Antimicrobial resistance and antimicrobial consumption in Europe Dominique L. Monnet, on behalf of ECDC Antimicrobial Resistance and Healthcare-Associated Infections (ARHAI) Programme Vilnius, 28 November 2017
ECDC European Centre for Disease Prevention and Control An agency of the European Union, located in Stockholm, Sweden Founded in 2005; nearly 300 employees in 2015 Mandate to identify, assess and communicate current and emerging threats to human health from communicable diseases European Union (EU) (28) and European Economic Area (EEA) (3) = 31 countries with a total of more than 500 million people www.ecdc.europa.eu
Antimicrobial Resistance and Healthcare- Associated Infections (ARHAI) Networks European Antimicrobial Resistance Surveillance Network (EARS-Net) (formerly EARSS, integrated in January 2010) European Surveillance of Antimicrobial Consumption Network (ESAC-Net) (formerly ESAC, integrated in July 2011) Healthcare-Associated Infections surveillance Network (HAI-Net) (formerly HELICS / IPSE, integrated in July 2008) www.ecdc.europa.eu
AMR Antimicrobial resistance
Antimicrobial resistance: what does it really mean? Several, inter-related compartments of healthcare, (i.e. patients in primary care, hospitals, nursing homes and long-term care facilities), food animals, food, environment Many types of human infections, i.e. respiratory tract, urinary tract, skin and soft tissue, bloodstream, surgical site, related to medical devices, etc.) Many bacteria/microorganisms Many antimicrobials and mechanisms of resistance Patients with infections due to resistant bacteria!
https://antibiotic.ecdc.europa.eu/en/patient-stories
Burden of antimicrobial resistance (AMR) for the EU/EEA 25 000 deaths each year in the EU/EEA attributable to 5 multidrug-resistant bacteria 4 main healthcare-associated infections (HAIs) Update: 2018 Source: ECDC, 2009. In: http://ecdc.europa.eu/en/publications/publications/0909_ter_the_bacterial_challenge_time_to_react.pdf
Source: ECDC, 2015.
Hospitals Food animals Photo: US Dept. of Agriculture Photo: Luis García
2 nd Joint Interagency Antimicrobial Consumption and Resistance Analysis (JIACRA) Report Source: ECDC, EFSA & EMA, 2017. EFSA Journal, 27 July 2017. http://onlinelibrary.wiley.com/doi/10.2903/j.efsa.2017.4872/epdf 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 Humans + Animals = One Health
Biomass-corrected antimicrobial consumption in humans and animals, EU/EEA, 2014 Source: ECDC, EFSA & EMA, 2017. EFSA Journal, 27 July 2017. http://onlinelibrary.wiley.com/doi/10.2903/j.efsa.2017.4872/epdf Humans: 124 mg/kg (range: 50 182 mg/kg) Animals: 152 mg/kg (range: 3 419 mg/kg) * Humans: community consumption only
Biomass-corrected consumption of selected antimicrobial groups in humans and animals, EU/EEA, 2014 3rd- and 4th-generation cephalosporins Fluoroquinolones and other quinolones Humans Animals Source: ECDC, EFSA & EMA, 2017. EFSA Journal, 27 July 2017. http://onlinelibrary.wiley.com/doi/10.2903/j.efsa.2017.4872/epdf * Humans: community consumption only
Joint Interagency Antimicrobial Consumption and Resistance Analysis (JIACRA): example Poultry Quinolone consumption and probability of resistance to quinolones in Campylobacter jejuni from poultry, EU/EEA, 2014 OR = 2.71 [1.57 5.63], p < 0.001 Each dot represent one country. Source: EFSA Journal, 27 July 2017.
Community
Defined daily doses (DDD) per 1000 inh. and per day Packages per 1000 inh. and per day Sweden Sweden Denmark Estonia Finland Norway Finland * Total care data, including the hospital sector. Reimbursement data (i.e. not including consumption without a prescription and other non-reimbursed courses). Spain Luxembourg Greece Consumption of antibiotics for systemic use (ATC group J01) in the community, EU/EEA, 2012-2016 Source: ESAC-Net, 2017. The symbols and indicate a significant increasing or decreasing trend for the period 2012-2016, respectively.
Streptococcus pneumoniae: percentage of invasive isolates not susceptible to macrolides; EU/EEA, 2015 Update with 2016 data: 15 Nov. 2017 Source: EARS-Net, 2016 The symbols and indicate a significant increasing or decreasing trend for the period 2012-2015, respectively. These trends were calculated on laboratories that consistently reported during this period.
