Articles Antibiotic use in eastern Europe: a cross-national database study in coordination with the WHO Regional Offi ce for Europe Ann Versporten, Ganna Bolokhovets, Lilit Ghazaryan, Vafa Abilova, Galina Pyshnik, Tijana Spasojevic, Irma Korinteli, Lul Raka, Baktygul Kambaralieva, Lidija Cizmovic, Angela Carp, Vesela Radonjic, Nargis Maqsudova, Hatice Demet Celik, Marina Payerl-Pal, Hanne Bak Pedersen, Nina Sautenkova, Herman Goossens, on behalf of the WHO/Europe-ESAC Project Group Summary Background There are no reliable data on antibiotic use in non-European Union (EU) southern and eastern European Lancet Infect Dis 2014 countries and newly independent states. We aimed to collect valid, representative, comparable data on systemic Published Online antimicrobial use in these non-EU countries of the WHO European region. March 20, 2014 http://dx.doi.org/10.1016/ S1473-3099(14)70071-4 Methods Validated 2011 total national wholesale antibiotic-use data of six southern and eastern European countries See Online/Comment and regions and seven newly independent states were analysed in accordance with the WHO anatomical therapeutic http://dx.doi.org/10.1016/ chemical (ATC)/defi ned daily doses (DDD) method and expressed in DDD/1000 inhabitants per day (DID). S1473-3099(14)70701-7 Laboratory of Medical Findings Total (outpatients and hospital care) antibiotic use ranged from 15·3 DID for Armenia to 42·3 DID for Turkey. Microbiology, Vaccine and Co-amoxiclav was mainly used in Georgia (42·9% of total antibiotic use) and Turkey (30·7%). Newly independent Infectious Disease Institute (VAXINFECTIO), University of states used substantial quantities of ampicillin and amoxicillin (up to 55·9% of total antibiotic use in Azerbaijan). Antwerp, Antwerp, Belgium Montenegro and Serbia were the highest consumers of macrolides (15·8% and 19·5% of total antibiotic use, (A Versporten MPH, respectively), mainly azithromycin. Parenteral antibiotic treatment is common practice: 46·4% of total antibiotic use in Prof H Goossens PhD); Health Azerbaijan (mainly ampicillin; 5·3 DID) and 31·1% of total antibiotic use in Tajikistan (mainly ceftriaxone; 4·7 DID). Technologies and Pharmaceuticals, Division of Health Systems and Public Interpretation This study provides publicly available total antibiotic-use data for 13 non-EU countries and areas of the Health, WHO Regional Offi ce WHO European region. These data will raise awareness of inappropriate antibiotic use and stimulate policy makers for Europe, Copenhagen, to develop action plans. The established surveillance system provides a method to develop quality indicators of Denmark (G Bolokhovets PhD, H Bak Pedersen MSc, antibiotic use and to assess the eff ect of policy and regulatory actions. N Sautenkova MPharm); Scientifi c Centre of Drug and Funding Netherlands Ministry of Health, Welfare, and Sport, and EU. Medical Technology Expertise of the Ministry of Health, Yerevan, Armenia Copyright ©2014. World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved. (L Ghazaryan MPharm); Ministry of Health of Azerbaijan Introduction 2011, to ESAC-Net of the European Centre for Disease Republic, Analytical Expertise Increasing levels of antimicrobial resistance have been Prevention and Control (ECDC).8 For European Union Centre for Medicines, Baku, Azerbaijan (V Abilova MPharm); spawned by rampant antibiotic use as shown both at the (EU) member countries and two European Economic Department on Organisation population1 and individual level.2 The European Antibiotic Area/European Free Trade Association countries of Medicines Provision, Resistance Surveillance network reported a Europe-wide (Norway and Iceland), ESAC-Net currently collects and Ministry of Health, Minsk, increase of antimicrobial resistance to Gram-negative analyses antimicrobial consumption data for both the Belarus (G Pyshnik); Agency for Medicines and Medical Devices 9 pathogens, with alarming evidence of increasing resistance community and the hospital sector. For the remaining of Bosnia and Herzegovina, to third-generation cephalosporins, fl uoroquinolones, and 11 southern and eastern European countries and Banja Luka, Bosnia and carbapenems in Escherichia coli and Klebsiella pneumoniae 12 former countries of the Soviet Union (excluding the Herzegovina in 2011.3 This threat is reinforced by globalisation and three Baltic states) of the WHO European region, valid (T Spasojevic MPharm); JSC “My family Clinic”, Tbilisi, Georgia migration because it favours spread of the resistance antibiotic-use data are not available. To address this gap, (I Korinteli MD); National problem. The World Economic Forum’s Global Risks 2013 the WHO Regional Offi ce for Europe (WHO Europe) and Institute of Public Health of report4 concluded that “while viruses