RESISTANCE TO ANTIBIOTICS IN BELGIUM. AMR Policy Dialogue November 22, 2018

RESISTANCE TO ANTIBIOTICS IN BELGIUM AMR Policy Dialogue November 22, 2018 Boudewijn Catry Service Healthcare-associated infections and antimicrobial resistance

Point prevalence survey: PPS (photo) Surveillance continue (film) &

Conclusion on Pictures Healthcare associated infections (HAI) prevalence (%) in Belgium Hospitals: 7.3 (2017) Long term care facilities (LTCFs): 3.5 (2016) Estimated number of patients per year with an HAI in Belgium Hospital: 111 276 LTCFs: 170 090 Disability adjusted lifye years (DALY) calculations: Throughout Europe, this study concluded that an estimated number of 33 000 casualties are annually attributed to antimicrobial resistance. For Belgium, this number has been estimated at 530 deaths annually. Among these, 240 and 70 could be attributed to third-generation cephalosporin resistant Escherichia coli and Klebsiella pneumoniae (excluding those resistant to colistin and/or carbapenem), respectively, and 133 to MRSA (methicillin resistant Staphylococcus aureus). Further actions should focus on a reduction of inappropriate antimicrobial consumption and adequate preventive measures including hand hygiene and other infection control policies. Latour Katrien & Eline Vandael Brecht Devleeschauwer

Surveillances Gram - MRSA FEEDBACK C. difficile & Campaigns BeH-SAC Blood stream infections ICU & SSI VRE Indicators Rectangle = mandatory

CB1 CB2 MULTIDRUG RESISTANT ORGANISMS Microorganism Resistance MRSA Staphylococcus aureus Met(h)icillin ESBL+ Enterobacteriaceae 3 de generation cephalosporins (E.coli / Klebsiella / ) CPE Enterobacteriaceae Carbapenems VRE Enterococcus faecalis/faecium Vancomycin MDR Pseudomonas/Acinetobacter Different classes CDIF Clostridium difficile Intrinsic (Anaërobic) Urgent inquiries* e.g. Candida auris, Mycobacterium chimaera Intrinsic antibacterial, and/or multi antifungal resistance *ECDC Latour Katrien

Slide 5 CB1 Catry, Boudewijn; 29/06/18 CB2 Catry, Boudewijn; 29/06/18

Skin (MRSA) versus Gut bacteria (ESBL, CPE), Belgium 1994-2017 8 Incidence of MRSA and ESBL+ and CPE+ E. coli & K. pneumoniae per 1000 admissions (Belgian acute care hospitals; clinical samples only) 1994-2017 8 7 6 5 4 3 2 1 7 6 5 4 3 2 1 ESBL+ and CPE+ E. coli et K. pneumoniae /1000 admissions 0 0 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 ESBL+ Escherichia coli ESBL+ Klebsiella pneumoniae #REF! CPE+ Klebsiella pneumoniae MRSA Timely feedback is needed, also for outbreak support team (OST) Katrien Latour & Béatrice Jans MRSA: methicillin resistant Staphylococcus aureus; ESBL: extended spectrum beta-lactamase CPE: carbapenemase producing

EARS-net Belgium, S. aureus, E. coli, E. faecium blood, evolution of multiple resistance, 2013-2017 Mertens, K in press

EARS-net Belgium, E. coli (Urine vs Blood) Mertens, K in press

Remarkable findings 2017 Earsnet-Belgium Blood/CSF* *Preliminary results validation by NRC s ongoing S. aureus: decline MRSA: 8.7%IR in 2017 (versus 12.2%IR in 2016) E. coli: no increase in multi-resistance K. pneumoniae: no further increase R% for 3GC and carbapenems E. faecium: rise in resistance% vancomycin (5.5%R versus 1.7%R in 2016), teicoplanine (6.5%R versus 1.2%R in 2016) and linezolid (2.4%R versus 0.5%R in 2016) Thomas Struyf Karl Mertens

Surveillances Gram - MRSA FEEDBACK C. difficile & Campaigns BeH-SAC Blood stream infections ICU & SSI VRE Indicators Rectangle = mandatory

Clostridium difficile mean incidence per 1000 admissions (BE 2008-2017) Incidence moyenne des infections à C. difficile (ICD) dans les hôpitaux aigus, [Belgique 2008-2017] N/1000 admissions 2.00 1.50 1.00 0.50 1.75 1 0.00 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 ICD associés à l'hopital Total des ICD NOTE: - ICD associées à l hôpital: début des symptômes 2 jours après l admission - Calcul de l incidence: Inclusion de tous les hôpitaux ayant fourni des données complètes (numérateurs et dénominateurs) au moins 1 semestre/an Mortgat ea., in press

Clostridium difficile (CDIF), stratified by province (BE, 2017) Incidence moyenne des infections à C. difficiles (ICD) dans les hôpitaux aigus, par province [N/10.000 journées d hospitalisation, Belgique 2017] Mortgat ea., in press Note: Incidence moyenne de tous les hôpitaux aigus ayant participé à au moins 1 semestre. Les chiffres pour chaque province indiquent le nombre d hôpitaux-semestres. Les catégories (couleurs) pour l incidence sont basées sur les quartiles de la distribution.

