ECDC-EMEA Joint Technical Report Part I: Trends and burden of antimicrobial resistance in the European Union Zsuzsanna Jakab, Director European Centre for Disease Prevention and Control Jönköping, 6 July 2009

General background Prevention and control of AMR can be achieved by: Antimicrobial resistance (AMR) is still a growing European and global health problem. (Council Conclusions on Antimicrobial Resistance (AMR), Luxembourg, 10 June 2008) Prevention and control of AMR can be achieved by: Prudent use of existing of antimicrobial agents Good hygiene practices (infection control) Novel antimicrobial agents active on resistant bacteria Need to ascertain the perceived gap between: infections due to resistant bacteria development of novel agents aimed at treating such infections

Background for ECDC-EMEA Joint Report ECDC-EMEA Joint Working Group (established February 2008) Mandate To produce a report on “the gap between the increasing prevalence of multidrug-resistant bacteria and antibacterial drug development aimed at treating such infections” Composition ECDC appointed experts EMEA appointed experts ECDC and EMEA staff Co-opted experts, e.g. from ReAct Observers: European Commission, ESCMID

Methods (1): Selected resistant bacteria of public health importance Based on the most frequent bacteria responsible for bloodstream infections Certain resistances were used as indicators for multidrug resistance (resistance to multiple antibiotics) 6 most frequent resistant bacteria: Gram-positive-bacteria Methicillin-resistant Staphylococcus aureus (MRSA) Vancomycin-resistant Enterococcus faecium (VRE) Penicillin-resistant Streptococcus pneumoniae Gram-negative bacteria Third-generation cephalosporin-resistant Escherichia coli Third-generation cephalosporin-resistant Klebsiella pneumoniae Carbapenem-resistant Pseudomonas aeruginosa Source: EARSS & Biedenbach DJ et al., 2004.

Methods (2): Trends and burden of human infections due to resistant bacteria Data on resistant bacteria from bloodstream infections (European Antimicrobial Resistance Surveillance System - EARSS) 2002-2007 Human burden Extrapolations for 4 main types of infection (bloodstream, respiratory tract, skin and soft tissue, urinary tract) Extrapolations of burden parameters from published literature (e.g.: attributable mortality, extra length of stay in hospital) Economic burden Extra in-hospital costs Productivity losses due to absence from work because of illness and premature death of infected patients

Percentage of resistant isolates in bacteria from bloodstream infections, EU countries, Iceland and Norway, 2007 Country with a significant increase (2005-2007)  Country with a significant decrease (2005-2007) Methicillin-resistant S. aureus - MRSA (%) No. of countries 3rd-gen. ceph.-resistant Escherichia coli (%) 3rd-gen. ceph.-resistant Klebsiella pneumoniae (%) Source: EARSS & ECDC, 2009

Population-weighted, average %resistant isolates among bacteria from bloodstream infections, EU, Iceland and Norway, 2002-2007 Gram-positive bacteria Gram-negative bacteria *Excluding Greece, which did not report data. **Excluding Belgium and Slovakia, which did not report data. Source: EARSS & ECDC, 2009

Burden of multidrug-resistant (MDR) bacteria in the EU, Iceland and Norway Human burden Economic burden Limitation: these are underestimates. Infections (6 most frequent MDR bacteria, 4 main types of infection) approx. 400,000 / year Attributable deaths approx. 25,000 / year Extra hospital days approx. 2.5 million / year Extra in-hospital costs approx. € 1 billion / year Productivity losses approx. € 600 million / year Source: ECDC, 2009

Conclusions Resistance to antibiotics is high in bacteria that cause serious infections in humans. Resistance is increasing among certain bacteria (i.e., Gram-negative bacteria). Infections caused by multidrug-resistant bacteria are associated with excess morbidity and mortality. These infections are associated with substantial extra costs.