may capture more the Laboratory of Medical Microbiology of the University Kosovo and Faculty of headlines, arguably the greatest risk of hubris to human of Antwerp, Belgium, established a surveillance network Medicine, University of Pristina, Pristina, Kosovo health comes in the form of antibiotic-resistant bacteria”. on antimicrobial consumption in non-EU countries of (L Raka PhD); CitiHope Sally Davies, England’s chief medical offi cer, stressed the the WHO European region. The overall aim of the project International, Bishkek, importance of international collaboration and the need for was to set up a sustainable network of national anti- Kyrgyzstan 5 (B Kambaralieva MSc); Agency a global approach to contain antibiotic resistance. microbial surveillance systems to collect valid, for Medicines and Medical Standardised and feasible methods to survey anti- representative, and comparable data on antimicrobial Devices of Montenegro, microbial use have been developed by the former use in non-EU countries of the WHO European region. Podgorica, Montenegro European Surveillance of Antimicrobial Consumption Our aims were to report on the method of data collection (L Cizmovic MPharm); Agency of Medicines, Chisinau, Moldova (ESAC) project.6,7 This project was transferred in June, employed and the encountered pitfalls; describe the www.thelancet.com/infection Published online March 20, 2013 http://dx.doi.org/10.1016/S1473-3099(14)70071-4 1 Articles (A Carp MPharm); Medicines characteristics of data sources, providers, and type of data We calculated the defi ned daily dose per package and Medical Devices Agency of available for the participating countries; assess data (DPP=[unit strength×pack size]/DDD). The DPP at Serbia, Belgrade, Serbia validity and representativeness at national level; do a product level was then multiplied with the (V Radonjic PhD); Avicenna Tajik State Medical University, cross-national comparison of 2011 antibiotic-use rates of corresponding number of nationally reported packages Dushanbe, Tajikistan 12 non-EU European countries and Kosovo; and provide of antimicrobial drugs brought and sold on the market (N Maqsudova MPharm); region-specifi c quality targets to improve antibiotic use. in 1 year (number of DDD at product level). Ministry of Health of Turkey, All references, including in the reference list, to “Kosovo” Denominator data used were the total number of Turkish Medicines and Medical Devices Agency, Ankara, Turkey mean “Kosovo (in accordance with UN Security Council inhabitants per year of a country (mid-year population) (H Demet Celik MScPharm); and resolution 1244 [1999])”. as provided by the respective national statistical offi ces Croatian Committee for or the United Nations Development Program.11 For Antibiotic Resistance Surveillance, Croatian Academy Methods Serbia, we consulted the CIA World Factbook because it for Medical Sciences, Zagreb, Participating countries provided denominator data for Serbia only (omitting Croatia (M Payerl-Pal MD) The ministries of health of the participating countries Kosovo; appendix). We subsequently calculated the Correspondence to: nominated national representatives to participate in this outcome measurement unit, DDD/1000 inhabitants per Prof Herman Goossens, WHO/Europe-ESAC project. Medicine agencies of health day (DID), at product level. Laboratory of Medical ministries from nine newly independent states (Armenia, Microbiology, Vaccine and Infectious Disease Institute Azerbaijan, Belarus, Georgia, Kyrgyzstan, Moldova, Data aggregation (VAXINFECTIO), Faculty of Tajikistan, Ukraine, and Uzbekistan) and six south and Data aggregation was done in accordance with the ATC Medicine and Health Science, eastern European countries (Albania, Bosnia and classifi cation.10 For macrolides, we attributed a classifi cation University of Antwerp—CDE, Universiteitsplein 1, Herzegovina, Macedonia, Montenegro, Serbia, Turkey), according to the mean plasma elimination half-life Room S6.26, B-2610 Antwerp, plus Kosovo, agreed to participate. We added validated subdividing them into short-acting (half-life <4 h), Belgium 2011 data for Croatia, a southeastern European country intermediate-acting (half-life 4–24 h), and long-acting (half- [email protected] not reporting 2011 data to ESAC-Net. life >24 h) macrolides.12 The quinolone substances were classifi ed according to three generations based on their For the CIA World Factbook see Data collection chemical structure and antimicrobial activity.13 Overall, http://cia-world-fact-book. The participating country representatives constructed an 144 unique antibiotic substances were used in 2011, fi ndthedata.org/d/d/2011 exhaustive validated national antimicrobial drug register ranging from 41 substances in Kosovo to 72