R M A ZE B IH B LR G EO K G Z M N E R U S S R B S W I TJ K TU R Ce fa zo lin (J 01 D B 04 ) 3 4 4 5 2 5 6 G en ta m ic in (J 01 G B 03 ) 2 2 3 10 4 7 M et ro ni da zo le (J 01 XD 01 ) 4 4 2 4 4 5 A m pi ci lli n (J 01 CA 01 ) 1 2 2 2 A m pi ci lli n an d be ta -l ac ta m as e in hi bi to r (J 01 CR 01 ) 6 9 2 A m ox ic ill in a nd b et a- la ct am as e in hi bi to r (J 01 CR 02 ) 6 1 2 A m ik ac in (J 01 G B 06 ) 3 5 2 Fl uc lo xa ci lli n (J 01 CF 05 ) 6 1 Ce ft ri ax on e (J 01 D D 04 ) 1 1 1 1 1 3 1 1 2 2 1 1 12 1 Le vo fl ox ac in (J 01 M A 12 ) 3 2 2 5 2 1 3 6 8 3 M er op en em (J 01 D H 02 ) 5 3 5 3 4 Ce fo ta xi m e (J 01 D D 01 ) 3 2 3 3 4 P ip er ac ill in a nd b et a- la ct am as e in hi bi to r (J 01 CR 05 ) 4 5 2 M ox ifl ox ac in (J 01 M A 14 ) 2 7 2 Ce fu ro xi m e (J 01 D C0 2) 3 1 Ce fe pi m e (J 01 D E0 1) 4 1 K an am yc in (J 01 G B 04 ) 3 1 Va nc om yc in (J 01 XA 01 ) 4 1 Te ic op la ni n (J 01 XA 02 ) 8 1 R ifa m yc in (J 04 A B 03 ) 4 1 a T he a nt ib ac te ri al s ra nk ed in th is ta bl e ar e gr ou pe d by A cc es s ag en ts (g re en ) a nd W at ch a ge nt s (y el lo w ). b A ge nt s in cl ud ed in th is a na ly si s: J 01 a nt ib ac te ri al s, n eo m yc in (A 07 A A 01 ), st re pt om yc in (A 07 A A 04 ), po ly m yx in B (A 07 A A 05 ), ka na m yc in (A 07 A A 08 ), va nc om yc in (A 07 A A 09 ), co lis tin (A 07 A A 10 ), ri fa m ix in (A 07 A A 11 ), fid ax om ic in (A 07 A A 12 ), ri fa m yc in o ra l ( A 07 A A 13 ), ri fa m pi ci n (J 04 A B 02 ), ri fa m yc in in tr av en ou s (J 04 A B 03 ), ri fa bu tin (J 04 A B 04 ), m et ro ni da zo le (P 01 A B 01 ), tin id az ol e (P 01 A B 02 ), or ni da zo le (P 01 A B 03 ) a nd s ec ni da zo le (P 01 A B 07 ). c N um be rs o f c ou nt ri es th at h av e th is a ge nt in th e D U 75 % . d W H O /A M C po pu la tio n- w ei gh te d m ea n fo r co un tr ie s of th e A M C N et w or k. 26 ANTIMICROBIAL MEDICINES CONSUMPTION (AMC) NETWORK 3 3 2 DU75% 2021 Table 20 (oral agents) and Table 21 (parenteral agents) show the ranking of consumption of antibacterial agents that comprised the DU75% in 2021. The number of agents constituting the DU75% by oral substance ranged from 6 to 8 across the AMC Network countries, with nine agents in the population-weighted DU75% (Table 20). Oral doxycycline (J01AA02), amoxicillin (J01CA04), amoxicillin and beta-lactamase inhibitor (J01CR02) and azithromycin (J01FA10) were included in the DU75% in 9 of 10 AMC Network countries. Amoxicillin and beta-lactamase inhibitor ranked first for consumption in six of those countries and first in the population-weighted DU75%. Azithromycin was ranked second in the population-weighted DU75%. Two to five Watch agents appeared in the DU75% for each of the AMC Network countries and there were six Watch agents in the population-weighted Network estimate. In 2021, the number of agents constituting the DU75% by parenteral substance ranged from 3 to 10 across the AMC Network countries (Table 21). There were four Access agents and four Watch agents in the population-weighted DU75%. The Watch agent ceftriaxone (J01DD04) was ranked number one in seven countries and ranked second in a further two countries. 27 ANTIMICROBIAL MEDICINES CONSUMPTION ACROSS THE AMC NETWORK, 2020–2021 Ta bl e 20 R an ki ng o f c on su m pt io n of a nt ib ac te ri al s at s ub st an ce le ve l ( AT C 5 th le ve l) th at c om pr is e th e D U 75 % (o ra l u se ), 20 21 a A ge nt (A TC )b R an ki ng o f c on su m pt io n of a nt ib ac te ri al a ge nt s th at c om pr is ed th e D U 75 % N um be r of co un tr ie sc W H O /A M C d A ZE B IH B LR M K D M N E R U S S R B S W I TJ K TU R D ox yc yc lin e (J 01 A A 02 ) 4 4 2 6 7 6 2 4 5 9 7 A m ox ic ill in (J 01 CA 04 ) 6 3 3 6 1 3 3 3 1 9 3 A m ox ic ill in a nd b et a- la ct am as e in hi bi to r (J 01 CR 02 ) 3 1 1 1 5 1 4 1 1 9 1 N itr of ur an to in (J 01 XE 01 ) 5 8 6 7 4 S ul fa m et ho xa zo le a nd tr im et ho pr im (J 01 EE 01 ) 6 5 2 Te tr ac yc lin e (J 01 A A 07 ) 5 1 A m pi ci lli n (J 01 CA 01 ) 5 1 Ce fa le xi n (J 01 D B 01 ) 7 1 M et ro ni da zo le (P 01 A B 01 ) 7 1 A zi th ro m yc in (J 01 FA 10 ) 1 2 4 5 2 2 1 7 2 9 2 Ci pr ofl ox ac in (J 01 M A 02 ) 5 4 4 5 8 4 3 3 8 4 Ce fix im e (J 01 D D 08 ) 2 3 2 6 4 9 Cl ar ith ro m yc in (J 01 FA 09 ) 7 3 6 4 4 6 Le vo fl ox ac in (J 01 M A 12 ) 2 4 5 6 4 5 Ce fu ro xi m e (J 01 D C0 2) 6 2 2 8 Ce fa cl or (J 01 D C0 4) 8 1 a T he a nt ib ac te ri al s ra nk ed in th is ta bl e ar e gr ou pe d by A cc es s ag en ts (g re en ) a nd W at ch a ge nt s (y el lo w ). b A ge nt s in cl ud ed in th is a na ly si s: J 01 a nt ib ac te ri al s, n eo m yc in (A 07 A A 01 ), st re pt om yc in (A 07 A A 04 ), po ly m yx in B (A 07 A A 05 ), ka na m yc in (A 07 A A 08 ), va nc om yc in (A 07 A A 09 ), co lis tin (A 07 A A 10 ), ri fa m ix in (A 07 A A 11 ), fid ax om ic in (A 07 A A 12 ), ri fa m yc in o ra l ( A 07 A A 13 ), ri fa m pi ci n (J 04 A B 02 ), ri fa m yc in in tr av en ou s (J 04 A B 03 ), ri fa bu tin (J 04 A B 04 ), m et ro ni da zo le (P 01 A B 01 ), tin id az ol e (P 01 A B 02 ), or ni da zo le (P 01 A B 03 ) a nd s ec ni da zo le (P 01 A B 07 ). c N um be rs o f c ou nt ri es th at h av e th is a ge nt in th e D U 75 % . d W H O /A M C po pu la tio n- w ei gh te d m ea n fo r co un tr ie s of th e A M C N et w or k. 28 ANTIMICROBIAL MEDICINES CONSUMPTION (AMC) NETWORK Ta bl e 21 R an ki ng o f c on su m pt io n of a nt ib ac te ri al s at s ub st an ce le ve l ( AT C 5 th le ve l) th at c om pr is e th e D U 75 % (p ar en te ra l u se ), 20 21 a A ge nt (A TC )b R an ki ng o f c on su m pt io n of a nt ib ac te ri al a ge nt s th at c om pr is ed th e D U 75 % N um be r of co un tr ie sc W H O /A M C d A ZE B IH B LR M N E R U S S R B S W I TJ K TU R Ce fa zo lin (J 01 D B 04 ) 2 