Consumption of Antibiotics at the National Level

Consumption of antibiotics at the national level – human medicine

AnneAnne IngenbleekIngenbleek MatMat GoossensGoossens NatachaNatacha Viseur Viseur SylvanusSylvanus FonguhFonguh NaimaNaima Hammami Hammami Marie-LaurenceMarie-Laurence LambertLambert KarlKarl MertensMertens KatrienKatrien Latour Latour BéatriceBéatrice Jans Jans BoudewijnBoudewijn Catry*Catry* www.nsih.bewww.nsih.be

Intervention programmes (AST) (%) Carbapenem use (DDDs) Carbapenem-resistant Pseudomonas aeruginosa

Lepper PM et al., 2002 (Germany) Causal relationship inadequate therapy & mortality

The Influence of Inadequate Antimicrobial Treatment of Bloodstream Infections on Patient Outcomes in the ICU Setting* Ibrahim et al., Chest 2000, 118 (1) Risk factors for antibacterial resistance at the individual level: a multicentric study (IARG) Objective To demonstrate at the individual patient level associations between antibiotic (AB) consumption and antibacterial resistance • Infections & colonisation (Pathogens & commensals) • Dosis/response effect (Defined Daily Dose, WHO) • Adjusting for covariates

Evidence: aggregated population level Risk factors MRSA infection/colonisation multivariate analysis (n= 6844)

Variable Adjusted OR (95%CI) p-value MRSA positive related to type of health care setting No admission 1527 1 - Acute hospital 4647 0,86 0,74 1,01 0,069 Nursing home (LTCF) 560 3,53 2,79 4,46 <0,001 Other setting 110 1,43 0,93 2,19 0,102 AB consumption prior to sampling (prescription prior or on the day of sampling) Absent 1519 1 - Ambulant (FARM) 3706 0,91 0,73-1,14 0,425 In hospital (HOSP) 1619 1,62 1,30 2,01 <0,001 Amount of AB use prior to sampling per DDD 1,32 1,25 1,40 <0,001

Age category 0-14 757 1 - 15-54 1837 1,63 1,23 2,16 0,001 55-104 4250 4,32 3,32 5,63 <0,001

Monthly FQ consumption, expressed as DDD/1000 PD. Filled circles, pre-intervention period values; open circles, intervention period values; diamonds, post-intervention period values.

Lafaurie M et al. J. Antimicrob. Chemother. 2012;67:1010- 1015

© The Author 2012. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: [email protected] Monthly consumption of ABHR solution.

Lafaurie M et al. J. Antimicrob. Chemother. 2012;67:1010- 1015

To provide standardized definitions and tools for the containment of health care associated infections in hospitals and nursing homes, and to establish national reference data on incidence of nosocomial infections and antimicrobial resistance. SURVEILLANCESURVEILLANCE (1/2)(1/2)

Four Mandatory Surveillances in Acute Care Hospitals

1. Methicillin resistant Staphylococcus aureus 2. Clostridium difficile (optional: ribotyping) 3. Antimicrobial use in hospitals 4. One out of 4 optional surveillances: • Septicaemias hospital wide • Surgical site infections • Intensive care units • Extended spectrum beta-lactamases

In progress: quality indicators SURVEILLANCESURVEILLANCE (2/2)(2/2)

Volontary projects in Hospitals & Nursing homes

Hand hygiene campaigns (fifth in preparation, launch 2012) Point Prevalence survey on HCAI & AM MRSA, ESBL & VRE in Nursing homes (BAPCOC)

Other projects - Expertise

EARSS, ESAC, BelVet-SAC, ESVAC, PILGRIM… TATFAR, CODEX alimentarius (WHO/FAO/OIE) promotor Master Thesis, reviewing articles, parlementary questions Point prevalence survey: PPS (photo)

Surveillance contineously (film)

& Surveillances

FEEDBACK Gram - MRSA

& Campagnes C. difficile ABU

Septicémies USI & ISO Indicateurs

Rectangle = mandatory Jaarlijks aantal doden

2000 in 2008 944 in 2009 (www.wiv-isp.be) (bivv.be)

MRSA in ziekenhuizen: 6121 MRSA infecties in 2010 (www.nsih.be) Ongeveer 525 doden door nosocomiale MRSA infectie in 2007 Courtesy: S. Vandendriessche MRSA evolution Contacts inconnus 9,3% Communautaire 14,4% Portage connu 43,6%

Transfert d'un Hôpital et MR/MRS 6%

Transfert d'une MR/MRS 12,6% Transfert d'un hôpital 14,1%

Individual hospital/NH is client! Jans & Denis, 2011 Carbapenemase producing enterobacteriaceae

SHC, 2012 Global evolution of hand hygiene compliance

4th campaign preliminary results! Point prevalence survey: PPS (photo)

Surveillance contineously (film)

& Materials & methods

Specialities to be reported (WHO, ESAC, pubMED) ATC classification: A07A Antibiotics for gastro-intestinal use J01, P01AB Antibiotics J02, D01BA Antimycotics for systemic use J04A Tuberculostatics ATC Class J01C Beta-lactam antibacterials, penicillins J01D Other beta-lactam antibacterials J01M Quinolone antibacterials J01X Other antibacterials J02A Antimycotics for systemic use J01F Macrolides, lincosamides and streptogramins J01G Aminoglycoside antibacterials J04A Drugs for treatment of tuberculosis J01E Sulfonamides and trimethoprim A07A Intestinal anti-infectives P01A Agents against amoebiasis/protozoal diseases J01A3 Tetracyclines D01B Antifungals for systemic use J01B0 Amphenicols

Outils informatiques

SEP, SI (ICU), ISO (SSI), HH: NSIHwin (Application MS Access) CDIF, MRSA … ABU (déc 07)…: NSIHweb • => comparaison immédiate avec les données nationales • => mise à jour « automatique » • => input & upload des données (Ì charge de travail) • Données communes (dénominateurs/mois, charactéristiques des hôpitaux, services & unités) • Autres fonctions d’analyse etc (ex. détection des épidémies) à définir avec groupe de travail DATA MANAGEMENT

Upload Feedback • ‘molecules’ • ‘Tarification Units’ • expressed as DDD • ljst TUC codes (Defined Daily Dose)

use (TUC) / Factor = use (DDD) Example

use (TUC) / Factor = use (DDD)

Example : amoxicillin

TUC Label ATC code Use (TUC) DDD Factor Use (DDD) 744185 AMOXICILLINE TEVA J01CA04 40 units 1000 2 20 CAPS 1 X 500 MG

744433 AMOXICILLINE TEVA J01CA04 20 units 1000 4 5 SIR 1 X 250MG/5ML REALTIME FEEDBACK FEEDBACK Compare own use with national mean AUTOMATIC FEEDBACK Local follow up FEEDBACK OBJECTIVES MODULE

Hospitals • realtime feedback • Automatic recalculation (TUC Æ DDD) • Local monitoring Æ information for ABMT

Authorities • trend monitoring J01: ANTIBACTERIALS FOR SYSTEMIC USE DDD/1000 patient days

Antibacterials for Systemic Use (JO1)

700 600 500 400 National mean 300 median (p50) 200 100 DDD/1000 hospitalisation days hospitalisation DDD/1000 0 2006 2007 2008 2009 2010 DDD/1000 admissions

Antibacterials for Systemic Use (J01)

6000

5000

4000 National mean 3000 median (p50) 2000

DDD/1000 admissions 1000

0 2006 2007 2008 2009 2010 Graph 1 ‐ Total AMD use ALL antimicrobials (DDD/1000 beddays), 2006‐2010 J01 + J02 + J04A + A07A + P01AB + D01B

2006 2007 2008 2009 2010 p50 479 565 558 570 573 Graph 1 – use ANTIBACTERIALs (DDD/1000 beddays), 2006‐2010 ANTIBACTERIALS FOR SYSTEMIC USE J01

J01

2006 2007 2008 2009 2010

p50 467 527 530 545 537 Non Pediatric Wards Stratified by ward: antibacterials Stratified by ward: antimycotics

ESAC

National level, all antimicrobials included HOSPITALS

Year Participants Total DDD for the year DDD/1000 Nights 2008 121 7315319.20 579.734 2009 124 7273099.57 583.651 2010 120 6940067.65 585.087 2011* 106 6561559.15 581.215

2011*: The data collection for the year 2011* is on‐going.