Relationship Infuenza like illnes antimicrobial consumption - CDIF Figuur 1Non-pediatric antimicrobial use in the community in Daily Defined Doses per 1000 inhabitant days. Belgium 2007-2013 Bruyndonckx et al., submitted

Surveillance & notification Outbreak SCIENSANO Reference lab Outbreak support Competent authorities experts Elisabeth Miller & Hélène De Pauw

Enkele gegevens Enterobacteriaceae Enterobacteriaceae Enterobacteriaceae Enterobacteriaceae Miller E, De Pauw H

Compliance hand hygiene De Pauw H, Benhammadi N, et al. 2018

Compliance stratified by indication De Pauw H, Benhammadi N, et al. 2018

Compliance HH before sterile or invasive contact De Pauw H, Benhammadi N, et al. 2018

Compliance Hand hygiene in ICU BE (Fonguh et al. Archives Public Health 2016)

Ventilator associated pneumonia, ICU BE 1997-2015 Pneumonien per 1000 patient/intubatie dagen 0 5 10 15 20 25 30 35 IZ verworven Intubatie geassocieerd Intubatie gebruik 0 100 200 300 400 500 600 700 Intubatie dagen /1000 patient dagen Mertens K, WIV-ISP 2017 97 99 01 03 05 07 09 11 13 15 Jaar Figuur 2: Evolutie van IZ-verworven en intubatie geassocieerde pneumoniën, en intubatie gebruik op Intensieve Zorgen, NSIH-ICU surveillance België, 1997-2015. Mertens, 2017 WIV-ISP

Blood stream infections (BSI) Figure 10: Variation hospital-associated bloodstream infections between hospitals, Belgium 2017 (HABSI, hospital-associated bloodstream infection; SD, standard deviation) Duysburgh, E. 2018

Recoded Pneumonia & Sepsis for the sake of economic benefits

Surveillance & notification Outbreak SCIENSANO Reference lab Outbreak support Competent authorities experts Elisabeth Miller & Hélène De Pauw

https://www.healthstat.be

Evolution of the consumption* of antibacterials for systemic use (J01) in acute-care Belgian hospitals, 2003-2016 RIZIV/INAMI & Healthdata Vandael Eline et al., in prep. Currently 18 months delay realtime monitoring is asked *Expressed in defined daily doses (DDDs)/1000 patient days (2003-2016)

Anticaterial use (J01) stratified by type of hospitals

Stratification BSI by hospital type Duysburgh E. 2018

Blood stream infections stratified by region Duysburgh E. 2018

Evolution of the consumption* of antibacterials for systemic use (J01) in acute-care Belgian hospitals, 2003-2016 RIZIV/INAMI & Healthdata Vandael Eline et al., in prep. *Expressed in defined daily doses (DDDs)/1000 patient days (2003-2016)

Antibacterial consumption Belgium, 2017 Antibacterials for systemic use (ATC group J01) Consumption of antibacterials for systemic use (ATC group J01) in the community (primary care sector) and the hospital sector expressed in DDD per 1000 inhabitants and per day in 2017 ATC group J01 Community (primary care sector) Hospital sector Beta-lactam antibacterials, penicillins (J01C) 14.48 0.97 Other beta-lactam antibacterials (J01D) 1.17 0.40 Tetracyclines (J01A) 1.92 0.02 Macrolides, lincosamides and streptogramins (J01F) 3.41 0.11 Quinolone antibacterials (J01M) 2.17 0.19 Sulfonamides and trimethoprim (J01E) 0.19 0.04 Other J01 substances 2.55 0.16 Total 25.89 1.89

EARS-net Belgium Mertens, K in press

Consumption per animal species (DDD/1000 individual per day) Treatment incidence on UDD (animals/1000 daily treaed) 600 500 400 300 200 100 0 Antimicrobial use in livestock in Belgium poultry pigs dairy cattle beef cattle veal calves Persoons et al., 2012 Callens et al., 2012 Catry et al., 2016 Pardon et al., 2012 Courtesy: B. Pardon, UGent 32