5 4 6 2 5 3 M et ro ni da zo le (J 01 XD 01 ) 3 5 2 5 4 5 5 G en ta m ic in (J 01 G B 03 ) 3 2 3 10 4 8 A m ik ac in (J 01 G B 06 ) 4 3 6 3 7 A m pi ci lli n (J 01 CA 01 ) 2 1 Fl uc lo xa ci lli n (J 01 CF 05 ) 5 1 A m pi ci lli n an d be ta -l ac ta m as e in hi bi to r (J 01 CR 01 ) 9 1 A m ox ic ill in a nd b et a- la ct am as e in hi bi to r (J 01 CR 02 ) 1 1 Ce ft ri ax on e (J 01 D D 04 ) 1 1 1 1 1 2 2 1 1 9 1 Le vo fl ox ac in (J 01 M A 12 ) 2 4 2 1 3 8 6 2 Ce fo ta xi m e (J 01 D D 01 ) 3 3 2 6 M er op en em (J 01 D H 02 ) 6 3 2 4 P ip er ac ill in a nd b et a- la ct am as e in hi bi to r (J 01 CR 05 ) 4 5 2 Ce fu ro xi m e (J 01 D C0 2) 3 1 M ox ifl ox ac in (J 01 M A 14 ) 6 1 Te ic op la ni n (J 01 XA 02 ) 7 1 R ifa m yc in (J 04 A B 03 ) 4 1 Ce ft ri ax on e an d be ta -l ac ta m as e in hi bi to r (J 01 D D 63 ) 5 1 a T he a nt ib ac te ri al s ra nk ed in th is ta bl e ar e gr ou pe d by A cc es s ag en ts (g re en ) a nd W at ch a ge nt s (y el lo w ). b A ge nt s in cl ud ed in th is a na ly si s: J 01 a nt ib ac te ri al s, n eo m yc in (A 07 A A 01 ), st re pt om yc in (A 07 A A 04 ), po ly m yx in B (A 07 A A 05 ), ka na m yc in (A 07 A A 08 ), va nc om yc in (A 07 A A 09 ), co lis tin (A 07 A A 10 ), ri fa m ix in (A 07 A A 11 ), fid ax om ic in (A 07 A A 12 ), ri fa m yc in o ra l ( A 07 A A 13 ), ri fa m pi ci n (J 04 A B 02 ), ri fa m yc in in tr av en ou s (J 04 A B 03 ), ri fa bu tin (J 04 A B 04 ), m et ro ni da zo le (P 01 A B 01 ), tin id az ol e (P 01 A B 02 ), or ni da zo le (P 01 A B 03 ) a nd s ec ni da zo le (P 01 A B 07 ). c N um be rs o f c ou nt ri es th at h av e th is a ge nt in th e D U 75 % . d W H O /A M C po pu la tio n- w ei gh te d m ea n fo r co un tr ie s of th e A M C N et w or k. 29 ANTIMICROBIAL MEDICINES CONSUMPTION ACROSS THE AMC NETWORK, 2020–2021 3 4 GLASS-IT platform WHO launched GLASS in 2015 to foster harmonized antimicrobial resistance and use surveillance in all countries and thus inform strategies to contain AMR. GLASS initially focused on surveillance data on human priority bacterial pathogens considered the most significant threat globally. The scope of GLASS has since widened and now incorporates surveillance data on antimicrobial medicines consumption (GLASS-AMC). WHO has invited AMC Network members to participate in GLASS-AMC. Participation changes the processes for reporting and approval of AMC data. The GLASS-IT platform allows Member States to view their own current and historical AMC data on dedicated country pages. In addition to the metrics presented in this report, GLASS-AMC reports will also report on: • Consumption of penicillins (J01CA, J01CE, J01CF and J01CR) (quantity of antibiotics as DID, and relative consumption of antibiotics as a percentage of penicillins consumption by chemical subgroups (ATC4)) • Consumption of cephalosporins (J01DB, J01DC, J01DD, J01DE and J01DI) (quantity of antibiotics as DID, and relative consumption of antibiotics as a percentage of cephalosporins consumption by chemical subgroups (ATC4)) • Consumption of other antimicrobials groups, namely antimycotics and antifungals (quantity of antimycotics and antifungals for systemic use as DID, and relative consumption as a percentage of the consumption of antimycotics and antifungals for systemic use, by chemical subgroups (ATC4)). The methods for calculation of consumption estimates generally align with those used by the AMC Network. The exception is the population estimates used in the denominator for calculations. The AMC Network applies population estimates from the World Bank, GLASS-AMC uses United Nations population estimates. The impact of this change in source of population data is explored in section 3.4.1. 3 4 1 Source of population data for consumption estimates Exploratory analyses were conducted using 2021 consumption data to examine the impact of a change in population data source. The population data for nine countries – Azerbaijan, Belarus, Bosnia and Herzegovina, Montenegro, Russian Federation, Serbia, Switzerland, Tajikistan and Türkiye – were considered in these analyses. In AMC Network reports, national population estimates are applied for Switzerland and Türkiye, rather than World Bank estimates. Table 22 shows differences in World Bank and United Nations population estimates for the seven countries currently using World Bank population estimates. Results are shown as absolute differences between the estimates and percentages of the World Bank population estimates. In 6 of the 7 countries, World Bank population estimates were lower than United Nations estimates. The largest differences were Belarus (2.85% lower) and Serbia (7.13% lower). 30 ANTIMICROBIAL MEDICINES CONSUMPTION (AMC) NETWORK Table 22 Differences in World Bank and United Nations 2021 population estimates for seven countries Country World Bank population estimates United Nations population estimates Difference (Word Bank − United Nations) % differencea,b AZE 10 145 212 10 296 374 −151 162 −1.49% BIH 3 263 459 3 295 841 −32 382 −0.99% BLR 9 340 314 9 606 437 −266 123 −2.85% MNE 620 173 628 205 −8 032 −1.30% RUS 143 446 060 145 472 994 −2 026 934 −1.41% SRB 6 844 078 7 331 946 −487 868 −7.13% TJK 9 749 625 9 643 597 106 028 1.09% a Total amounts and percentages may vary slightly due to rounding. b % difference = (World Bank − United Nations)/World Bank*100. The impact of a change from national estimates to United Nations population statistics for Switzerland and Türkiye is shown in Table 23. In both cases, national population estimates are higher than United Nations population estimates. The difference is more pronounced in the case of Türkiye, where national population estimates are 4.48% higher than United Nations population estimates. Table 23 Differences in national and