Community Hospitals Evolution - long term

Point prevalence survey: PPS (photo)

Surveillance contineously (film)

& Point Prevalence Survey: Hai - ABU

Why? - A need to standardize protocols in EU - Measuring prevalence, not incidence Æ short measuring period Æ less labor intensive

What is measured? AB use – Hai

Result:

• estimate the total burden

• describe patients

• invasive procedures

• infections

• antimicrobials prescribed Point Prevalence Survey: Hai - ABU

Percentage patients with HAI: 7.0%

25%

20%

15% Mean prevalence: 7% [0%-23%] 10%

% patients with HAI with patients % 5%

0% 2 7 5 4 6 8 3 1 9 11 13 15 20 38 59 58 34 27 63 49 30 50 62 14 51 61 40 37 48 55 41 16 18 17 46 33 24 57 21 12 36 56 19 39 43 60 53 22 42 29 45 23 28 32 44 52 35 54 47 26 31 25 10 Hospital number

Courtesy UA Prevalence of AM use by Hospital

100% 90% 80% 100% 70% 90% Mean: 38% [2% – 100%] 80% 60% Net: 35% 70% 50% 60% 40% 50%

40% 30% 30% 20% 20% 10% 10%

0% 0% 7 8 6 4 9 5 3 1 2 10 17 44 19 20 13 60 28 23 18 12 22 21 11 59 25 45 26 43 47 16 34 36 61 52 54 39 32 40 46 49 35 42 41 24 33 58 37 27 56 62 63 29 50 51 48 53 57 31 55 14 38 30 15 % on AM average

Courtesy UA Point Prevalence Survey: Hai - ABU On antimicrobials: 36.6% Mean antimicrobials for those on antimicrobials: 1.5

:acute hospital-acquire :community-acquired :acquired in NH :medical prophylaxis :unknown reason :single dose :one day Surg :> 1 day Les infections liées aux soins et la consommation d’antimicrobiens dans les institutions de soins chroniques belges (projet HALT, 2010)

• 722 LTCF de 25 pays européens

• 111 établissements belges Eligible residents: < 250 250 ‐ 499 • 107 MRS 500 ‐ 999 1000 ‐ 4999 • 3 institutions Sp > 5000 • 1 institution de psychiatrie chronique • 12 727 résidents éligibles

Courtesy: K. Latour Résultats: caractéristiques des résidents

50% 85+ ans 25.7% masculin

100 80 59.0% 48.3% 60 41.1% 40 20 8.1% 2.6% 0.2% 3.4% 0

ce on ée ire ire rre aie en tati lit na la ca pl tin n u a ri cu 'es tre on rie o r u as d u nc so té éte r v ie A I Dé lan th éte Pla ou Ca th e r Ca ais Ch Résultats: la consommation d’antimicrobiens

• 554 résidents, 578 molécules • Prévalence: 4.7% (0‐15.7%)

• 96% antibactériens àusage systémique (classe ATC J01) Tétracyclines Sulfamides Autres beta‐ Aminoglycosid (J01A) 2,3% (J01E) 3,2% lactams es (J01G) 0,4% (J01D) 4,1% 1 Autres Macrolides antibactériens (J01F) 4,7% (J01X) 36,9% Quinolones Beta‐lactam (J01M)3 20,4% pen. (J01C) 27,9% 2 Résultats: la consommation d’antimicrobiens

• 68.5% prescriptions thérapeutiques • 31.5% prescriptions prophylactiques

48.7% 31.8% 10.8% Résultats: les infections liées aux soins

•390 infections confirmées, 361 résidents •Prévalence: 3.1% (0‐11.9%)

4 Infection 1 urinaire; 36; 9% Infection 2 Infection cutanée; 81; respiratoire; 21% 187; 48% Nez/gorge/oreil les/yeux; 39; 3 10% Autre infection; BSI; 2; 1% Infection GI; 21; 21; 5% Fièvre; 3; 1% 5% Courtesy: Jans B. & Latour K. Concluding remarks

Within hospital evolution >> bench marking stratification: service (ICU), type, size, region Hospital evolution MRSA, MRE, Cdiff, HH compliance… can be combined - Monthly introductin required - Many have done this retrospectively!!! Future: evolution i.f.v. DRG (project AMTABU) - hip/knee replacement & CAP Nursing homes: less AB use profylaxis UTI can be improved Links

• NSIH web • https://nsihweb.wiv-isp.be . • Manual NSIHweb - AB • www.nsih.be > geneesmiddelen > download > handleiding voor de webapplicatie • List TUC codes • www.nsih.be > geneesmiddelen > download > geneesmiddelenregister • Protocol • www.nsih.be > geneesmiddelen > download > surveillanceprotocol Acknowledgements

[email protected] (ABU, ESAC) Dr. Stien Vandendriessche (LA-MRSA) Drs. Katrien Latour (HALT) Mevr. Beatrice Jans (MRSA, ESBL, CPE, HALT) Participating hospitals [email protected]

Slides available on: www.nsih.be

Consumption of antibiotics in veterinary medicine

BoudewijnBoudewijn Catry*Catry* AnneAnne IngenbleekIngenbleek BartBart PardonPardon StienStien VandendriesscheVandendriessche BeaBea JansJans www.nsih.bewww.nsih.be

n. hôpitaux 29 34 44 48 41 43

Vandendriessche et al, 2012 QUIZ: Prevalence Livestock associated MRSA Livestock-associated MRSA

Veal calves farmer a 72% LA-MRSA Swine farmer 38% LA-MRSA Inpatient hospital 1.6-25% MRSA Nursing home resident 13% MRSA Veterinarians 7.5% LA-MRSA Poultry farmers a 3% LA-MRSA Upon hospital admission 1.6% MRSA General population 0.5% MRSA

a Samples from non-mixed farms

Gordts, 2007 Denis, JAC 2010 Denis, EID 2009 Vandendriessche, JAC 2012 Garcia‐Graells, E&I 2011 Goossens et al., 2012 MRSA ST398 (infection + screening)

4 18 13 10 3 1

1 4

Courtesy: Vandendriessche S

ReferentieLaboratorium voor Stafylokokken ‐ MRSA Swine farms density

Ribbens, Prev Vet Med 2009 Veal calves density

Courtesy: Vandendriessche S

E. Ducheyne and B. Pardon, 2012

Consumption patterns across animal species

Persoons et al., 2012 Callens et al., 2012 Catry et al., under revision Pardon et al., 2012

Courtesy: B. Pardon 75 Indications and timing

BRD (53%) Arrival prophylaxis (13%), diarrhea (12%), dysbacteriosis (12%) Pardon ea, JAC 2012 Which compounds are used? Pardon ea, JAC 2012

Oxytetracycline (23,7%), amoxicillin (18,5%), tylosin (17,2%) and colistin (15,2%) were most frequently used Resistentieprofiel LA-MRSA

Co‐selectie van resistentie

Aminosides Macrolides, lincosamides MRSA huidinfecties bij de mens worden vaak behandeld met doxycycline of clindamycine Niet aangewezen voor LA-MRSA infecties

Vandendriessche, JAC 2012 Possible outcomes of exposure to resistant bacteria

P.L. Geenen, M.G.J. Koene, H. Blaak, A.H. Havelaar, A.W. van de Giessen Bacteria & Co-selection of Resistance Evolution E. coli multiresistance

P.L. Geenen, M.G.J. Koene, H. Blaak, A.H. Havelaar, A.W. van de Giessen Evolution E. coli multiresistance

Vaporization: ceftiofur P.L. Geenen, M.G.J. Koene, H. Blaak, A.H. Havelaar, A.W. van de Giessen Evolution E. coli multiresistance

P.L. Geenen, M.G.J. Koene, H. Blaak, A.H. Havelaar, A.W. van de Giessen Among European countries 2010: Belgium is the 3rd highest consumer of antimicrobials in veterinary medicine. www.BelVet-SAC.ugent.be www.BelVet-SAC.ugent.be Comparison Oral (Feed) vs Injection

Checkley e.a., CVJ / VOL 51 / AUGUST 2010 Resistance E. coli

Type period N ARIa AMP AMC CEF TET TMP NEO GEN SPT STR NAL FLU ENR (N b herds) Dairy I (10) 447 0.04 2.91 0.45 0.45 8.28 4.25 0.67 1.12 0.22 24.83 1.34 0.22 0 II (10) 396 0.01 2.02 0.25 0 3.79 0.25 1.52 0 0.25 4.55 0.76 0.25 0.25 III (10) 419 0.02 4.3 0.24 0 4.3 3.58 2.15 0.48 0 7.88 1.19 0.72 0.24

Beef I (10) 436 0.03 9.17 1.15 0 6.88 4.13 2.52 0.92 0.69 13.3 2.52 0.46 0.46 II (9) 346 0.06 12.14 1.45 0.58 17.05 5.49 4.91 2.31 0.87 18.21 8.67 4.33 2.89

Veal T1 (5) 276 0.62 93.12 4.71 0.36 94.93 92.75 83.33 45.29 22.46 89.49 79.00 73.13 64.23 T2 (5) 230 0.32 79.57 2.61 1.74 95.22 65.22 27.83 5.22 5.65 78.26 14.01 6.22 4.12

> 25%

Catry et al., 2008 National Report Dense communities = hotspots for AB & ABR Vulnerable populations

Co-selection = accumulation – persistence… Acknowledgements: S Vandendriessche, C Garcia, O Denis, B Jans, M Goossens, N Viseur, A Ingenbleek B. Pardon, B Callens, J Dewulf, F Haesebrouck the labs & hospitals & nursing homes & veterinarians

[email protected]@wiv-isp.be