BelVetSac.ugent.be

Results prevalence 2011-2017: Descriptive Statistics Resistance >50% 2011-2017 Ampicillin, Tetracycline, Sulphamethoxazole Trimethoprim 100 90 Resistance strains prevalence Veal calves - E. coli Ampicillin 80 70 Sulphamethoxazole Resistance (%) 60 50 40 Tetracycline 30 20 Trimethoprim 10 0 2011 2012 2013 2014 2015 2016 2017 Years

Results prevalence 2011-2017: Descriptive Statistics Sulphamethoxazole: 22,50 % (2017) 100 Resistance strains prevalence Beef cattle - E. coli Ampicillin 90 80 Chloramphenicol 70 Gentamicin Resistance (%) 60 50 40 30 Nalidixic acid Sulphamethoxazole 20 10 0 2011 2012 2013 2014 2015 2016 2017 Years Tetracycline Trimethoprim

N E. coli = >27 000; 5808; 812 (2005-2015)

Campylobacter jejuni in Poultry Meat (2017) % Sensible stable Co-R to CipNalTet (2 AB families) remains high and stable

Salmonella Porcine meat(pri 031) EU-AMR Project EU AMR Autocontrole n 46 EU AMR Gembloux 17 EU AMR Melle 38 Total 101 Famille d AB n % sensible 24 26.37 1 10 10.99 2 6 6.59 3 51 56.04

Antimicrobial consumption (J01) per animal species Treatment incidence on UDD (animals/1000 daily treaed) 600 500 400 300 200 100 0 Antimicrobial use in livestock in Belgium poultry pigs dairy cattle beef cattle veal calves Persoons et al., 2012 Callens et al., 2012 Catry et al., 2016 Pardon et al., 2012 Courtesy: B. Pardon, UGent 41

Anticaterial use (J01) stratified by type of hospitals Vandael et al, 2018

EARS-net Belgium Mertens, K in press

Antimicrobial consumption (J01) per animal species Treatment incidence on UDD (animals/1000 daily treaed) 600 500 400 300 200 100 0 Antimicrobial use in livestock in Belgium poultry pigs dairy cattle beef cattle veal calves Persoons et al., 2012 Callens et al., 2012 Catry et al., 2016 Pardon et al., 2012 Courtesy: B. Pardon, UGent 44

Antibacterial use Belgium, Intensive care vs hospital wide Vandael et al., 2018

Antimicrobial consumption (J01) per animal species Treatment incidence on UDD (animals/1000 daily treaed) 600 500 400 300 200 100 0 Antimicrobial use in livestock in Belgium poultry pigs dairy cattle beef cattle veal calves Persoons et al., 2012 Callens et al., 2012 Catry et al., 2016 Pardon et al., 2012 Courtesy: B. Pardon, UGent 46

Antibacterial consumption Belgium, 2017 Antibacterials for systemic use (ATC group J01) Consumption of antibacterials for systemic use (ATC group J01) in the community (primary care sector) and the hospital sector expressed in DDD per 1000 inhabitants and per day in 2017 ATC group J01 Community (primary care sector) Hospital sector Beta-lactam antibacterials, penicillins (J01C) 14.48 0.97 Other beta-lactam antibacterials (J01D) 1.17 0.40 Tetracyclines (J01A) 1.92 0.02 Macrolides, lincosamides and streptogramins (J01F) 3.41 0.11 Quinolone antibacterials (J01M) 2.17 0.19 Sulfonamides and trimethoprim (J01E) 0.19 0.04 Other J01 substances 2.55 0.16 Total 25.89 1.89 577,1 (2016)

Concluding remarks Focus on hospital consumption, stratified by type of hospitals Reflection in tertiary hospitals is urgently needed, in particular ICU (e.g. Guidelines vs Systematic reviews) Do no limit focus on acquired multidrug resistance (HAI at large, CDIF, ILI, mycoses, adverse events.) - Hand hygiene campaigns should be further elaborated Requirements: realtime feedback AM consumption = Prerequisite for containment during outbreaks (Outbreak support team) - allows also rapid evaluation of (inter)national intervention strategies One health: direct contact with animals has been underestimated for years Future deliverable: AM & AMR geographical mapping, stratified and open data

Acute care hospitals, AB consumption Vandael et al., 2018

Acknowledgements: The NSIH team, BAPCOC, NRCs the labs & hospitals & nursing homes & healthcare workers Boudewijn.Catry@sciensano.be