United Nations 2021 population estimates for two countries Country National population estimates United Nations population estimates Difference (National – United Nations) % differencea,b SWI 8 738 791 8 670 795 67 996 0.78 TUR 88 417 642 84 459 174 3 958 468 4.48 a Total amounts and percentages may vary slightly due to rounding. b % difference = (National − United Nations)/World Bank*100 3 4 2 Impact of source of population data on estimates of total consumption of J01 antibacterials The impact of population data sources on the estimates of total consumption of J01 antibacterials is shown in Table 24. For 2021, World Bank population estimates were lower than United Nations population estimates in six countries (Table 24). The effect of the use of the lower population estimate is to increase the consumption estimate in DID. The increases are mostly small (< 2%), however in the case of Serbia, application of the World Bank population estimate gives a total consumption estimate 6.7% higher than using the United Nations population estimate. 31 ANTIMICROBIAL MEDICINES CONSUMPTION ACROSS THE AMC NETWORK, 2020–2021 Table 24 Differences in 2021 total consumption of J01 antibacterials, World Bank and United Nations population estimates, for seven countries Country DIDa Using World Bank population estimates Using United Nations population estimates Difference in DID (Word Bank − United Nations) % differenceb AZE 11.27 11.10 0.17 1.47% BIH 18.99 18.80 0.19 1.00% BLR 19.95 19.40 0.55 2.77% MNE 31.70 31.30 0.41 1.28% RUS 16.26 16.03 0.23 1.39% SRB 34.38 32.09 2.29 6.65% TJK 19.63 19.84 -0.22 −1.10% a Total amounts and percentages may vary slightly due to rounding. b % difference = (World Bank − United Nations)/World Bank*100 The impact of population data sources on the estimates of total consumption of J01 antibacterials in Switzerland and Türkiye is shown in Table 25. Applying higher national population estimates has the effect of lowering total consumption estimates. The difference is substantial in the case of Türkiye, where application of national population estimates gives an estimate of total consumption of J01 antibacterials that is 4.69% lower than that derived using United Nations population data. Table 25 Differences in 2021 total consumption of J01 antibacterials, national statistics and United Nations population estimates, for two countries Country DIDa Using national population estimates Using United Nations population estimates Difference in DID (National − United Nations) % differencea,b SWI 8.56 8.62 −0.07 −0.78% TUR 28.28 29.60 −1.33 −4.69% a Total amounts and percentages may vary slightly due to rounding. b % difference = (National − United Nations)/World Bank*100. These findings are relevant as countries move to AMC consumption calculated using the GLASS-IT platform. Those interpreting and using consumption estimates to inform national policies on access and use of antibiotics need to be aware of the data source used in the calculations, particularly in the situation that historical data based on World Bank population estimates are being compared with new GLASS-AMC estimates. The GLASS-IT platform will recalculate historical data and adjust populations used in the calculations to United Nations estimates, however this can only occur for historical data that are uploaded to the GLASS-IT platform. When all AMC network members have enrolled in GLASS-AMC, United Nations population estimates will be used in analyses of AMC Network data and reported in any future AMC Network reports. This will ensure consistency in estimates for the AMC Network and GLASS-AMC. 32 ANTIMICROBIAL MEDICINES CONSUMPTION (AMC) NETWORK 4. DISCUSSION This report extends the analyses of data from the 2022 AMC Network report (WHO Regional Office for Europe 2022a) and the 2019 and 2021 peer-reviewed articles by Robertson et al. (2019, 2021). The analyses focus on cross-national comparisons of consumption data for 2020 (13 AMC Network countries) and 2021 (10 countries). In 2020, consumption of J01 antibacterials ranged from 9.0 DID (Switzerland) to 34.3 DID (Kyrgyzstan), with median consumption across the 13 countries of 19.5 DID and population-weighted mean consumption of 21.8 DID. The comparable estimates in 2019 ranged from 10.6 DID to 33.2 DID, with a median consumption of 19.6 DID and a population-weighted mean consumption of 21.2 DID. For the 10 countries with 2021 data, consumption ranged from 8.6 DID (Switzerland) to 34.4 DID (Serbia), with median and population-weighted mean consumption of 19.3 DID and 20.3 DID, respectively. Analyses of population-weighted consumption estimates across the Network using three years of data, 2019–2021, suggest that there was increased consumption of J01 antibacterials in 2020 and subsequent reductions in consumption in 2021. The population-weighted pattern of increased consumption from 2019 to 2020 and then a decrease in 2021 was not consistent across all countries. Data from Belarus, Russian Federation and Tajikistan fit this pattern – showing increases in consumption from 2019 to 2020, then falling consumption levels in 2021. However, consumption in Serbia increased in each successive year from 26.6 DID in 2019 to 29.2 DID in 2020 and to 34.4 DID in 2021. In Türkiye, total consumption fell substantially between 2019 and 2020 (33.2 DID to 25.8 DID) before increasing in 2021 to 28.3 DID. There was considerable variability between countries in the relative consumption of the pharmacological subgroups of J01 antibacterials in both 2020 and 2021. The most notable change over the period 2019– 2021 across the Network was the increased relative consumption of the macrolides, lincosamides and streptogramins group (J01F) of agents. The AMC population-weighted estimates showed consumption increasing from 14% of total J01 consumption in 2019 to 20% in 2020, then falling to 15% in 2021. The same trend of increased antibacterial consumption between 2019 and 2020 was not observed in the European Union/European Economic Area (EU/EEA) countries of the WHO European Region. On the contrary, a significant decrease in antibacterial consumption at the country level was reported by the majority of EU/EEA countries for both the community and hospital sectors. ESAC-Net reported a 17.9% decrease in the EU/EEA population-weighted mean of total antibacterial consumption from 19.9 DID in 2019 to 16.4 DID in 2020 (European Centre for Disease Control, 2021). A systematic review of data from 20 countries globally showed a reduction in the utilization of health-care services during the COVID-19 pandemic (Moynihan et al., 2021). Reduced provision of health-care services directly impacts patients’ access to medicines, including in EU/EEA countries, where access to antimicrobials by prescription is strictly enforced. However, the situation is different in AMC Network countries, where the sale of antimicrobials without a prescription is still prevalent, despite national legislation. A recent study conducted in community pharmacies in nine AMC Network countries during the COVID-19 pandemic found substantial antimicrobial supply occurred without a prescription (WHO Regional Office for Europe, 2022b) This environment, alongside information 33 DISCUSSION widely disseminated about potential treatments for COVID-19, may have partially contributed to the observed increase in antimicrobial consumption in the countries of the AMC Network in 2020. Increases in consumption in 2020 coincide with the early phases of the COVID-19 pandemic, when several agents were being promoted as potentially useful to reduce hospitalizations and the severity of COVID-19 disease. COVID-19 is a viral infection, so increased use of antiviral agents might have been expected; however, COVID-19 may also be associated with secondary bacterial infections such as pneumonia (Morris et al., 2017). The macrolide antibiotic azithromycin was widely promoted as part of a treatment regimen for COVID-19 (Oliver and Hinks, 2020; Touret et al., 2020). Subsequently, a randomized controlled trial conducted in primary care settings failed to demonstrate that routine use of azithromycin reduced the time to recovery or the risk of hospitalization for people with suspected COVID-19 in the community (PRINCIPLE Trial Collaborative Group, 2021). However, this evidence was not published until March 2021. The findings of this trial and other published studies are likely to have contributed to the reduced consumption of macrolides including azithromycin in 2021. Further investigation at the country level is needed to understand the reasons for the patterns seen and the possible impact of the COVID-19 pandemic on the estimates. It is also worth noting that many AMC Network countries use import records for national AMC surveillance, which will be a proxy measure of antimicrobial consumption. During the COVID-19 pandemic, global shortages of medicines and health products may have further affected these estimates, leading some countries to increase their imports to prevent potential shortages. As a result, the increases observed in 2020 AMC data which are based on import records, may not necessarily reflect an actual increase in consumption. Therefore, these data should be interpreted within the context of the specific circumstances present in each individual country. Ten countries had consumption estimates available for all years 2014–2021. Three countries showed statistically significant increases in consumption of J01 antibacterials over the eight years of data collection – Azerbaijan (CAGR +8.4%), Bosnia and Herzegovina (+3.1%) and Russian Federation (+2.8%). Three countries showed statistically significant reductions in consumption over time – North Macedonia (−0.9%), Switzerland (−3.6%) and Türkiye (−2.9%). AMC Network population-weighted estimates of the relative consumption of Access, Watch and Reserve classification antibacterials from 2019–2021 show that Access agents represented 50% of consumption in 2019, 46% in 2020 and 50% in 2021. Watch group antibiotics constituted 46%, 52% and 49% of total consumption for those same years. Consumption of Reserve agents and unclassified antibacterials was low in all three years. Most countries showed patterns like the Network averages, namely decreases in relative consumption of Access agents from 2019 to 2020 and increases in 2021. This pattern of consumption is likely to be attributable to the increased consumption of Watch group macrolides, including azithromycin, in 2020 and reductions in 2021. In 2019, five AMC Network countries met WHO’s suggested national target of 60% of total consumption of antibacterials being derived from the Access list. Only Switzerland achieved this target in 2020 (63%); Belarus (66%) and Switzerland (65%) met it in 2021. The number of agents constituting the DU75% – by oral substance – across the AMC Network countries ranged from 5 to 10 in 2020 and 6 to 9 in 2021. There were six Watch agents in the population-weighted DU75% in both years. The most notable change between 2019 and 2020 was the increased relative consumption of azithromycin – rising from fourth to the most consumed oral antibiotic across the AMC Network in 2020. The pattern was consistent, with azithromycin included in the DU75% for 12 of the 13 Network countries in 2020, ranked first most consumed antibiotic in six countries and second in a further five countries. 