Hotspots of antimicrobial resistance in human & veterinary medicine Anne Ingenbleek Mat Goossens Natacha Viseur Sylvanus Fonguh Naima Hammami Marie-Laurence Lambert Karl Mertens Katrien Latour Béatrice Jans Boudewijn Catry* www.nsih.be Rue Juliette Wytsmanstraat 14 1050 Brussels Belgium T +32 2 642 51 11 F +32 2 642 54 10 email: nsih@wiv-isp.be http://www.nsih.be
One Health
Carbapenem-resistant Causal relationship antibiotic consumption & resistance Pseudomonas aeruginosa (%) Carbapenem use (DDDs) Intervention programmes (AST) 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: journals.permissions@oup.com
Monthly consumption of ABHR solution. 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: journals.permissions@oup.com
Change in monthly FQ-resistant P. aeruginosa rates, from 2002 to 2010. 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: journals.permissions@oup.com
Change in monthly MRSA rates, from 2002 to 2010. 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: journals.permissions@oup.com
Mission 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.
SURVEILLANCE (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
SURVEILLANCE (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 Gram - MRSA FEEDBACK C. difficile & ABU Campagnes Septicémies USI & ISO Indicateurs Rectangle = mandatory
Annual N casulties 2000 in 2008 (www.wiv-isp.be) +850 in 2012 (bivv.be) Nosocomial infections: 6250 in 2007 (KCE 92A)
MRSA evolution
Communautaire 14,4% Contacts inconnus 9,3% 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!
Compliance HH (%).2.4.6.8 1 Fourth Handhygiene campagne nurse MD Graphs by hhfct Rolemodel physicians!new module: January 11 2013 www.nsih.be
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 J01C J01D J01M J01X J02A J01F J01G J04A J01E A07A P01A J01A3 D01B J01B0 Class Beta-lactam antibacterials, penicillins Other beta-lactam antibacterials Quinolone antibacterials Other antibacterials Antimycotics for systemic use Macrolides, lincosamides and streptogramins Aminoglycoside antibacterials Drugs for treatment of tuberculosis Sulfonamides and trimethoprim Intestinal anti-infectives Agents against amoebiasis/protozoal diseases Tetracyclines Antifungals for systemic use 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 ( 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 Tarification Units ljst TUC codes Feedback molecules expressed as DDD (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 CAPS 1 X 500 MG J01CA04 40 units 1000 2 20 744433 AMOXICILLINE TEVA SIR 1 X 250MG/5ML J01CA04 20 units 1000 4 5
REALTIME FEEDBACK
FEEDBACK Compare own use with national mean
AUTOMATIC FEEDBACK Local follow up
FEEDBACK
OBJECTIVES MODULE Hospitals realtime feedback Automatic recalculation (TUC DDD) Local monitoring information for ABMT Authorities trend monitoring
DDD/1000 admissions DDD/1000 hospitalisation days J01: ANTIBACTERIALS FOR SYSTEMIC USE DDD/1000 patient days Antibacterials for Systemic Use (JO1) 700 600 500 400 300 National mean median (p50) 200 100 0 2006 2007 2008 2009 2010 DDD/1000 admissions Antibacterials for Systemic Use (J01) 6000 5000 4000 3000 2000 National mean median (p50) 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 short measuring period less labor intensive What is measured? AB use Hai Result: estimate the total burden describe patients invasive procedures infections antimicrobials prescribed