Escherichia coli: percentage of invasive isolates resistant to third-generation cephalosporins; EU/EEA, 2015 Source: EARS-Net, 2016 The symbols and indicate a significant increasing or decreasing trend for the period 2012-2015, respectively. These trends were calculated on laboratories that consistently reported during this period.
Escherichia coli: percentage of invasive isolates resistant to fluoroquinolones; EU/EEA, 2015 Source: EARS-Net, 2016 The symbols and indicate a significant increasing or decreasing trend for the period 2012-2015, respectively. These trends were calculated on laboratories that consistently reported during this period.
Joint Interagency Antimicrobial Consumption and Resistance Analysis (JIACRA): Results of partial least square path modeling (PLS-PM) of fluoroquinolone consumption and fluoroquinoloneresistant Escherichia coli Source: EFSA Journal, 27 July 2017.
Compartments of antimicrobial resistance H R E. coli HA-MRSA R Enterobacter R Klebsiella pneumoniae Clostridium difficile R Pseudomonas aeruginosa R Acinetobacter baumannii R Strep. pneumoniae R Salmonella R Campylobacter R E. coli CA-MRSA R Strep. pyogenes R Haem. influenzae R Salmonella R Campylobacter R E. coli LA-MRSA (mostly CC398)
Hospitals Photo: Luis García
Comparing the burden of healthcareassociated infections (HAIs) with other infectious diseases (BCoDE project 2015) Healthcare-associated infections account for twice the burden of 31 other infectious diseases Burden of HAIs 2011-2012 * Burden of 5 top ranking infectious diseases from BCoDE 2009-2013 ** HA, Healthcare-associated; DALYs: Disability-Adjusted Life Years Source: *Cassini A, et al. PLoS Med 2016;13(10):e1002150 (18 October 2016) ** Cassini A, et al. PLoS Med (submitted).
Healthcare-associated infections, antimicrobial resistance: Overlapping, but not identical Healthcareassociated infections Antimicrobial resistance Community-acquired infections
Staphylococcus aureus: % of invasive isolates with resistance to meticillin (MRSA), EU/EEA, 2013 & 2016 2013 2016 Source: EARS-Net, 2017. The symbols and indicate a significant increasing or decreasing trend for the period 2013-2016, respectively. These trends were calculated on laboratories that consistently reported during this period.
Klebsiella pneumoniae: % of invasive isolates with combined resistance* EU/EEA, 2013 & 2016 2013 *Third-generation cephalosporins, fluoroquinolones and aminoglycosides 2016 Source: EARS-Net, 2017. The symbols and indicate a significant increasing or decreasing trend for the period 2013-2016, respectively. These trends were calculated on laboratories that consistently reported during this period.
Klebsiella pneumoniae: % of invasive isolates with resistance to carbapenems EU/EEA, 2013 & 2016 2013 2016 Source: EARS-Net, 2017. The symbols and indicate a significant increasing or decreasing trend for the period 2013-2016, respectively. These trends were calculated on laboratories that consistently reported during this period.
Source: EARS-Net and CAESAR, 2017. *European Health Information Gateway (https://gateway.euro.who.int/en/) Enerobacteriaceae: carbapenem resistance (%), Europe*, 2016 E. coli K. pneumoniae
Carbapenem-resistant infections: a challenge for appropriate patient therapy Courtesy: C. Giske. Karolinska University Hospital, Stockholm, Swede.n Photo: www.microbiologie.info.
Mohammed (United Kingdom) https://storify.com/eaad_eu/patient-stories
Joint Interagency Antimicrobial Consumption and Resistance Analysis (JIACRA): example Humans Carbapenem consumption and probability of resistance to carbapenems in invasive Klebsiella pneumoniae from humans, EU/EEA, 2015 OR = 1.23 [95% CI: 1.08 1.42], p = 0.002 Each dot represent one country. Source: EFSA Journal, 27 July 2017.