34 ANTIMICROBIAL MEDICINES CONSUMPTION (AMC) NETWORK The scope of WHO’s GLASS has widened to include surveillance data on antimicrobial medicines consumption (GLASS-AMC). Network members are transitioning to data collection via the GLASS-IT platform. Analyses are broadly like those conducted by the AMC Network except that GLASS-AMC applies United Nations population estimates for its calculations. Since 2011, the AMC Network has used World Bank population estimates in calculations, apart from Türkiye and Switzerland, where national population estimates are applied. Exploratory analyses were conducted using 2021 consumption data to examine the impact of a change in population data source. In 6 of 7 countries, World Bank population estimates were lower than United Nations estimates, with the largest differences for Belarus (2.85% lower) and Serbia (7.13% lower). For Serbia, the total consumption estimate for 2021 was 6.7% higher using the World Bank population estimate rather than the United Nations population data. For Switzerland and Türkiye, national population estimates are higher than United Nations estimates; 4.48% higher in the case of Türkiye. For Türkiye, use of national population data results in an estimate of total consumption of J01 antibacterials that is 4.69% lower than that derived using United Nations population data. These findings are relevant as countries move to AMC consumption calculated using the GLASS-IT platform. Those interpreting and using consumption estimates to inform national policies on access and use of antibiotics need to be aware of the data sources used in the calculations, particularly in the situation that historical data based on World Bank population estimates are being compared with new GLASS-AMC estimates. The GLASS-IT platform will recalculate historical data and adjust populations used in the calculations to United Nations population statistics, however this can only occur for historical data that are uploaded to the GLASS-IT platform. As in previous AMC Network reports, the analyses focus on total consumption of antibacterials. Disaggregation of data to hospital and community sectors is not possible in most Network countries, but this remains an important area for future development as countries strengthen and enhance their surveillance capacity. The limitations of some of the data have implications for interpretation of results. Only medicines with an assigned ATC code and DDD are included in the analyses. Where there are medicines without codes consumed by the population, DID estimates will be underestimated. While import records have limitations, they will include the over-the-counter supply of antibacterials without prescription that occurs in some countries. Without information on indication for treatment, some results are difficult to interpret. A fuller interpretation of the consumption data requires an understanding of the local context. Further quantitative and qualitative studies conducted in primary care and hospital sectors may be needed to determine reasons for use, as well as doses and duration of treatments prescribed. Despite some limitations of the data used to estimate antibacterial consumption, it is important that local data are regularly analysed, reviewed and used in decision-making. The quality of the data is unlikely to improve unless the data are seen as relevant and useful for policy development and implementation. Missing information may provide the impetus for commitments to improve the scope and completeness of data collection. Dissemination of information on antibacterial consumption to clinicians and the public will heighten awareness of inappropriate use and problem prescribing and dispensing practices. Cross-national comparisons in this report allow benchmarking of activities across the AMC Network. Direct comparisons between estimates in 2020 and 2021 are hampered by differences in the countries included in the analyses – 13 countries in 2020 and 10 in 2021. However, substantial differences in the volumes and patterns of consumption between countries can suggest targets for further studies to understand better the use of these medicines in clinical practice. 35 DISCUSSION The transition to data collection and analysis using the GLASS-IT platform should not present significant methodological challenges for AMC Network countries. The information to be collected and analyses conducted are similar to those undertaken in the Network since 2011. When all AMC Network members have enrolled in GLASS-AMC, United Nations population estimates will be used in analyses of AMC Network data and reported in any future AMC Network reports. This will ensure consistency in estimates for the AMC Network and GLASS-AMC, and a common basis for promoting action at the country level and the development of interventions to improve the use of antibacterial agents. 36 ANTIMICROBIAL MEDICINES CONSUMPTION (AMC) NETWORK REFERENCES European Antimicrobial Resistance Collaborators (2022). The burden of bacterial antimicrobial resistance in the WHO European Region in 2019: a cross-country systematic analysis. Lancet Public Health. 7(11). doi: 10.1016/S2468-2667(22)00225-0. European Centre for Disease Prevention and Control, European Food Safety Authority Panel on Biological Hazards, European Medicines Agency Committee for Medicinal Products for Veterinary Use (2017). ECDC, EFSA and EMA joint scientific opinion on a list of outcome indicators as regards surveillance of antimicrobial resistance and antimicrobial consumption in humans and food-producing animals. EFSA Journal. 15(10):4993. doi: 10.2903/j.efsa.2017.5017. 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Azithromycin for community treatment of suspected COVID-19 in people at increased risk of an adverse clinical course in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial. Lancet. 