Hotspots of antimicrobial resistance in human & veterinary medicine

Transcription

1 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* Rue Juliette Wytsmanstraat Brussels Belgium T F nsih@wiv-isp.be

2 One Health

3 Carbapenem-resistant Causal relationship antibiotic consumption & resistance Pseudomonas aeruginosa (%) Carbapenem use (DDDs) Intervention programmes (AST) Lepper PM et al., 2002 (Germany)

4 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)

5 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

6 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 Acute hospital ,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 Ambulant (FARM) ,91 0,73-1,14 0,425 In hospital (HOSP) ,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 ,63 1,23 2,16 0, ,32 3,32 5,63 <0,001

7 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: The Author Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please journals.permissions@oup.com

8 Monthly consumption of ABHR solution. Lafaurie M et al. J. Antimicrob. Chemother. 2012;67: The Author Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please journals.permissions@oup.com

9 Change in monthly FQ-resistant P. aeruginosa rates, from 2002 to Lafaurie M et al. J. Antimicrob. Chemother. 2012;67: The Author Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please journals.permissions@oup.com

10 Change in monthly MRSA rates, from 2002 to Lafaurie M et al. J. Antimicrob. Chemother. 2012;67: The Author Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please journals.permissions@oup.com

11 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.

12 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

13 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

14 Point prevalence survey: PPS (photo) Surveillance contineously (film) &

15 Surveillances Gram - MRSA FEEDBACK C. difficile & ABU Campagnes Septicémies USI & ISO Indicateurs Rectangle = mandatory

16 Annual N casulties 2000 in 2008 ( in 2012 (bivv.be) Nosocomial infections: 6250 in 2007 (KCE 92A)

17 MRSA evolution

18 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

19 Carbapenemase producing enterobacteriaceae SHC, 2012

20 Global evolution of hand hygiene compliance 4th campaign preliminary results!

21 Compliance HH (%) Fourth Handhygiene campagne nurse MD Graphs by hhfct Rolemodel physicians!new module: January

22 Point prevalence survey: PPS (photo) Surveillance contineously (film) &

23 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

24 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

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27 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

28 DATA MANAGEMENT Upload Tarification Units ljst TUC codes Feedback molecules expressed as DDD (Defined Daily Dose) use (TUC) / Factor = use (DDD)

29 Example use (TUC) / Factor = use (DDD) Example : amoxicillin TUC Label ATC code Use (TUC) DDD Factor Use (DDD) AMOXICILLINE TEVA CAPS 1 X 500 MG J01CA04 40 units AMOXICILLINE TEVA SIR 1 X 250MG/5ML J01CA04 20 units

30 REALTIME FEEDBACK

31 FEEDBACK Compare own use with national mean

32 AUTOMATIC FEEDBACK Local follow up

33 FEEDBACK

34 OBJECTIVES MODULE Hospitals realtime feedback Automatic recalculation (TUC DDD) Local monitoring information for ABMT Authorities trend monitoring

35 DDD/1000 admissions DDD/1000 hospitalisation days J01: ANTIBACTERIALS FOR SYSTEMIC USE DDD/1000 patient days Antibacterials for Systemic Use (JO1) National mean median (p50) DDD/1000 admissions Antibacterials for Systemic Use (J01) National mean median (p50)

36 Graph 1 - Total AMD use ALL antimicrobials (DDD/1000 beddays), J01 + J02 + J04A + A07A + P01AB + D01B p

37 Graph 1 use ANTIBACTERIALs (DDD/1000 beddays), ANTIBACTERIALS FOR SYSTEMIC USE J01 J p

38 Non Pediatric Wards

39 Stratified by ward: antibacterials

40 Stratified by ward: antimycotics

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43 ESAC National level, all antimicrobials included HOSPITALS Year Participants Total DDD for the year DDD/1000 Nights * *: The data collection for the year 2011* is on-going.