11 13 15 20 38 59 58 34 27 63 49 30 50 2 62 14 51 61 40 37 7 48 55 41 16 18 17 46 33 24 57 21 12 36 56 19 39 43 605 26 31 9 25 10 % patients with HAI Point Prevalence Survey: Hai - ABU Percentage patients with HAI: 7.0% 25% 20% 15% 10% Mean prevalence: 7% [0%-23%] 5% 0% Hospital number 53 22 42 4 29 45 23 28 32 44 52 35 6 54 8 47 3 1 Courtesy UA
Prevalence of AM use by Hospital 10 17 447 19 208 136 60 284 23 1895 21 11 59 25 45 26 43 47 16 34 36 average 61 52 54 39 32 40 46 49 35 42 41 24 33 581 37 27 56 622 63 29 50 51 48 53 57 31 55 14 38 30 15 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% % on AM 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 12 3 22 Mean: 38% [2% 100%] Net: 35% Courtesy UA
Point Prevalence Survey: Hai - ABU On antimicrobials: 36.6% Mean antimicrobials for those on antimicrobials: 1.5 Indication for Antimicrobial N=5543 1% 44% 13% 4% 15% 4% 3% 8% HI CI LI M U S1 S2 S3 :acute hospital-acquire :community-acquired :acquired in NH :medical prophylaxis :unknown reason :single dose :one day Surg :> 1 day 23%
Point Prevalence Survey: Hai - ABU Table 2. Healthcare associated infection (HAI) and antimicrobial use prevalence by site Healthcare-associated infection sites Indication for antimicrobial treatment N pts (a) Prevalence% (95%CI) (b) N HAI (c) Relative % HAI (d) Total Relative % use CI* % HI** % Pneumonia & other LRTI 392 2.0% (1.8-2.2) 394 25.7% 1328 29.2% 922 31.6% 382 24.8% Surgical site infections (e) 290 1.5% (1.3-1.6) 290 18.9% Urinary tract infections 263 1.3% (1.2-1.5) 264 17.2% 679 14.9% 412 14.1% 237 15.4% Bloodstream infections 216 1.1% (0.9-1.2) 217 14.2% 219 4.8% 67 2.3% 145 9.4% (BSI) (f) Gastro-intestinal system 118 0.6% (0.5-0.7) 119 7.8% 593 13.0% 466 16.0% 117 7.6% infections Skin and soft tissue infections 59 0.3% (0.2-0.4) 59 3.9% 646 14.2% 357 12.2% 279 18.1% Bone and joint infections 38 0.2% (0.1-0.3) 39 2.5% 154 3.4% 92 3.2% 60 3.9% Eye, Ear, Nose or Mouth 47 0.2% (0.2-0.3) 47 3.1% 211 4.6% 170 5.8% 41 2.7% infection Systemic infections (f) 40 0.2% (0.1-0.3) 40 2.6% 668 14.7% 318 10.9% 334 21.7% Cardiovascular system infections Central nervous system infections Catheter-related infections w/o BSI (e) 26 0.1% (0.1-0.2) 26 1.7% 76 1.7% 40 1.4% 36 2.3% 15 0.1% (0.0-0.1) 15 1.0% 67 1.5% 54 1.8% 12 0.8% 11 0.1% (0.0-0.1) 11 0.7% Reproductive tract infections 10 0.1% (0.0-0.1) 10 0.7% 65 1.4% 49 1.7% 16 1.0% Missing/Unknown NA 65 1.4% 39 1.3% 25 1.6% Total 1408 7.1% (6.7-7.5) 1531 100% 4552 100% 2919 100% 1539 100% Zarb et al., 2012 Eurosurveillance
Point Prevalence Survey: Hai - ABU N pts (a) Prevalence% (95%CI) (b) N HAI (c) Relative % HAI (d) Pneumonia & other LRTI 392 2.0% (1.8-2.2) 394 25.7% Surgical site infections (e) 290 1.5% (1.3-1.6) 290 18.9% Urinary tract infections 263 1.3% (1.2-1.5) 264 17.2% Bloodstream infections (BSI) (f) 216 1.1% (0.9-1.2) 217 14.2% Gastro-intestinal system infections 118 0.6% (0.5-0.7) 119 7.8% Skin and soft tissue infections 59 0.3% (0.2-0.4) 59 3.9% Bone and joint infections 38 0.2% (0.1-0.3) 39 2.5% Eye, Ear, Nose or Mouth infection 47 0.2% (0.2-0.3) 47 3.1% Systemic infections (f) 40 0.2% (0.1-0.3) 40 2.6% Zarb et al., 2012 Eurosurveillance
Les infections liées aux soins et la consommation d antimicrobiens dans les institutions de soins chroniques belges (projet HALT, 2010) Rue Juliette Wytsmanstraat 14 1050 Brussels Belgium T +32 2 642 51 11 F +32 2 642 50 01 email: info@wiv-isp.be www.wiv-isp.be
Résultats: Nursing homes 722 LTCF de 25 pays européens 111 établissements belges 107 MRS 3 institutions Sp 1 institution de psychiatrie chronique 12 727 résidents éligibles Eligible residents: < 250 250-499 500-999 1000-4999 > 5000 Courtesy: K. Latour
Résultats: caractéristiques des résidents 50% 85+ ans 25.7% masculin 100 80 60 40 20 0 59.0% 48.3% 41.1% 2.6% 0.2% 3.4% 8.1% Incontinence Désorientation Chaise roulanté ou alitée Cathéter urinaire Cathéter vasculaire Plaie d'escarre Autre plaie
Résultats: la consommation d antimicrobiens 554 résidents, 578 molécules Prévalence: 4.7% (0-15.7%) 96% antibactériens à usage systémique (classe ATC J01) 1 Aminoglycosid es (J01G) 0,4% Autres antibactériens (J01X) 36,9% Beta-lactam pen. (J01C) 27,9% 2 Tétracyclines (J01A) 2,3% Sulfamides (J01E) 3,2% Autres betalactams (J01D) 4,1% Macrolides (J01F) 4,7% Quinolones (J01M) 20,4% 3
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%) Infection respiratoire; 187; 48% 1 BSI; 2; 1% Infection GI; 21; Fièvre; 3; 1% 5% Infection urinaire; 36; 9% 4 Infection cutanée; 81; 21% Nez/gorge/oreil les/yeux; 39; 10% Autre infection; 21; 5% 3 2
Courtesy: Jans B. & Latour K.
Concluding remarks HUMAN 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
One Health
MRSA evolution
Evolution of MRSA-incidence upon admission 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 1 3 10 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
Treatment incidence on UDD (animals/1000 daily treaed) Consumption patterns across animal species 600 Antimicrobial use in livestock in Belgium 500 400 300 200 100 0 poultry pigs dairy cattle beef cattle veal calves Persoons et al., 2012 Callens et al., 2012 Catry et al., under revision Pardon et al., 2012 Courtesy: B. Pardon 76
Percentage of veal cohorts Indications and timing 100.0 90.0 80.0 70.0 60.0 50.0 40.0 respiratory disease arrival prophylaxis diarrhea dysbacteriosis enterotoxaemia idiopathic peritonitis 30.0 20.0 10.0 0.0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 Weeks on feed BRD (53%) Arrival prophylaxis (13%), diarrhea (12%), dysbacteriosis (12%) Pardon ea, JAC 2012
Classification of antimicrobials according to importance for human medicine Which compounds are used? Pardon ea, JAC 2012 enrofloxacin flumequine amoxycillin ampicillin I II tylosin tilmicosin oxytetracycline doxycyclin sulphonamides + trimethoprim colistin 0.00 20.00 40.00 60.00 80.00 100.00 120.00 140.00 160.00 TIUDD per 1000 animals Oxytetracycline (23,7%), amoxicillin (18,5%), tylosin (17,2%) and colistin (15,2%) were most frequently used
Resistentieprofiel LA-MRSA 100 80 Co-selectie van resistentie 60 40 20 0 Aminosides Macrolides, lincosamides Varken s Mensen 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 herds) N ARI a AMP b AMC CEF TET TMP NEO GEN SPT STR NAL FLU ENR 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
Vulnerable populations Veterinary Co-selection = accumulation persistence
Dense communities = hotspots for AB & ABR FISH TO BE ADDED
Acknowledgements Anne.Ingenbleek@wiv-isp.be (ABU, ESAC) Dr. Stien Vandendriessche (LA-MRSA) Drs. Katrien Latour (HALT) Mevr. Beatrice Jans (MRSA, ESBL, CPE, HALT) Participating hospitals nsih@wiv-isp.be Slides available on: www.nsih.be