397(10279):1063–74. doi: 10.1016/S0140- 6736(21)00461-X. Robertson J, Iwamoto K, Hoxha I, Ghazaryan L, Abilova V, Cvijanovic A et al. (2019). Antimicrobial medicines consumption in eastern Europe and central Asia – an updated cross-national study and assessment of quantitative metrics for policy action. Front Pharmacol. 9:1156. doi: 10.3389/ fphar.2018.01156. Robertson J, Vlahović-Palčevski V, Iwamoto K, Diaz Högberg L, Godman B, Monnet DL et al. (2021). Variations in the consumption of antimicrobial medicines in the European Region, 2014–2018: findings and implications from ESAC-Net and WHO Europe. Front Pharmacol. 12:639207 doi: 10.3389/ fphar.2021.765748. Touret F, Gilles M, Barral K, Nougairède A, van Helden J, Decroly E et al. (2020). In vitro screening of a FDA approved chemical library reveals potential inhibitors of SARS-CoV-2 replication. Sci Rep. 10:13093. doi: 10.1038/s41598-020-70143-6. WHO (2017). WHO methodology for a global programme on surveillance of antimicrobial consumption. Version 1.0. Geneva: World Health Organization. 37 REFERENCES WHO (2018). WHO report on surveillance of antibiotic consumption 2016–2018: early implementation. Geneva: World Health Organization (https://apps.who.int/iris/handle/10665/277359, accessed 9 June 2023). WHO (2019). Adopt AWaRe: handle antibiotics with care. In: AWaRe [website]. Geneva: World Health Organization (https://adoptaware.org/, accessed 9 June 2023). WHO (2020). GLASS methodology for surveillance of national antimicrobial consumption. Geneva: World Health Organization (https://apps.who.int/iris/handle/10665/336215, accessed 8 June 2023). WHO (2021a). Executive summary: the selection and use of essential medicines 2021: report of the 23rd WHO Expert Committee on the selection and use of essential medicines. Geneva: World Health Organization (https://apps.who.int/iris/handle/10665/345554, accessed 9 June 2023). WHO (2021b). 2021 AWaRe classification. WHO access, watch, reserve, classification of antibiotics for evaluation and monitoring of use. Geneva: World Health Organization (https://www.who.int/ publications/i/item/2021-aware-classification, accessed 9 June 2023). WHO Collaborating Centre for Drug Statistics Methodology (2022). Guidelines for ATC classification and DDD assignment 2023. Oslo: WHO Collaborating Centre for Drug Statistics Methodology (https:// www.whocc.no/atc_ddd_index_and_guidelines/guidelines/, accessed 19 June 2023). WHO Executive Board, 144 (2018). Proposed programme budget 2020–2021: thirteenth General Programme of Work, 2019–2023: WHO Impact Framework. Geneva: World Health Organization (https:// apps.who.int/iris/handle/10665/327341, accessed 9 June 2023). WHO Regional Office for Europe (2017). WHO Regional Office for Europe Antimicrobial Medicines Consumption (AMC) Network: AMC data 2011–2014. Copenhagen: WHO Regional Office for Europe (https:// apps.who.int/iris/handle/10665/329420, accessed 9 June 2023). WHO Regional Office for Europe (2020). WHO Regional Office for Europe Antimicrobial Medicines Consumption (AMC) Network: AMC data 2011–2017. Copenhagen: WHO Regional Office for Europe (https:// apps.who.int/iris/handle/10665/330466, accessed 9 June 2023). WHO Regional Office for Europe (2021). WHO Regional Office for Europe Antimicrobial Medicines Consumption (AMC) Network. AMC data 2014–2018. Copenhagen: WHO Regional Office for Europe (https:// apps.who.int/iris/handle/10665/342930, accessed 9 June 2023). WHO Regional Office for Europe (2022a). WHO Regional Office for Europe Antimicrobial Medicines Consumption (AMC) Network: AMC data 2019. Copenhagen: WHO Regional Office for Europe (https:// apps.who.int/iris/handle/10665/363394, accessed 9 June 2023). WHO Regional Office for Europe (2022b). Antimicrobials supplied in community pharmacies in eastern Europe and central Asia in the early phases of the COVID-19 pandemic. Copenhagen: WHO Regional Office for Europe (https://apps.who.int/iris/handle/10665/355796, accessed 9 June 2023). World Bank (2020). Population estimates and projections. In: World Bank [website]. Washington (DC) (https://databank.worldbank.org/source/population-estimates-and-projections, accessed 9 June 2022). Zarb P, Ansari F, Muller A, Vankerckhoven V, Davey PG, Goossens H (2011). Drug utilization 75% (DU75%) in 17 European hospitals (2000–2005): results from the ESAC-2 hospital care sub project. Curr Clin Pharmacol. 6(11):62–70. doi: 10.2174/157488411794941322. 38 ANTIMICROBIAL MEDICINES CONSUMPTION (AMC) NETWORK ANNEX 1. AGENTS INCLUDED IN THE 2021 AWaRe INDEX Table A1.1 Access antibiotics 2021 Antibiotic Class ATC code Listed on EML 2021 Amikacin Aminoglycosides J01GB06 Yes Amoxicillin Penicillins J01CA04 Yes Amoxicillin/clavulanic-acid Beta-lactam/beta-lactamase-inhibitor J01CR02 Yes Ampicillin Penicillins J01CA01  Yes Ampicillin/sulbactam Beta-lactam/beta-lactamase-inhibitor J01CR01 No Azidocillin Penicillins J01CE04 No Bacampicillin Penicillins J01CA06 No Benzathine-benzylpenicillin Penicillins J01CE08 Yes Benzylpenicillin Penicillins J01CE01 Yes Brodimoprim Trimethoprim-derivatives J01EA02 No Cefacetrile First-generation-cephalosporins J01DB10 No Cefadroxil First-generation-cephalosporins J01DB05 No Cefalexin First-generation-cephalosporins J01DB01 Yes Cefaloridine First-generation-cephalosporins J01DB02 No Cefalotin First-generation-cephalosporins J01DB03 No Cefapirin First-generation-cephalosporins J01DB08 No Cefatrizine First-generation-cephalosporins J01DB07 No Cefazedone First-generation-cephalosporins J01DB06 No Cefazolin First-generation-cephalosporins J01DB04 Yes Cefradine First-generation-cephalosporins J01DB09 No Cefroxadine First-generation-cephalosporins J01DB11 No Ceftezole First-generation-cephalosporins J01DB12 No Chloramphenicol Amphenicols J01BA01 Yes Clindamycin Lincosamides J01FF01 Yes Clometocillin Penicillins J01CE07 No Cloxacillin Penicillins J01CF02 Yes Dicloxacillin Penicillins J01CF01 No Doxycycline Tetracyclines J01AA02 Yes Epicillin Penicillins J01CA07 No Flucloxacillin Penicillins J01CF05 No Furazidin Nitrofuran derivatives J01XE03 No Gentamicin Aminoglycosides J01GB03 Yes Hetacillin Penicillins J01CA18 No Mecillinam Penicillins J01CA11 No Metampicillin Penicillins J01CA14 No Meticillin Penicillins J01CF03 No Metronidazole_IV Imidazoles J01XD01 Yes Metronidazole_oral Imidazoles P01AB01 Yes 39 ANNEX Antibiotic Class ATC code Listed on EML 2021 Nafcillin Penicillins J01CF06 No Nifurtoinol Nitrofuran derivatives J01XE02 No Nitrofurantoin Nitrofuran-derivatives J01XE01 Yes Ornidazole_IV Imidazoles J01XD03 No Ornidazole_oral Imidazoles P01AB03 No Oxacillin Penicillins J01CF04 No Penamecillin Penicillins J01CE06 No Phenoxymethylpenicillin Penicillins J01CE02 Yes Pivampicillin Penicillins J01CA02 No Pivmecillinam Penicillins J01CA08 No Procaine-benzylpenicillin Penicillins J01CE09 Yes Propicillin Penicillins J01CE03 No Secnidazole Imidazoles P01AB07 No Spectinomycin Aminocyclitols J01XX04 Yes Sulbactam Beta-lactamase-inhibitors J01CG01 No Sulfadiazine Sulfonamides J01EC02 No Sulfadiazine/tetroxoprim Sulfonamide-trimethoprim-combinations J01EE06 No Sulfadiazine/trimethoprim Sulfonamide-trimethoprim-combinations J01EE02 No Sulfadimethoxine Sulfonamides J01ED01 No Sulfadimidine Sulfonamides J01EB03 No Sulfadimidine/trimethoprim Sulfonamide-trimethoprim-combinations J01EE05 No Sulfafurazole Sulfonamides J01EB05 No Sulfaisodimidine Sulfonamides J01EB01 No Sulfalene Sulfonamides J01ED02 No Sulfamazone Sulfonamides J01ED09 No Sulfamerazine Sulfonamides J01ED07 No Sulfamerazine/trimethoprim Sulfonamide-trimethoprim-combinations J01EE07 No Sulfamethizole Sulfonamides J01EB02 No Sulfamethoxazole Sulfonamides J01EC01 No Sulfamethoxazole/trimethoprim Sulfonamide-trimethoprim-combinations J01EE01 Yes Sulfamethoxypyridazine Sulfonamides J01ED05 No Sulfametomidine Sulfonamides J01ED03 No Sulfametoxydiazine Sulfonamides J01ED04 No Sulfametrole/trimethoprim Sulfonamide-trimethoprim-combinations J01EE03 No Sulfamoxole Sulfonamides J01EC03 No Sulfamoxole/trimethoprim Sulfonamide-trimethoprim-combinations J01EE04 No Sulfanilamide Sulfonamides J01EB06 No Sulfaperin Sulfonamides J01ED06 No Sulfaphenazole Sulfonamides J01ED08 No Sulfapyridine Sulfonamides J01EB04 No Sulfathiazole Sulfonamides J01EB07 No Sulfathiourea Sulfonamides J01EB08 No Sultamicillin Beta-lactam/beta-lactamase-inhibitor J01CR04 No Talampicillin Penicillins J01CA15 No Tetracycline Tetracyclines J01AA07 No Thiamphenicol Amphenicols J01BA02 No Tinidazole_IV Imidazoles J01XD02 No Tinidazole_oral Imidazoles P01AB02 No Trimethoprim Trimethoprim-derivatives J01EA01 Yes 40 ANTIMICROBIAL MEDICINES CONSUMPTION (AMC) NETWORK Table A1.2 Watch antibiotics 2021 Antibiotic Class ATC code Listed on EML 2021 Arbekacin Aminoglycosides J01GB12 No Aspoxicillin Penicillins J01CA19 No Azithromycin Macrolides J01FA10 Yes Azlocillin Penicillins J01CA09 No Bekanamycin Aminoglycosides J01GB13 No Biapenem Carbapenems J01DH05 No Carbenicillin Penicillins J01CA03 No Carindacillin Penicillins J01CA05 No Cefaclor Second-generation-cephalosporins J01DC04 No Cefamandole Second-generation-cephalosporins J01DC03 No Cefbuperazone Second-generation-cephalosporins J01DC13 No Cefcapene-pivoxil Third-generation-cephalosporins J01DD17 No Cefdinir Third-generation-cephalosporins J01DD15 No Cefditoren-pivoxil Third-generation-cephalosporins J01DD16 No Cefepime Fourth-generation-cephalosporins J01DE01 No Cefetamet-pivoxil Third-generation-cephalosporins J01DD10 No Cefixime Third-generation-cephalosporins J01DD08 Yes Cefmenoxime Third-generation-cephalosporins J01DD05 No Cefmetazole Second-generation-cephalosporins J01DC09 No Cefminox Second-generation-cephalosporins J01DC12 No Cefodizime Third-generation-cephalosporins J01DD09 No Cefonicid Second-generation-cephalosporins J01DC06 No Cefoperazone Third-generation-cephalosporins J01DD12 No Ceforanide Second-generation-cephalosporins J01DC11 No Cefoselis Fourth-generation-cephalosporins to be assigned No Cefotaxime Third-generation-cephalosporins J01DD01 Yes Cefotetan Second-generation-cephalosporins J01DC05 No Cefotiam Second-generation-cephalosporins J01DC07 No Cefoxitin Second-generation-cephalosporins J01DC01 No Cefozopran Fourth-generation-cephalosporins J01DE03 No Cefpiramide Third-generation-cephalosporins J01DD11 No Cefpirome Fourth-generation-cephalosporins J01DE02 No Cefpodoxime-proxetil Third-generation-cephalosporins J01DD13 No Cefprozil Second-generation-cephalosporins J01DC10 No Cefsulodin Third-generation-cephalosporins J01DD03 No Ceftazidime Third-generation-cephalosporins J01DD02 Yes Cefteram-pivoxil Third-generation-cephalosporins J01DD18 No Ceftibuten Third-generation-cephalosporins J01DD14 No Ceftizoxime Third-generation-cephalosporins J01DD07 No Ceftriaxone Third-generation-cephalosporins J01DD04 Yes Cefuroxime Second-generation-cephalosporins J01DC02 Yes Chlortetracycline Tetracyclines J01AA03 No Cinoxacin Quinolones J01MB06 No Ciprofloxacin Fluoroquinolones J01MA02 Yes Clarithromycin Macrolides J01FA09 Yes Clofoctol Phenol derivatives J01XX03 No Clomocycline Tetracyclines J01AA11 No Delafloxacin Fluoroquinolones J01MA23 No 41 ANNEX Antibiotic Class ATC code Listed on EML 2021 Demeclocycline Tetracyclines J01AA01 No Dibekacin Aminoglycosides J01GB09 No Dirithromycin Macrolides J01FA13 No Doripenem Carbapenems J01DH04 No Enoxacin Fluoroquinolones J01MA04 No Ertapenem Carbapenems J01DH03 No Erythromycin Macrolides J01FA01 No Fidaxomicin Macrolides A07AA12 No Fleroxacin Fluoroquinolones J01MA08 No Flomoxef Second-generation-cephalosporins J01DC14 No Flumequine Quinolones J01MB07 No Flurithromycin Macrolides J01FA14 No Fosfomycin_oral Phosphonics J01XX01 No Fusidic-acid