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45 Community

46 Hospitals

47 Evolution - long term

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49 Point prevalence survey: PPS (photo) Surveillance contineously (film) &

50 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

51 % 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 Courtesy UA

52 Prevalence of AM use by Hospital average % 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% % on AM 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Mean: 38% [2% 100%] Net: 35% Courtesy UA

53 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%

54 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 % ( ) % % % % Surgical site infections (e) % ( ) % Urinary tract infections % ( ) % % % % Bloodstream infections % ( ) % % % % (BSI) (f) Gastro-intestinal system % ( ) % % % % infections Skin and soft tissue infections % ( ) % % % % Bone and joint infections % ( ) % % % % Eye, Ear, Nose or Mouth % ( ) % % % % infection Systemic infections (f) % ( ) % % % % Cardiovascular system infections Central nervous system infections Catheter-related infections w/o BSI (e) % ( ) % % % % % ( ) % % % % % ( ) % Reproductive tract infections % ( ) % % % % Missing/Unknown NA % % % Total % ( ) % % % % Zarb et al., 2012 Eurosurveillance

55 Point Prevalence Survey: Hai - ABU N pts (a) Prevalence% (95%CI) (b) N HAI (c) Relative % HAI (d) Pneumonia & other LRTI % ( ) % Surgical site infections (e) % ( ) % Urinary tract infections % ( ) % Bloodstream infections (BSI) (f) % ( ) % Gastro-intestinal system infections % ( ) % Skin and soft tissue infections % ( ) % Bone and joint infections % ( ) % Eye, Ear, Nose or Mouth infection % ( ) % Systemic infections (f) % ( ) % Zarb et al., 2012 Eurosurveillance

56 Les infections liées aux soins et la consommation d antimicrobiens dans les institutions de soins chroniques belges (projet HALT, 2010) Rue Juliette Wytsmanstraat Brussels Belgium T F info@wiv-isp.be

57 Résultats: Nursing homes 722 LTCF de 25 pays européens 111 établissements belges 107 MRS 3 institutions Sp 1 institution de psychiatrie chronique résidents éligibles Eligible residents: < > 5000 Courtesy: K. Latour

58 Résultats: caractéristiques des résidents 50% 85+ ans 25.7% masculin % 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

59 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

60 Résultats: la consommation d antimicrobiens 68.5% prescriptions thérapeutiques 31.5% prescriptions prophylactiques 48.7% 31.8% 10.8%

61 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

62 Courtesy: Jans B. & Latour K.

63 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

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65 One Health

66 MRSA evolution

67 Evolution of MRSA-incidence upon admission n. hôpitaux Vandendriessche et al, 2012

68 QUIZ: Prevalence Livestock associated MRSA

69 Livestock-associated MRSA Veal calves farmer a 72% LA-MRSA Swine farmer 38% LA-MRSA Inpatient hospital % 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

70 MRSA ST398 (infection + screening) Courtesy: Vandendriessche S ReferentieLaboratorium voor Stafylokokken - MRSA

71 Swine farms density Ribbens, Prev Vet Med 2009

72 Veal calves density Courtesy: Vandendriessche S E. Ducheyne and B. Pardon, 2012

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74 Treatment incidence on UDD (animals/1000 daily treaed) Consumption patterns across animal species 600 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., under revision Pardon et al., 2012 Courtesy: B. Pardon 76

75 Percentage of veal cohorts Indications and timing respiratory disease arrival prophylaxis diarrhea dysbacteriosis enterotoxaemia idiopathic peritonitis Weeks on feed BRD (53%) Arrival prophylaxis (13%), diarrhea (12%), dysbacteriosis (12%) Pardon ea, JAC 2012

76 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 TIUDD per 1000 animals Oxytetracycline (23,7%), amoxicillin (18,5%), tylosin (17,2%) and colistin (15,2%) were most frequently used

77 Resistentieprofiel LA-MRSA Co-selectie van resistentie 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

78 Possible outcomes of exposure to resistant bacteria P.L. Geenen, M.G.J. Koene, H. Blaak, A.H. Havelaar, A.W. van de Giessen

79 Bacteria & Co-selection of Resistance

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

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

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

83 Among European countries 2010: Belgium is the 3rd highest consumer of antimicrobials in veterinary medicine.

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85 Comparison Oral (Feed) vs Injection Checkley e.a., CVJ / VOL 51 / AUGUST 2010

86 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) II (10) III (10) Beef I (10) II (9) Veal T1 (5) T2 (5) > 25% Catry et al., 2008 National Report

87 Vulnerable populations Veterinary Co-selection = accumulation persistence

88 Dense communities = hotspots for AB & ABR FISH TO BE ADDED

89 Acknowledgements (ABU, ESAC) Dr. Stien Vandendriessche (LA-MRSA) Drs. Katrien Latour (HALT) Mevr. Beatrice Jans (MRSA, ESBL, CPE, HALT) Participating hospitals Slides available on: