AMC data 2011–2017
WHO Regional Office for Europe
Antimicrobial Medicines Consumption (AMC) Network
OBIAL MEDICINES CONSUMPTION (AMC) NETWORK, AMC DATA 2011–2017
Office for Europe Antimicrobial
Medicines Consumption (AMC) Network
AMC data
2011–2017
of trends over time for key metrics of antibiotic consumption, considers new metrics to inform the responsible use of antibiotics and examines the impact of changes to defined daily doses that came into force on 1 January 2019.
The WHO Regional Office for Europe and its partners remain committed to supporting countries and areas in these endeavours through the activities of the WHO Europe Antimicrobial Medicines Consumption Network.
Keywords
ANTIMICROBIAL MEDICINES CONSUMPTION NATIONAL SURVEILLANCE NETWORKS ANTI-INFECTIVE AGENTS – THERAPEUTIC USE ANTIBIOTICS
EPIDEMIOLOGICAL MONITORING DATA COLLECTION
RESPONSIBLE USE OF ANTIBACTERIALS EASTERN EUROPE AND CENTRAL ASIA
ISBN 978-92-8905-474-4
© World Health Organization 2020
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Acknowledgements � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � vii Abbreviations � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � viii Summary � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � �ix 1� Introduction � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 1 2� The WHO Europe Antimicrobial Medicines Consumption (AMC) Network � � � � 4
2.1 Background . . . .4
2.2 Participating countries and areas . . . .5
3� Data collection and analysis � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 7 3.1 Methodology . . . .7
3.2 Data collection . . . .11
3.3 Data analysis . . . .12
3.4 Data interpretation . . . .14
4� Albania � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 18 4.1 Data source and years of data collection . . . .18
4.2 Estimates of volumes of consumption of antibacterials for systemic use (J01) . . . .18
4.3 Relative consumption by choice of agent. . . .20
4.4 The 10 most consumed agents . . . .22
4.5 Relative consumption of Core Access, Watch and Reserve groups of antibiotics . . . .23
4.6 Analyses based on DDDs applied in 2019 . . . .24
4.7 Discussion . . . .28
5� Armenia � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 31 5.1 Data source and years of data collection . . . .31
5.2 Estimates of volumes of consumption of antibacterials for systemic use (J01) . . . .31
5.3 Relative consumption by choice of agent. . . .33
5.4 The 10 most consumed agents . . . .35
5.5 Relative consumption of Core Access, Watch and Reserve groups of antibiotics . . . .36
5.6 Analyses based on DDDs applied in 2019 . . . .37
5.7 Discussion . . . .41
6� Azerbaijan � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 44 6.1 Data source and years of data collection . . . .44
6.2 Estimates of volumes of consumption of antibacterials for systemic use (J01) . . . .44
6.3 Relative consumption by choice of agent. . . .46
6.4 The 10 most consumed agents . . . .47
6.5 Relative consumption of Core Access, Watch and Reserve groups of antibiotics . . . .49
6.6 Analyses based on DDDs applied in 2019 . . . .50
6.7 Discussion . . . .54
7.3 Relative consumption by choice of agent. . . .58
7.4 The 10 most consumed agents . . . .59
7.5 Relative consumption of Core Access, Watch and Reserve groups of antibiotics . . . .61
7.6 Analyses based on DDDs applied in 2019 . . . .62
7.7 Discussion . . . .66
8� Bosnia and Herzegovina � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 69 8.1 Data source and years of data collection . . . .69
8.2 Estimates of volumes of consumption of antibacterials for systemic use (J01) . . . .69
8.3 Relative consumption by choice of agent. . . .71
8.4 The 10 most consumed agents . . . .72
8.5 Relative consumption of Core Access, Watch and Reserve groups of antibiotics . . . .73
8.6 Analyses based on DDDs applied in 2019 . . . .75
8.7 Discussion . . . .78
9� Georgia � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 81 9.1 Data source and years of data collection . . . .81
9.2 Estimates of volumes of consumption of antibacterials for systemic use (J01) . . . .81
9.3 Relative consumption by choice of agent. . . .83
9.4 The 10 most consumed agents . . . .84
9.5 Relative consumption of Core Access, Watch and Reserve groups of antibiotics . . . .86
9.6 Analyses based on DDDs applied in 2019 . . . .87
9.7 Discussion . . . .91
10� Kazakhstan � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 94 10.1 Data source and years of data collection . . . .94
10.2 Estimates of volumes of consumption of antibacterials for systemic use (J01) . . . .94
10.3 Relative consumption by choice of agent . . . .96
10.4 The 10 most consumed agents . . . .97
10.5 Relative consumption of Core Access, Watch and Reserve groups of antibiotics . . . .99
10.6 Analyses based on DDDs applied in 2019 . . . 100
10.7 Analysis by community and hospital sectors . . . 104
10.8 Discussion . . . 107
11� Kyrgyzstan � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 110 11.1 Data source and years of data collection . . . 110
11.2 Estimates of volumes of consumption of antibacterials for systemic use (J01) . . . 110
11.3 Relative consumption by choice of agent . . . 112
11.4 The 10 most consumed agents . . . 113
11.5 Relative consumption of Core Access, Watch and Reserve groups of antibiotics . . . 114
11.6 Analyses based on DDDs applied in 2019 . . . 116
11.7 Discussion . . . 119
12� Montenegro � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 121 12.1 Data source and years of data collection . . . 121
12.2 Estimates of volumes of consumption of antibacterials for systemic use (J01) . . . 121
12.3 Relative consumption by choice of agent . . . 122
12.4 The 10 most consumed agents . . . 124
12.5 Relative consumption of Core Access, Watch and Reserve groups of antibiotics . . . 125
12.6 Analyses based on DDDs applied in 2019 . . . 127
13� North Macedonia � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 137
13.1 Data source and years of data collection . . . 137
13.2 Estimates of volumes of consumption of antibacterials for systemic use (J01) . . . 137
13.3 Relative consumption by choice of agent . . . 138
13.4 The 10 most consumed agents – oral formulations . . . 140
13.5 Relative consumption of Core Access, Watch and Reserve groups of antibiotics . . . 141
13.6 Analyses based on DDDs applied in 2019 . . . 142
13.7 Discussion . . . 145
14� Republic of Moldova � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 147 14.1 Data source and years of data collection . . . 147
14.2 Estimates of volumes of consumption of antibacterials for systemic use (J01) . . . 147
14.3 Relative consumption by choice of agent . . . 149
14.4 The 10 most consumed agents . . . 150
14.5 Relative consumption of Core Access, Watch and Reserve groups of antibiotics . . . 152