Consumption of last-line antibiotics in the hospital sector, EU/EEA, 2012-2016 Carbapenems (DDD per 1000 inh. and per day) Polymyxins (mainly colistin) (DDD per 1000 inh. and per day) Bulgaria Latvia Hungary Lithuania Slovakia Romania Estonia Bulgaria Denmark Ireland * Cyprus and Romania: total care data, including consumption in the community. These data were not used to calculate the EU/EEA populationweighted average. Croatia France Slovenia Hungary Malta (a) Finland: data include consumption in remote primary healthcare centres and nursing homes. (b) Portugal: data relate to public hospitals only. Malta Cyprus Portugal (b) Romania Italy Slovakia Greece Source: ESAC-Net, 2017. The symbols and indicate a significant increasing or decreasing trend for the period 2012-2016, respectively.
Klebsiella pneumoniae: % of invasive isolates with combined resistance to carbapenems and colistin, EU/EEA, 2016 2016 Source: EARS-Net, 2017 All isolates tested for carbapenem susceptibility were included in the denominator to limit the effect of sequential testing.
Pandrug-resistant infections: an hypothetical challenge for Europe? Istockphoto
Outbreak of pandrug-resistant VIM-1 Providencia stuartii, Sept.-Nov. 2011 Source: Douka E, et al. Int J Antimicrob Agents 2015;48:533-6.
Examples Mycobacterium chimaera cardiovascular infections linked to heater-cooler devices Candida auris infection optra (transferable oxazolidinone and chloramphenicol resistance)
Modern medicine: not possible without effective antibiotics Hip / knee replacement Organ transplant Cancer chemotherapy Intensive care Care of preterm babies
Main actions to prevent and control antimicrobial resistance (AMR) New antimicrobial agents (with a novel mechanism of action, research, development) Prudent use of antimicrobial agents (only when needed, correct dose, correct dose intervals, correct duration) Infection prevention and control (hand hygiene, screening, isolation)
EU One Health Action Plan against Antimicrobial Resistance (29 June 2017) https://ec.europa.eu/health/amr/action_eu_en
EU Guidelines for the prudent use of antimicrobials in human health (June 2017) https://ec.europa.eu/health/amr/action_eu_en
Country visits to discuss antimicrobial resistance (AMR) issues, 2006-2017 As of 28 November 2017 Done Planned (invitation received) * Discussed Jointly with DG SANTE/F Based on Council Recommendation of 15 November 2001 on the prudent use of antimicrobial agents in human medicine (2002/77/EC) Reports (observations, conclusions, suggestions, examples of best practice) 23 EU Member States and 1 EU enlargement country (see map) 5 follow-up visits (Greece 2 and Hungary 2, Malta) 2018: 6 visits * jointly with DG SANTE/F5, in a One Health perspective Source: ECDC, 2017. ** *
ECDC rapid risk assessments http://ecdc.europa.eu/en/publications/risk_assessment/pages/default.aspx?p=2
https://ecdc.europa.eu/en/publications-data/directory-online-resources-prevention-and-control-antimicrobialresistance-amr
Source: ECDC, 2015. http://www.ecdc.europa.eu/en/healthtopics/healthcare-associated_infections/guidance-infection-preventioncontrol/pages/guidance-prevention-control-infections-caused-by-multidrug-resistant-bacteria-and-healthcare-associated-infections.aspx
Infection prevention and control measures and tools to prevent entry of carbapenem-resistant Enterobacteriaceae (CRE) into healthcare settings: ECDC guidance Core measures Profile for at risk patients who require supplemental measures Preliminary supplemental measures (at admission, for at risk patients) Supplemental measures (for confirmed CRE-positive patients) Source: Magiorakos et al. Antimicrob Resist Infect Control (15 November 2017).
https://antibiotic.ecdc.europa.eu
https://antibiotic.ecdc.europa.eu
A forward look into 2018 Burden of antimicrobial resistance (AMR) for the EU/EEA (Q2 2018) Annual update on AMR and antimicrobial consumption in humans in the EU/EEA (November 2018) ECDC point prevalence surveys of HAIs, AMR and antimicrobial use in European acute care hospitals and in long-term care facilities, 2016-2017 (ECDC publications, November 2018) Launch of project on whole genome sequencing (WGS)-based surveillance of carbapenem- and/or colistin-resistant Enterobacteriaceae (EURGen-Net)
18 November 2017 EU event, Brussels, 15 November 2017 E-mail: EAAD@ecdc.europa.eu Website: http://antibiotic.ecdc.europa.eu Facebook: EAAD.EU Twitter: @EAAD_EU (#EAAD) Global Twitter: #AntibioticResistance 13-19 NOVEMBER 2017