Steroid antibacterials J01XC01 No Garenoxacin Fluoroquinolones J01MA19 No Gatifloxacin Fluoroquinolones J01MA16 No Gemifloxacin Fluoroquinolones J01MA15 No Grepafloxacin Fluoroquinolones J01MA11 No Imipenem/cilastatin Carbapenems J01DH51 No Isepamicin Aminoglycosides J01GB11 No Josamycin Macrolides J01FA07 No Kanamycin_IV Aminoglycosides J01GB04 No Kanamycin_oral Aminoglycosides A07AA08 No Lascufloxacin Fluoroquinolones J01MA25 No Latamoxef Third-generation-cephalosporins J01DD06 No Levofloxacin Fluoroquinolones J01MA12 No Levonadifloxacin Fluoroquinolones J01MA24 No Lincomycin Lincosamides J01FF02 No Lomefloxacin Fluoroquinolones J01MA07 No Loracarbef Second-generation-cephalosporins J01DC08 No Lymecycline Tetracyclines J01AA04 No Meropenem Carbapenems J01DH02 Yes Metacycline Tetracyclines J01AA05 No Mezlocillin Penicillins J01CA10 No Micronomicin Aminoglycosides to be assigned No Midecamycin Macrolides J01FA03 No Minocycline_oral Tetracyclines J01AA08 No Miocamycin Macrolides J01FA11 No Moxifloxacin Fluoroquinolones J01MA14 No Nemonoxacin Quinolones J01MB08 No Neomycin_IV Aminoglycosides J01GB05 No Neomycin_oral Aminoglycosides A07AA01 No Netilmicin Aminoglycosides J01GB07 No Norfloxacin Fluoroquinolones J01MA06 No Ofloxacin Fluoroquinolones J01MA01 No Oleandomycin Macrolides J01FA05 No Oxolinic-acid Quinolones J01MB05 No Oxytetracycline Tetracyclines J01AA06 No Panipenem Carbapenems J01DH55 No Pazufloxacin Fluoroquinolones J01MA18 No 42 ANTIMICROBIAL MEDICINES CONSUMPTION (AMC) NETWORK Antibiotic Class ATC code Listed on EML 2021 Pefloxacin Fluoroquinolones J01MA03 No Penimepicycline Tetracyclines J01AA10 No Pheneticillin Penicillins J01CE05 No Pipemidic-acid Quinolones J01MB04 No Piperacillin Penicillins J01CA12 No Piperacillin/tazobactam Beta-lactam/beta-lactamase-inhibitor_anti-pseudomonal J01CR05 Yes Piromidic-acid Quinolones J01MB03 No Pristinamycin Streptogramins J01FG01 No Prulifloxacin Fluoroquinolones J01MA17 No Ribostamycin Aminoglycosides J01GB10 No Rifabutin Rifamycins J04AB04 No Rifampicin Rifamycins J04AB02 No Rifamycin_IV Rifamycins J04AB03 No Rifamycin_oral Rifamycins A07AA13 No Rifaximin Rifamycins A07AA11 No Rokitamycin Macrolides J01FA12 No Rolitetracycline Tetracyclines J01AA09 No Rosoxacin Quinolones J01MB01 No Roxithromycin Macrolides J01FA06 No Rufloxacin Fluoroquinolones J01MA10 No Sarecycline Tetracyclines J01AA14 No Sisomicin Aminoglycosides J01GB08 No Sitafloxacin Fluoroquinolones J01MA21 No Solithromycin Macrolides J01FA16 No Sparfloxacin Fluoroquinolones J01MA09 No Spiramycin Macrolides J01FA02 No Spiramycin/metronidazole Antibacterials_combinations J01RA04 No Streptoduocin Aminoglycosides J01GA02 No Streptomycin_IV Aminoglycosides J01GA01 No Streptomycin_oral Aminoglycosides A07AA04 No Sulbenicillin Penicillins J01CA16 No Tazobactam Beta-lactamase-inhibitors J01CG02 No Tebipenem Carbapenems J01DH06 No Teicoplanin Glycopeptides J01XA02 No Telithromycin Macrolides J01FA15 No Temafloxacin Fluoroquinolones J01MA05 No Temocillin Penicillins J01CA17 No Ticarcillin Penicillins J01CA13 No Tobramycin Aminoglycosides J01GB01 No Tosufloxacin Fluoroquinolones J01MA22 No Troleandomycin Macrolides J01FA08 No Trovafloxacin Fluoroquinolones J01MA13 No Vancomycin_IV Glycopeptides J01XA01 Yes Vancomycin_oral Glycopeptides A07AA09 Yes 43 ANNEX Table A1.3 Reserve antibiotics 2021 Antibiotic Class ATC code Listed on EML 2021 Aztreonam Monobactams J01DF01 No Carumonam Monobactams J01DF02 No Cefiderocola Other-cephalosporins J01DI04 Yes Ceftaroline-fosamil Fifth-generation cephalosporins J01DI02  No Ceftazidime/avibactam Third-generation-cephalosporins J01DD52 Yes Ceftobiprole-medocaril Fifth-generation cephalosporins J01DI01 No Ceftolozane/tazobactam Fifth-generation cephalosporins J01DI54 No Colistin_IV Polymyxins J01XB01 Yes Colistin_oral Polymyxins A07AA10 No Dalbavancin Glycopeptides J01XA04 No Dalfopristin/quinupristin Streptogramins J01FG02 No Daptomycin Lipopeptides J01XX09 No Eravacycline Tetracyclines J01AA13 No Faropenem Penems J01DI03 No Fosfomycin_IV Phosphonics J01XX01 Yes Iclaprim Trimethoprim-derivatives J01EA03 No Imipenem/cilastatin/relebactam Carbapenems J01DH56 No Lefamulin Pleuromutilin J01XX12 No Linezolid Oxazolidinones J01XX08 Yes Meropenem/vaborbactam Carbapenems J01DH52 Yes Minocycline_IV Tetracyclines J01AA08 No Omadacycline Tetracyclines J01AA15 No Oritavancin Glycopeptides J01XA05 No Plazomicin Aminoglycosides J01GB14 Yes Polymyxin-B_IV Polymyxins J01XB02 Yes Polymyxin-B_oral Polymyxins A07AA05 No Tedizolid Oxazolidinones J01XX11 No Telavancin Glycopeptides J01XA03 No Tigecycline Glycylcyclines J01AA12 No a New addition to EML 2021.

World Health Organization Regional Office for Europe UN City, Marmorvej 51, DK-2100 Copenhagen Ø, Denmark Tel.: +45 45 33 70 00 Fax: +45 45 33 70 01 Email: eurocontact@who.int Website: www.who.int/europe The WHO Regional Office for Europe The World Health Organization (WHO) is a specialized agency of the United Nations created in 1948 with the primary responsibility for international health matters and public health. The WHO Regional Office for Europe is one of six regional offices throughout the world, each with its own programme geared to the particular health conditions of the countries it serves. Member States Albania Andorra Armenia Austria Azerbaijan Belarus Belgium Bosnia and Herzegovina Bulgaria Croatia Cyprus Czechia Denmark Estonia Finland France Georgia Germany Greece Hungary Iceland Ireland Israel Italy Kazakhstan Kyrgyzstan Latvia Lithuania Luxembourg Malta Monaco Montenegro Netherlands (Kingdom of the) North Macedonia Norway Poland Portugal Republic of Moldova Romania Russian Federation San Marino Serbia Slovakia Slovenia Spain Sweden Switzerland Tajikistan Türkiye Turkmenistan Ukraine United Kingdom Uzbekistan