14.6 Analyses based on DDDs applied in 2019 . . . 153
14.7 Discussion . . . 157
15� Russian Federation � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 160 15.1 Data source and years of data collection . . . 160
15.2 Estimates of volumes of consumption of antibacterials for systemic use (J01) . . . 160
15.3 Relative consumption by choice of agent . . . 162
15.4 The 10 most consumed agents . . . 163
15.5 Relative consumption of Core Access, Watch and Reserve groups of antibiotics . . . 165
15.6 Analyses based on DDDs applied in 2019 . . . 166
15.7 Analysis by community and hospital sectors . . . 170
15.8 Discussion . . . 174
16� Serbia � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 176 16.1 Data source and years of data collection . . . 176
16.2 Estimates of volumes of consumption of antibacterials for systemic use (J01) . . . 176
16.3 Relative consumption by choice of agent . . . 177
16.4 The 10 most consumed agents . . . 179
16.5 Relative consumption of Core Access, Watch and Reserve groups of antibiotics . . . 180
16.6 Analyses based on DDDs applied in 2019 . . . 182
16.7 Discussion . . . 185
17� Tajikistan � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 188 17.1 Data source and years of data collection . . . 188
17.2 Estimates of volumes of consumption of antibacterials for systemic use (J01) . . . 188
17.3 Relative consumption by choice of agent . . . 190
17.4 The 10 most consumed agents . . . 191
17.5 Relative consumption of Core Access, Watch and Reserve groups of antibiotics . . . 193
17.6 Analyses based on DDDs applied in 2019 . . . 194
17.7 Discussion . . . 198
18� Turkey � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 200 18.1 Data source and years of data collection . . . 200
18.2 Estimates of volumes of consumption of antibacterials for systemic use (J01) . . . 200
18.3 Relative consumption by choice of agent . . . 202
18.7 Analysis by community and hospital sectors . . . 210
18.8 Discussion . . . 214
19� Uzbekistan � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 217 19.1 Data source and years of data collection . . . 217
19.2 Estimates of volumes of consumption of antibacterials for systemic use (J01) . . . 217
19.3 Relative consumption by choice of agent . . . 218
19.4 The 10 most consumed agents . . . 219
19.5 Relative consumption of Core Access, Watch and Reserve groups of antibiotics . . . 221
19.6 Analyses based on DDDs applied in 2019 . . . 222
19.7 Discussion . . . 226
20� Kosovo1 � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 228 20.1 Data source and years of data collection . . . 228
20.2 Estimates of volumes of consumption of antibacterials for systemic use (J01) . . . 228
20.3 Relative consumption by choice of agent . . . 230
20.4 The 10 most consumed agents . . . 231
20.5 Relative consumption of Core Access, Watch and Reserve groups of antibiotics . . . 233
20.6 Analyses based on DDDs applied in 2019 . . . 234
20.7 Discussion . . . 238
21� Comparisons of 2017 antimicrobial medicines consumption across the AMC Network � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 241 21.1 Background . . . 241
21.2 Estimates of volumes of consumption of antibacterials for systemic use (J01) . . . 241
21.3 Relative consumption by choice of agent . . . 243
21.4 Relative consumption of Core Access, Watch and Reserve groups of antibiotics . . . 245
21.5 Analyses based on DDDs applied in 2019 . . . 246
21.6 Comparisons with ESAC-Net antimicrobial quality indicators . . . 248 22� Discussion � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 250
The WHO Regional Office for Europe would like to thank the WHO Europe Antimicrobial Medicines Consumption (AMC) Network members for providing antimicrobial consumption data and for their valuable contributions to this report.
The WHO Regional Office for Europe would also like to acknowledge the European Centre for Disease Prevention and Control, specifically Dr Klaus Weist and Dr Dominique Monnet, for their ongoing support and valued collaboration.
The database for data analysis was developed in conjunction with Public Health Expertise, Paris, France.
The report was written by Dr Jane Robertson, Ms Kotoji Iwamoto and Ms Hanne Bak Pedersen of the Health Technologies and Pharmaceuticals Programme, WHO Regional Office for Europe.
WHO Europe AMC Network activities are coordinated by the WHO Regional Office for Europe.
The financial support of the Ministry of Health, Welfare and Sport of the Netherlands and the German Collaboration Programme are gratefully acknowledged.
AMC antimicrobial medicines consumption AMR antimicrobial resistance
ATC Anatomical Therapeutic Chemical (classification system) AWaRe WHO Access, Watch and Reserve (classification)
DDD defined daily dose
DID defined daily doses per 1000 inhabitants per day 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
GAP WHO global action plan on antimicrobial resistance MDR-TB multidrug-resistant tuberculosis
SDGs (United Nations) Sustainable Development Goals TB tuberculosis
TESSy the European Surveillance System
Abbreviations of country and area names used in some tables and figures
ALB Albania ARM Armenia AZE Azerbaijan BLR Belarus
BIH Bosnia and Herzegovina GEO Georgia
KAZ Kazakhstan KGZ Kyrgyzstan
MDA Republic of Moldova MNE Montenegro
MKD North Macedonia RUS Russian Federation SRB Serbia
TJK Tajikistan TUR Turkey UZB Uzbekistan
KOS Kosovo2
2 All references to Kosovo in this document should be understood to be in the context of United Nations Security Council resolution 1244 (1999).
The WHO Europe Antimicrobial Medicines Consumption (AMC) Network aims to support all countries and areas 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).
Albania, Armenia, Azerbaijan, Belarus, Bosnia and Herzegovina, Georgia, Kazakhstan, Kyrgyzstan, Montenegro, North Macedonia, the Republic of Moldova, the Russian Federation, Serbia, Tajikistan, Turkey, Ukraine and Uzbekistan, as well as Kosovo,3 are members of the WHO Europe AMC Network.
This is the second WHO Europe AMC Network report. It sets out and analyses AMC data for 16 of the participating countries as well as for Kosovo3 in which the ministry of health and public health authorities approved data-sharing and publication. The report includes analyses of trends over time (2011–2017) for key metrics of antibacterial consumption, applies the WHO Core Access, Watch and Reserve classification of antibiotics, and examines the impact of proposed changes to defined daily doses (DDDs) in 2019 for some commonly used antibiotics. Results are compared with ESAC-Net quality indicator estimates for 2017. Analyses are presented for each AMC Network country and area separately, with comparisons across the AMC Network for selected metrics.
Key findings
Data on total consumption of antibacterials for systemic use (Anatomical Therapeutic Chemical (ATC) classification group J01) were available for 16 countries as well as for Kosovo.3 There was large variability in reported consumption of J01 antibacterials across the AMC Network – ranging from 8.5 defined daily doses per 1000 inhabitants per day (DID) (Azerbaijan) to 36.4 DID (Turkey) in 2017.
The population-weighted mean consumption across the 17 datasets was 21.1 DID (median consumption 20.3 DID). These consumption estimates were mostly lower than those reported in 2011 (range 6.4 DID Uzbekistan to 42.3 DID for Turkey, mean 23.6 DID) and in 2015 (range 8.0 DID for Azerbaijan to 41.5 DID for Turkey, mean 21.2 DID). ESAC-Net analyses also show considerable variability in total J01 consumption, ranging from 11.0 DID in the Netherlands to 34.1 DID in Spain in 2017 (ECDC, 2018).
The extent of consumption of parenteral formulations also varied widely – 4% in Turkey and 5% in Bosnia and Herzegovina, up to 45% in Kyrgyzstan and 50% in Uzbekistan in 2017.
The most commonly consumed subgroup of antibacterials was beta-lactams (ATC group J01C), with a range of 28.2% (Kazakhstan) to 54.3% (Kosovo3) of total J01 consumption in 2017. Cephalosporins (J01D) represented between 9% (Armenia) and 27.5% (Uzbekistan) of J01 consumption; quinolones (J01M) made up 22.9% of J01 consumption in Tajikistan.
very low consumption (< 0.1 DID) in several settings to 51% of cephalosporin consumption (4.9 DID) in Turkey. Third-generation agent consumption ranged from 22% (Bosnia and Herzegovina) to 88%
(Azerbaijan and Tajikistan) of total cephalosporin consumption and represented more than 50% of total cephalosporin consumption in nine of the 17 datasets.
Consumption of Core Access agents dominated in all AMC Network countries and areas, representing between 46.4% (Georgia) and 72.3% (Bosnia and Herzegovina) of total antibacterial consumption in 2017. Watch group agents represented between 22.9% (Bosnia and Herzegovina) and 44.4% (Tajikistan) of total consumption. Consumption of Reserve group agents was uniformly low across the Network.
Changes to DDDs implemented in January 2019 impacted on both total and relative consumption estimates, driven mostly by DDD changes for several commonly used beta-lactam penicillins.
Total J01 consumption estimates decreased from a range of 8.5–36.4 DID using 2018 DDD values to 7.8–31.0 DID using 2019 DDD values. The percentage reductions in total DIDs ranged from 8.0–15.9%, with mean DID reductions of 12.9%. However, there was limited impact on rankings from highest to lowest total consumption in DIDs. The data from 2015–2017 with 2019 DDD values applied will provide new baseline trend data against which data for future years will be compared.
It was possible to examine consumption patterns in community and hospital settings separately in four cases (Kazakhstan, Montenegro, the Russian Federation and Turkey). Most consumption occurs in the community and choices of antibiotics differ considerably in the two settings. This is important information as interventions are developed to target problem prescribing practices with antibiotics.
Conclusions
The results presented in this report document trends in consumption of antibacterial agents across parts of non-European Union Europe. The notable feature is the wide variability of estimates (both volumes of consumption and selection of agents) across the WHO Europe AMC Network. While the quantitative metrics presented have limited application in assessing the appropriateness of prescribing, they illustrate differing patterns of antibiotic consumption over time and point to potential problems in antibiotic use. The variability seen is unlikely to be explained by different patterns or burden of disease alone. The reasons for such variability require further investigation. The relatively higher levels of consumption of specific Watch group antibiotics suggest some targets for further investigation, interventions and stewardship activities supported by evidence-based guidelines and treatment algorithms.
A full exploration of reasons for the changes in consumption patterns reported in each of the 17 AMC Network countries and areas is beyond the scope of this report. However, the impact of locally produced antibiotics on treatment choices, pharmaceutical industry promotion, perverse incentives to prescribe and dispense antibiotics, and availability and use of up-to-date guidelines all need to be considered in developing interventions to improve antibiotic use.
Reference
ECDC (2018). Antimicrobial consumption. In: ECDC. Annual epidemiological report 2017. Stockholm:
ECDC (https://ecdc.europa.eu/sites/portal/files/documents/ESAC-NET-reportAER-2017-updated.
1. INTRODUCTION
The human and financial costs of antimicrobial resistance (AMR) are well recognized. Estimates suggest 700 000 deaths globally due to drug-resistant infections (O’Neill, 2016), with the world losing 3.8% of its annual gross domestic product by 2050 (World Bank, 2017) and concerns about the risks of AMR to the achievement of the United Nations Sustainable Development Goals (SDGs) (United Nations Interagency Coordination Group on Antimicrobial Resistance, 2017). Progress to address AMR relies on coordinated responses across the human and animal health sectors, as well as the environment, trade, intellectual property and innovation sectors (Wernli et al., 2017).
The momentum to address AMR continues to grow after the adoption of the WHO Global action plan on antimicrobial resistance (GAP) in 2015 (WHO, 2015), as reflected in the agendas of many high-level meetings such as the United Nations General Assembly in 2016 (United Nations, 2016), the G7 summit under the German Presidency in 2016, and again under German leadership the G20 summit in 2017.
The European Union (EU) has underscored the importance of the One Health approach, launching the One Health antimicrobial resistance action plan in 2017 (European Commission, 2017).
Member States adopted the GAP at the Sixty-eighth World Health Assembly in May 2015. The resolution urged Member States to implement the GAP, recognizing that it might need to be adapted to specific contexts and national priorities. Two specific objectives of the GAP are supported by the work described in this report on monitoring of AMC:
• strengthening surveillance and research (Objective 2)
• optimizing the use of antimicrobial medicines (Objective 4).
Data from selected countries and areas of the WHO Europe Antimicrobial Medicines Consumption (AMC) Network in 2011 were published in 2014 (Versporten et al., 2014) and an analysis of AMC data for 2011–2014 in 2017 (WHO Regional Office for Europe, 2017). Both analyses reported total consumption of Anatomical Therapeutic Chemical (ATC) J01 group antibacterials for systemic use (defined daily dose (DDD) per 1000 inhabitants per day (DID)) and the relative use of different pharmacological subgroups, including tetracyclines, penicillins, cephalosporins, aminoglycosides, macrolides and quinolones. These analyses also reported the relative consumption of agents recommended as second-line treatment choices, including cephalosporins (particularly third- and fourth-generation agents) and quinolones, on the basis that these metrics might focus attention on areas where antibiotic use could be improved.
Despite some differences in data sources used and differences in levels of expenditure on medicines between western and eastern Europe (Jakovljevic et al., 2016), comparisons between European Surveillance of Antimicrobial Consumption Network (ESAC-Net) and AMC data were presented, giving a pan-European perspective on antibiotic consumption (Versporten et al., 2014; WHO Regional Office for Europe, 2017; WHO, 2018).
Since then, a new classification of antibiotics introduced by WHO – the Access, Watch and Reserve groups of antibiotics (WHO, 2017a, 2017b) – and some significant changes to DDD values that took
increased the range of metrics that might be reported. The changes in DDD values also affect the interpretation of some existing measures of antibiotic consumption.
Data from the AMC Network in 2015 were published in 2019 (Robertson et al., 2019). This publication presented updated data from the WHO Europe AMC Network using cross-national and area comparisons of 2015 antibiotic consumption data for 16 Network members where the ministry of health and public health authorities approved data-sharing and publication. Consumption estimates for 2011 and 2015 were compared; the WHO Watch and Reserve classifications of antibiotics were applied, and the impact of changes to DDDs in 2019 were examined.
This report extends the reporting from the 2019 publication and includes trends over time between 2011 and 2017, with analyses using existing DDD values and repeated for the years 2015–2017 with the new 2019 DDDs applied. Both sets of data are presented to illustrate the impact of the changes in DDD values on volumes of consumption and proportion estimates. The data from 2015–2017 with 2019 DDD values applied will provide new baseline trend data against which data for future years will be compared.
References
European Commission (2017). A European One Health action plan against antimicrobial resistance.
Brussels: European Commission (https://ec.europa.eu/health/amr/action_eu_en, accessed 1 April 2019).
Jakovljevic M, Lazarevic M, Milovanovic O, Kanjevac T (2016). The new and old Europe: east–west split in pharmaceutical spending. Front Pharmacol. 7:18. doi:10.3389/fphar.2016.00018.
O’Neill J (2016). Review on Antimicrobial Resistance. Securing new drugs for future generations:
the pipeline of antibiotics. London: HM Government (https://amr-review.org/Publications.html, accessed 1 April 2019).
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.
United Nations (2016). General Assembly of the United Nations. High-level meeting on antimicrobial resistance. 21 September 2016. New York (NY): United Nations (https://www.un.org/pga/71/event- latest/high-level-meeting-on-antimicrobial-resistance/, accessed 1 April 2019).
United Nations Interagency Coordination Group on Antimicrobial Resistance (2017). AMR framework for action supported by the IACG. Working document. Geneva: World Health Organization (http://
www.who.int/antimicrobial-resistance/interagency-coordination-group/20170818_AMR_FfA_v01.
pdf, accessed 1 April 2019).
Versporten A, Bolokhovets G, Ghazaryan L, Abilova V, Pyshnik G, Spasojevic T et al., on behalf of the WHO/Europe-ESAC Project Group (2014). Antibiotic use in eastern Europe: a cross-national database study in coordination with the WHO Regional Office for Europe. Lancet Infect Dis. 14:381–7 (http://dx.doi.org/10.1016/S1473-3099(14)70071-4, accessed 1 April 2019).
Wernli D, Jørgensen PS, Harbarth S, Carroll SP, Laxminarayan R, Levrat N et al. (2017). Antimicrobial resist- ance: the complex challenge of measurement to inform policy and the public. PLoS Med. 14(8):e1002378 (https://doi.org/10.1371/journal.pmed.1002378, accessed 1 April 2019).
World Bank (2017). Drug-resistant infections: a threat to our economic future. Washington (DC): World Bank (http://documents.worldbank.org/curated/en/323311493396993758/pdf/114679-REVISED- v2-Drug-Resistant-Infections-Final-Report.pdf, accessed 1 April 2019).
World Health Organization (2015). Global action plan on antimicrobial resistance. Geneva: World Health Organization (http://www.who.int/antimicrobial-resistance/publications/global-action-plan/
en/, accessed 1 April 2019).
World Health Organization (2017a). Comprehensive review of antibiotic medicines: 21st expert committee on the selection and use of essential medicines. Geneva: World Health Organization (http://www.
who.int/selection_medicines/committees/expert/21/applications/comprehensive_antibiotics_rev/
en/, accessed 1 April 2019).
World Health Organization (2017b). The selection and use of essential medicines. Report of the WHO Expert Committee, 2017 (including the 20th WHO Model List of Essential Medicines and the 6th WHO Model List of Essential Medicines for Children). Geneva: World Health Organization (WHO Technical Report Series, No. 1006; https://apps.who.int/iris/bitstream/handle/10665/259481/9789241210157- eng.pdf?sequence=1, accessed 1 April 2019).
World Health Organization (2018). WHO report on surveillance of antibiotic consumption 2016–2018:
early implementation. Geneva: World Health Organization (https://www.who.int/medicines/areas/
rational_use/who-amr-amc-report-20181109.pdf?ua=1, accessed 1 April 2019).
WHO Collaborating Centre for Drug Statistics Methodology (2018). Updates included in the ATC/DDD Index. In: WHO Collaborating Centre for Drug Statistics Methodology [website]. Oslo: WHO Collaborating Centre for Drug Statistics Methodology (https://www.whocc.no/atc_ddd_index/updates_included_
in_the_atc_ddd_index/, accessed 1 April 2019).
WHO Regional Office for Europe (2017). Antimicrobial Medicines Consumption (AMC) Network. AMC data 2011–2014. Copenhagen: WHO Regional Office for Europe (http://www.euro.who.int/en/health-topics/
Health-systems/health-technologies-and-medicines/publications/2017/antimicrobial-medicines- consumption-amc-network.-amc-data-20112014-2017, accessed 1 April 2019).
2. THE WHO EUROPE ANTIMICROBIAL MEDICINES
CONSUMPTION (AMC) NETWORK
2�1 Background
The WHO Europe AMC Network is an initiative of the WHO Regional Office for Europe and aims to support all countries and areas in the Region that are not part of ESAC-Net, coordinated by the European Centre for Disease Prevention and Control (ECDC) in the EU. A brief description of the two networks follows, with a fuller description available in the Europe chapter of the WHO report on surveillance of antibiotic consumption 2016–2018: early implementation (WHO, 2018).
2�1�1 European Surveillance of Antimicrobial Consumption Network (ESAC-Net)
ESAC-Net is a network of national surveillance systems that provides reference data on antimicrobial consumption from the 28 Member States of the EU and two countries in the European Economic Area (EEA) (Iceland and Norway) using the European Surveillance System (TESSy) (ECDC, 2018, 2019).Nominated national focal points provide the antimicrobial consumption data.
ESAC-Net publishes annual reports of antimicrobial consumption data based on a standard reporting framework from the community and hospital sectors, using medicines sales or reimbursement data. Antimicrobial consumption data are collected using the ATC classification system and DDD methodology. The data are presented up to the fourth level of ATC coding (pharmacological subgroup).
In addition to annual reports, downloadable files show trends in consumption of antimicrobials and an interactive database can provide overviews of country data, data sources, geographical distribution of antibiotic consumption, rates and trends by country, and several quality indicators for antibiotic consumption in the community. Data are available from 1997 onwards.
Within the perspective of a One Health approach, a set of primary and secondary outcome indicators for antimicrobial consumption in the community and the hospital sector has been developed for humans and for the veterinary sector by the ECDC, the European Food and Safety Authority and the European Medicines Agency. The aim is to enable monitoring of antimicrobial consumption and tailor interventions for antimicrobial stewardship programmes (ECDC et al., 2017a, 2017b).
2�1�2 WHO Europe Antimicrobial Medicines Consumption Network
The WHO Europe AMC Network is an initiative of the WHO Regional Office for Europe that follows from a pilot project on data collection in 2011 involving the University of Antwerp (Belgium), the ECDC and the WHO Collaborating Centre for Drug Statistics Methodology (Norway). It aims to support countries and areas in the WHO European Region that are not part of ESAC-Net, currently consisting of 17 Member States as well as Kosovo.4 The methodology used by the WHO Europe AMC Network is closely aligned with that used by the ECDC to facilitate comparisons between EU and non-EU Member States in the Region. Data collection predates the formation of the WHO Europe AMC Network in several member countries and areas.
Data collection follows a standardized protocol, using a common Excel template based on a complete register of antimicrobial medicines with marketing authorization. The ATC classification system is used with data presented up to the fifth level of coding (individual medicine). Nominated focal points for antimicrobial consumption provide the consumption data.
2�2 Participating countries and areas
Albania, Armenia, Azerbaijan, Belarus, Bosnia and Herzegovina, Georgia, Kazakhstan, Kyrgyzstan, Montenegro, North Macedonia, the Republic of Moldova, the Russian Federation, Serbia, Tajikistan, Turkey, Ukraine and Uzbekistan, as well as Kosovo,2 currently are engaged in the WHO Europe AMC Network. Of these, 16 countries and Kosovo2 gave permission by the cut-off date of 20 March 2019 for the data to be published.
References
ECDC (2018). European Surveillance of Antimicrobial Consumption Network (ESAC-Net). In: European Centre for Disease Prevention and Control [website]. Solna: ECDC (https://ecdc. europa.eu/en/about- us/partnerships-and-networks/disease-and-laboratory-networks/esac-net, accessed 1 April 2019).
ECDC (2019). ESAC-Net Reporting Protocol 2018. Solna: ECDC (https://ecdc.europa.eu/en/publications- data/esac-net-reporting-protocol-2018, accessed 1 April 2019).
ECDC, European Food and Safety Authority, European Medicines Agency (2017a). ECDC/EFSA/
EMA second joint report on the integrated analysis of the consumption of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from humans and food-producing animals.
Joint Interagency Antimicrobial Consumption and Resistance Analysis (JIACRA) report. EFSA J.
15(7):4872. doi:10.2903/j. efsa.2017.4872.
ECDC, European Food and Safety Authority, European Medicines Agency (2017b). Joint scientific opinion on a list of outcome indicators as regards surveillance of antimicrobial resistance and antimicrobial consumption in humans and food-producing animals. Stockholm: European Centre for Disease Prevention and Control, European Food Safety Authority, European Medicines Agency;
2017 (https://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/j.efsa.2017.5017, accessed 1 April 2019).
World Health Organization (2018). WHO report on surveillance of antibiotic consumption 2016–2018:
early implementation. Geneva: World Health Organization (https://www.who.int/medicines/areas/
rational_use/oms-amr-amc-report-2016-2018/en/, accessed 1 April 2019).
3. DATA COLLECTION AND ANALYSIS
3�1 Methodology
3.1.1 Definitions
As in the previous WHO Regional Office for Europe report (WHO Regional Office for Europe, 2017) and in line with the WHO global protocol for data collection (WHO, 2016), a distinction is made between consumption data and antimicrobial-use data. This is done to recognize differences in the data sources and in the type of information that may be obtained from each approach.
• Consumption data are used to refer to estimates derived from aggregated data sources such as import or wholesaler data or aggregated health insurance data, where no information is available on the patients receiving the medicines or why the antimicrobials are used. These data sources provide a proxy estimate of use of antimicrobials. Consumption data may be presented as total consumption for a country/area or may be disaggregated by setting (community or hospital; public or private sectors).
• Antimicrobial-use data are used to refer to estimates derived from patient-level data. These may allow disaggregation based on patient characteristics (such as gender or age) or indications for which the medicine is being used.
3�1�2 Antimicrobials included in monitoring
The WHO Europe AMC Network programme focuses only on antimicrobials for systemic use – it excludes topical antimicrobials. The core set of agents that all countries and areas include in their monitoring is as follows:
• antibacterials (J01)
• antibiotics for alimentary tract and metabolism (A07AA)
• nitroimidazole derivatives against amoebiasis and other protozoal diseases (P01AB).
In addition, the WHO surveillance programme includes an optional list of antimicrobials that countries and areas may include in their surveillance programmes according to local needs and resources:
• antimycotics for systemic use (J02)
• antifungals for systemic use (D01BA)
• antivirals for systemic use (J05)
• drugs for treatment of tuberculosis (J04A)
• antimalarials (P01B).
This report builds on the early experience of data collection at country and area levels. It provides an analysis of data collected between 2011 and 2017 and includes several comparisons across the AMC Network for selected measures of AMC. The results mainly relate to analyses of antimicrobial agents in ATC group J01.
3�1�3 Health-care sectors monitored
In most of the countries and areas participating in the WHO Europe AMC Network, it is not possible to disaggregate data by sector (community or hospital; public or private), so total consumption data are reported in most cases. Analyses are also reported by community and hospital sectors separately where disaggregated data are available.
3�1�4 Measurements used
The WHO Europe AMC Network uses the ATC classification system, and the most commonly used measurement metric is the number of DDDs/1000 inhabitants per day. The ATC classification system allows flexibility in reporting by medicine or groups of medicines (WHO Collaborating Centre for Drug Statistics Methodology, 2018a). Medicines are classified in groups at five levels. Most antimicrobial agents are classified in ATC main group J: anti-infectives for systemic use.
The DDD is the assumed average maintenance dose per day for a medicine used for its main indication in adults (WHO Collaborating Centre for Drug Statistics Methodology, 2018b). The DDD is a technical unit of use and does not necessarily reflect the recommended or average prescribed daily dose. It is a useful metric that allows comparisons within and between countries and areas.
3�1�4�1 Changes to DDD values in 2019
In October 2017, following an application from the ECDC, the WHO International Working Group for Drug Statistics Methodology recommended changes to the DDDs for seven commonly used antibiotics (mainly penicillins) and endorsed new DDDs for oral colistin along with changes for several other products (Table 3.1) (WHO Collaborating Centre for Drug Statistics Methodology, 2018c). The changes were requested given evidence that current DDD allocations for commonly used medicines differed substantially from recommended doses and doses used in clinical practice. The DDD changes have been adopted fully since January 2019 and will affect estimates of total AMC and relative use of classes of antibiotics. The interpretation of national estimates and comparisons across the AMC Network over time will need to take account of these changed DDD values.
In addition to the changes shown in Table 3.1, new DDDs were assigned in 2019 for kanamycin oral (A07AA08), colistin oral (A07AA10), cefroxadine (J01DB11), cefteram (J01DD18), ceftriaxone and beta- lactamase inhibitor (J01DD63), tebipenem pivoxil (J01DH06), faropenem (J01DI03), midecamycin (J01FA03), lomefloxacin (J01MA07), gemifloxacin (J01MA15), garenoxacin (J01MA19), tosufloxacin (J01MA22) and delafloxacin (J01MA23).
Table 3.1 2019 changes to DDDs for commonly prescribed J01 antibacterials
ATCa code Medicine Previous DDDb New DDD
J01CA04 Amoxicillin 1 g Oc 1.5g O
J01CA04 Amoxicillin 1 g Pd 3g P
J01CA17 Temocillin 2 g 3 g P
J01CR02 Amoxicillin and beta-lactamase inhibitor 1 g O 1.5g O
J01CA01 Ampicillin 2 g P 6g P
J01DE01 Cefepime 2 g P 4g P
J01DH02 Meropenem 2 g P 3g P
J01MA02 Ciprofloxacin 0.5 g P 0.8g P
J01XB01 Colistin 3 MUe P 9 MU P
a ATC: Anatomical Therapeutic Chemical. b DDD: defined daily dose. c O: oral. d P: parenteral. e MU: million units.
Source: WHO Collaborating Centre for Drug Statistics Methodology (2018d).
3�1�4�2 Consumption according to the WHO Access, Watch and Reserve group classification
In April 2017, the Expert Committee on the Selection and Use of Essential Medicines recommended changes to the WHO model lists of essential medicines for adults (EML) and children (EMLc) following a comprehensive review of sections 6.2.1 (Beta-lactam medicines) and 6.2.2 (Other antibacterials) (WHO, 2017a, 2017b; Sharland et al., 2018). The Committee identified empirical first- and second-choice treatments for a number of common, community-acquired infections, focusing on treatment choices broadly applicable in most countries and areas.The Expert Committee also proposed a categorization of antibiotics into Access, Watch and Reserve groups (Table 3.2–3.5). Not all medicines on the model lists were assigned to the three groups, leaving a fourth “ungrouped” category, with the classification to be revised as additional clinical syndromes are reviewed. However, this classification could support antimicrobial stewardship efforts and focus attention on prescribing practices that should be reviewed further.
The Access group includes first- and second-choice antibiotics that should be widely available in all countries and areas. They should be affordable and quality-assured.
The Watch group includes antibiotic classes that generally are considered to have higher resistance potential and which remain recommended as first- or second-choice treatments but for a limited number of indications. These medicines should be “prioritized as key targets of local and national stewardship programmes and monitoring” (WHO, 2017a). The group includes the highest-priority agents on the critically important antibiotics list (World Organisation for Animal Health 2015; WHO, 2017c) and/or antibiotics that are at relatively high risk of selection of bacterial resistance.
The Reserve group of antibiotics includes antibiotics and antibiotic classes that the Expert Committee considered as last-resort agents, that is, those to be used when other alternatives would be inadequate or have already failed in, for example, serious life-threatening infections due to multidrug-resistant bacteria.
It is therefore useful to monitor the relative use of these classes of agents that should be used sparingly and judiciously to preserve their value for clinical medicine. Several agents in the Watch list are also included in the Access list but only for use in specific, limited indications. The analyses presented in this report use a Core Access group of agents that has no overlap with the Watch group antibiotics (see Table 3.3). The report also includes an assessment of the extent to which Watch and Reserve group antibiotics are included in the top 10 consumed oral and parenteral agents.
Table 3.2 WHO categories of antibiotics – descriptions
Group Definition
Access group First- and second-choice antibiotics that should be widely available in all countries and areas; they should be affordable and quality-assured
Watch group First- and second-choice antibiotics that should be used only for a specific, limited number of indications due to higher resistance potential
Reserve group Last-resort antibiotics that should be used only when other antibiotics have failed or for infections of multi-resistant bacteria
Ungrouped Medicines not specifically identified in the groups described above
Table 3.3 Access group
Medicine ATC codea Medicine ATC codea
Beta-lactam medicines Other antibacterials
amoxicillin J01CA04 amikacin J01GB06
amoxicillin + clavulanic acid J01CR02 azithromycinb –
ampicillin J01CA01 chloramphenicol J01BA01
benzathine benzylpenicillin J01CE08 ciprofloxacinb –
benzylpenicillin J01CE01 clarithromycinb –
cefalexin J01DB01 clindamycin J01FF01
cefazolin J01DB04 doxycycline J01AA02
cefiximeb – gentamicin J01GB03
cefotaximeb – metronidazole J01XD01, P01AB01
ceftriaxoneb – nitrofurantoin J01XE01
cloxacillin J01CF02 spectinomycin J01XX04
phenoxymethylpenicillin J01CE02 sulfamethoxazole + trimethoprim J01EE01
piperacillin + tazobactamb – vancomycin (oral, parenteral)b –
procaine benzylpenicillin J01CE09 – –
a ATC codes shown for medicines in the core access list – that is, no overlap with Watch group antibiotics.
b Watch group antibiotics included in the EML/EMLc only for specific, limited indications.
Table 3.4 Watch group
Medicines ATC code
Quinolones and fluoroquinolones
such as ciprofloxacin, levofloxacin, moxifloxacin, norfloxacin J01MA, J01MB Third-generation cephalosporins (with or without beta-lactamase inhibitor)
such as cefixime, ceftriaxone, cefotaxime, ceftazidime J01DD
Macrolides
such as azithromycin, clarithromycin, erythromycin J01FA
Glycopeptides
such as teicoplanin, vancomycin J01XA, A07AA09
Antipseudomonal penicillins with beta-lactamase inhibitor
such as piperacillin + tazobactam J01CR03, J01CR05
Carbapenems
such as meropenem, imipenem + cilastatin J01DH
Penems
such as faropenem J01DI03
Table 3.5 Reserve group
Medicine ATC code
Aztreonam J01DF01
Fourth-generation cephalosporins
such as cefepime J01DE
Fifth-generation cephalosporins
such as ceftaroline J01DI02, J01DI01, J01DI54
Fosfomycin IV J01XX01 (Only parenteral)
Oxazolidinone
such as linezolid J01XX08, J01XX11
Polymxyins
such as polymyxin B, colistin J01XB, A07AA10, A07AA05
Tigecycline J01AA12
Daptomycin J01XX09
Note: medicines not specifically identified in the groups described form an “ungrouped” medicines category.
A more detailed description of the WHO Access, Watch and Reserve (AWaRe) classification is available in the WHO global report on antimicrobial medicines consumption (WHO, 2018).
3�2 Data collection
3�2�1 Sources of antimicrobial consumption data 2011–2017
Most countries and areas participating in the WHO Europe AMC Network use import data (from customs records and declaration forms) as the source of information on antimicrobial consumption.
These are supplemented with sales records from market authorization holders or local manufacturing estimates where there is local pharmaceutical manufacturing. In some cases, data from wholesalers are used. Increasingly, data on antimicrobial use are available from health insurance programmes.
Table 3.6 summarizes the years of data, health-care sector coverage and data sources used in each of the settings included in this report.
Table 3.6 Sources of data used for consumption estimates (2011–2017)
Country or area Years of data Health-care sector
coverage Data sources for consumption estimates
Albania 2011–2017 Total care Import records
Armenia 2011–2017 Total care Import records
Sales records from local manufacturers
Azerbaijan 2011–2017 Total care Import records
Bosnia and Herzegovina 2011–2017 Total care Sales records of wholesalers and local manufacturers
Belarus 2011–2015 Total care Import records
Sales records from local manufacturers
Georgia 2011–2017 Total care Import records
Kazakhstan 2012–2014
2015–2017
Total care Community and hospitala
Import records VIORTIS
Kyrgyzstan 2011–2017 Total care Import records
Country or area Years of data Health-care sector
coverage Data sources for consumption estimates
Montenegro 2011–2017 Community and
Hospital Sales records from wholesalers
North Macedonia 2012–2017 Community Health insurance records
Republic of Moldova 2011–2017 Total care Import records
Manufacturing records from local manufacturers
Russian Federation 2011–2017 Community and
hospital IQVIA
Serbia
Serbia excluding Kosovob Kosovob
2011–2017 2011–2017
Total care Total care
Sales records from marketing authorization holders
Import records
Tajikistan 2011–2017 Total care Import records
Certification records
Turkey 2011–2012
2013–2017
Community Community and hospital
IQVIA
Wholesaler records from pharmaceutical track and trace system
Uzbekistan 2011–2017 Total care Import records
Sales records from local manufacturers
a Commercial data source provides coverage of around 80–85% of hospital and community sales.
b All references to Kosovo in this publication should be understood to be in the context of United Nations Security Council resolution 1244 (1999).
3�3 Data analysis
3�3�1 Consumption estimates
Once the datasets are agreed, the WHO regional team analyses the data. The number of packages of each product is multiplied by the number of DDDs per package to calculate the total number of DDDs for each product. These are aggregated to give the total number of DDDs at the desired ATC code level.
Population-adjusted estimates of consumption are automatically calculated with embedded macros for calculation of consumption estimates in DDD per 1000 inhabitants per day (DID).
3�3�2 Metrics reported
The use of the ATC classification permits analyses at five different levels – from main class (level 1) to individual medicine (level 5). The AMC data for ATC category J01 are analysed to give country- or area-specific trends in antimicrobial consumption and trends across the AMC Network.
This report focuses on five types of key measure used to examine trends over time (Table 3.7):
• volume of consumption measures, reported as numbers of DID using DDD values relevant to the specific year of data (2011–2017) then applying the DDD values implemented in January 2019;
• relative consumption measures, expressed as a percentage of total consumption of a group of antimicrobials;
• the agents consumed, reflecting the choice of specific antimicrobial agents within a class and allowing more focused assessment of whether the choices align with recommended best practices and clinical practice guidelines;
Table 3.6 contd
• consumption according to the WHO AWaRE group classification; and
• utilization of the 10 most consumed agents (oral and parenteral agents separately).
Table 3.7 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 DIDa Total consumption of J01 antibacterials by pharmacological subgroup:
• tetracyclines (J01A)
• amphenicols (J01B)
• beta-lactams (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 by choice of agent
Relative consumption of agents of cephalosporins by generation:
• choice of first-generation cephalosporins (J01DB)
• choice of second-generation cephalosporins (J01DC)
• choice of third-generation cephalosporins (J01DD)
• choice of fourth-generation cephalosporins (J01DE)
DID, %
Relative consumption of agents within fluoroquinolones (J01MA) DID, %
Relative consumption of WHO Core Access, Watch, Reserve antibioticsb
Relative consumption of Core Access agents, Watch group agents, Reserve group agents % The 10 most consumed agents
The 10 most consumed agents – oral formulation DID, %
The 10 most consumed agents – parenteral formulation DID, %
a DID: DDD/1000 inhabitants per day.
b Total consumption of antibiotics for this calculation includes J01, vancomycin (A07AA09), colistin (A07AA10), polymyxin B (A07AA05) and metronidazole (P01AB01).
3�3�2�1 Route of administration
Oral administration is generally regarded as the most acceptable and economical method of administration of antimicrobials. Hospitalized patients initially on intravenous antibiotics can often safely be switched to an oral equivalent once they are clinically stable. Oral medication is associated with fewer complications, lower health-care costs and earlier hospital discharge. Nevertheless, it must be recognized that there may also be cultural and medical practice traditions that favour use of parenteral formulations in some settings.
This report includes analyses of use of oral and parenteral formulations for J01 medicines. Where use of parenteral formulations is comparatively high, there may be opportunities to increase use of oral formulations without loss of clinical efficacy.
3�3�2�2 Total consumption in DDDs per 1000 inhabitants per day
The DDD per 1000 inhabitants per day (abbreviated to DID) is the most commonly reported metric of antimicrobial consumption and the most frequently used measure in cross-national comparisons (Versporten et al., 2014; WHO Regional Office for Europe, 2017; ECDC, 2019).
It should be noted that only medicines assigned an ATC code and DDD are included in the analyses reported here. Several medicines without such codes are consumed by the population in some countries and areas of the WHO Europe AMC Network. Exclusion of these medicines means that data are missing in the numerator for the calculation, and the resulting DID estimates will underestimate total antimicrobial consumption in the country/area.
3�3�2�3 Quinolones and cephalosporins
Quinolones and cephalosporins are broad-spectrum antibiotics and are considered second-line antibiotics in most prescribing guidelines (Adriaenssens et al., 2011). Their use should therefore be restricted to ensure availability as second-line therapy should first-line antibiotics fail.
WHO identifies fluoroquinolones, third- and fourth-generation cephalosporins, macrolides and glycopeptides as being of highest priority for risk management to ensure that critically important antimicrobials are used prudently both in human and veterinary medicine (World Organisation for Animal Health, 2015; WHO, 2017c).
Third- and fourth-generation cephalosporins have a broader spectrum of activity than first- and second-generation agents, with enhanced coverage of both Gram-positive and Gram-negative organisms. Third-generation cephalosporins and fluoroquinolones are part of the WHO Watch group of antibiotics (see Table 3.4) while fourth- and fifth-generation cephalosporins are included in the WHO Reserve group of agents (Table 3.5).
3�3�2�4 WHO Access, Watch and Reserve agents
For the preceding relative use measures, the denominator for calculation of the relative proportions of consumption is total J01 consumption. The Access, Watch and Reserve groups include several agents other than those in the J01 category, namely:
• metronidazole (oral) – ATC code P01AB01
• vancomycin (oral) – A07AA09
• polymyxin B (oral) – A07AA10
• colistin (oral) – A07AA05.
Total consumption of antibiotics for this calculation therefore includes J01, vancomycin (A07AA09), colistin (A07AA10), polymyxin B (A07AA05) and metronidazole (P01AB01).
3�4 Data interpretation
For a correct assessment of the magnitude and trends of antimicrobial consumption in the country or area and to allow comparison of results across the AMC Network and with other international data sets, the data are required to be both valid and reliable. The validity and reliability of data may be compromised at different points, however. These include:
• incomplete registration of antimicrobial products in circulation in the country or area
• incomplete capture and reporting of data
• double counting of medicines from different data sources
• errors in data entry that were not identified during data validation
• failure to account adequately for export of locally produced antimicrobial agents
• data excluded from calculations where no ATC or DDD is assigned for the medicine.
Together, these errors will affect the absolute values for antimicrobial consumption (measured in DID).
Incomplete data capture may occur when not all wholesalers provide data on products sold.
Sales data from local manufacturers need to distinguish between medicines for local consumption and medicines exported.
No ATC or DDD is assigned to a considerable number of products in several countries and areas participating in the WHO Europe AMC Network. Consumption of these medicines is excluded from the analyses reported here, meaning that total consumption estimates presented will underestimate actual consumption of antibacterials. The WHO Regional Office for Europe is working with participants in the WHO Europe AMC Network and the WHO Collaborating Centre for Drug Statistics Methodology to identify products without codes and to resolve these for future analyses.
3�4�1 Import data
An issue with data derived from importation records is that the estimates will be affected by the cycles of procurement and delivery. This may give rise to fluctuations in estimates of consumption that do not relate to use of antibacterials by patients and health-care facilities.
Import cycles are also likely to mean that different products are received at different times, so relative use estimates may also be affected. Notwithstanding these limitations, it is reasonable to assume that over a longer period the relative use estimates will stabilize and more closely reflect the relative consumption of different antibacterial agents. Consequently, trends over time need to be interpreted carefully. In general, import data should not be used to make comparisons on monthly or quarterly consumption.
The analyses in this report provide annual consumption estimates. The fluctuations in total consumption estimates from several countries and areas, however, suggest that import cycles may contribute in part to the patterns of consumption shown. In the absence of universal health coverage or e-prescribing, widespread availability of antibiotics without prescription, few mechanisms to engage private wholesalers and limited ability to disaggregate data to hospital and community sectors, import records remain the most feasible data source in most AMC Network countries and areas.
3�4�2 Information value
The data presented may not yet be optimal, or systemic issues may lead to biased estimates, but recognizing these limitations may encourage the use of different data sources, such as wholesaler rather than import data. Later, as information systems develop, it may be possible to derive consumption estimates from reimbursement records from health insurance agencies and e-prescribing platforms.
Already the situation is changing, with several countries and areas now reporting data disaggregated to community and hospital sectors and a number with the ability to use health insurance data to assess patterns of use of antimicrobials.
Even with the data limitations, the variability of consumption patterns within and between countries and areas 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.
