«Antibiotic Stewardship» programmes & antibiotic resistance

Transcription

1 «Antibiotic Stewardship» programmes & antibiotic resistance Winfried V. Kern Abteilung Infektiologie Universitätsklinikum Freiburg

2 Agenda Definition Healthcare quality & patient safety aspects Research aspects

3 What is Antibiotic Stewardship? ongoing effort by a healthcare institution to optimize antimicrobial use among hospitalized patients to... - improve patient outcomes - ensure cost-effective therapy, and - reduce adverse sequelae of antimicrobial use (including antimicrobial resistance). MacDougall & Polk CMR 2005

4 What is Antibiotic Stewardship? system ongoing effort by a healthcare institution to optimize antimicrobial use among hospitalized patients to... - improve patient outcomes - ensure cost-effective therapy, and - reduce adverse sequelae of antimicrobial use (including antimicrobial resistance). MacDougall & Polk CMR 2005

5 The development of new antibiotics without having mechanisms to ensure their appropriate use is much like supplying your alcoholic patients with a finer brandy. Dennis Maki 1998

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7 assumptions prescribing is (often) suboptimal

8 assumptions prescribing is (often) suboptimal (and often too excessive)

9 assumptions prescribing is (often) suboptimal (and often too excessive) and induces resistance

10 assumptions prescribing is (often) suboptimal (and often too excessive) and reduces resistance optimized (and/or reduced) prescribing improves outcomes and can minimize or even reverse antimicrobial resistance

11 Bratzler et al Arch Surg 2005

12 European data (ESAC-PPS 2006*) *20 hospitals, 11,571 patients, 30% with antibiotics Ansari et al CID 2009

13 European data (ESAC-PPS 2008*) *50 hospitals, 28 countries ESAC investigators 2011

14 European data (ESAC-PPS 2010*) surgical prophylaxis exceeded one day in 61% of cases *66 hospitals, 23 countries Zarb et al Eurosurv 2012

15 Burden of hospital-wide inadequate antibiotic prescriptions 9% n=776 Turkey % n=107 France % n=104 France % n=1079 UK % n=2306 Israel % n=539 Switzerland % n=166 Spain % n=493 Croatia, %, n=1270 Switzerland % n=129 USA % n=177 Italy % n=105 France % n=281 Turkey % n=938 Netherlands % n=189 Spain % n=378 Turkey % n=223 Turkey % n=173 Switzerland % n=156 Turkey % n=438 Croatia % n=122 France 2007

16 assumptions prescribing is (often) suboptimal (and often too excessive) and induces resistance

17 60 50 Taiwan Spain % Penicillin-nichtempfindliche Pneumokokken This is where a large graphic or chart can go. 10 Greece 20 USA Portugal Ireland Canada Luxemburg Iceland Austria Italy UK Belgium Australia Germany Sweden Finland Denmark Netherlands Norway 30 France 40 Antibiotikaverbrauch (definierte Tagesdosen [DDD]/1000 Tage) Albrich et al. Emerg Infect Dis 2004

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19 Group-level data Group-level data Imipenem DDD per 1000 pt days % 95% 90% 85% 80% 75% 70% Clin Infect Dis 2001; 33: Gram-negative bacilli Percent imipenem-susceptible

20 Individual-level data Probability of resistance Adjusted hazard ratio: 5.7 (95% CI, ) No imipenem Days in hospital Imipenem Clin Infect Dis 2001; 33:

21 Limitations to consider the limited evidence provided by purely observational (vs interventional studies) individual-level or group-level analysis (ecological bias)

22 7 FQR-EC and FQ Use E. coli (r = 0.79; p = 0.002) % FQ Resistance DDD/1000 patient-days Lautenbach, SHEA, 2002

23 FQR-EC and the Dow Jones Index E. coli (r=.96; p<.001) % FQ Resistance DJIA Courtesy: Y. Carmeli

24 assumptions prescribing is (often) suboptimal (and often too excessive) and reduces resistance optimized (and/or reduced) prescribing improves outcomes and can minimize or even reverse antimicrobial resistance

25 Interventions Endpoint: prescribing quality local guidelines, audit/education with feedback improvement in antimicrobial prescription included among the annual objectives linked to economic incentives in every department CMI 2013

26 Cisneros et al CMI 2013

27 Cisneros et al CMI 2013

28 Cisneros et al CMI 2013

29 Cisneros et al CMI 2013

30 Limitations consider endpoints prescribing density prescribing quality cost (from which perspective) patient outcomes vs microbial endpoints)

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36 Drug resistance in E. coli without apparent selection pressure Bean et al. JAC 2005

37 Limitations to consider design of interventional studies experimental (e.g. cluster-randomized) vs quasiexperimental (e.g. controlled before/after) analysis (e.g. time-series analysis, adverse events)

38 10 Intervention to Reduce Use of Alert Antibiotics 8 DDD/100 bed-days Months Change: DDD/100 P t test Slope <0.001 Ansari et al JAC 2003 Courtesy: Peter Davey, Dundee (UK)

39 Baseline Intervention Postintervention Kim et al JAC 2008

40 Limitations sustainability often not described which component is the most critical? (and needs most investment)

41 Limitations background epidemiology may be different confounding: cultural environment & prevalent prescribing etiquette risk for limited transferability/generalizability?? be aware of potentially adverse effects!!

42 assumptions & strategies what is optimized and/or reduced? no use by indication shorter treatment PK/PD-optimized treatment (dosing) use (or switch to) the ecologically ( collateral damage ) best-performing drugs

43 e.g. Bronchitis

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46 e.g. Uncomplicated UTI

47 double-blind trial n=253 women (18-70 years old) diclofenac vs norfloxacin for 3 days (with fosfomycin 3 g as rescue treatment) resolution of symptoms (day 3): 50% vs 77% (risk difference 27%, 95%CI 15-38%) 61% of patients in the diclofenac group ever consumed antibiotics

48 double-blind trial n=253 women (18-70 years old) diclofenac vs norfloxacin for 3 days (with fosfomycin 3 g as rescue treatment) resolution of symptoms (day 3): 50% vs 77% (risk difference 27%, 95%CI 15-38%) 61% of patients in the diclofenac group ever consumed antibiotics

49 assumptions & strategies what is optimized and/or reduced? no use by indication shorter treatment PK/PD-optimized treatment (dosing) use (or switch to) the ecologically ( collateral damage ) best-performing drugs

50 assumptions & strategies what is optimized and/or reduced? no use by indication shorter treatment PK/PD-optimized treatment (dosing) use (or switch to) the ecologically ( collateral damage ) best-performing drugs

51 Macrolide resistance among oral streptococci Malhotra-Kumar et al. Lancet 2007; 369:

52 Makrolide verändern nachhaltig die Mundhöhlenflora Amoxicillin auch?? Plazebokontrollierte Studie mit Amoxicillin (3x1g, n=37) oder Plazebo (n=38) über 1 Woche Rachenspülungen untersucht bis Tag 28 auf Streptokokken mit verminderter Empfindlichkeit auf Penicillin und Amoxicillin Ergebnisse: Malhotra-Kumar et al; K-1579

53 assumptions & strategies what is optimized and/or reduced? no use by indication shorter treatment PK/PD-optimized treatment (dosing) use (or switch to) the ecologically ( collateral damage ) best-performing drugs

54 Fluoroquinolone studies Some milestone studies, e.g. the 3F (French Fluoroquinolone Free-Study): multicenter trial showing substantial MRSA reduction following a 90% fluoroquinolone reduction (Charbonneau et al CID 2006) (!!)

55 Ceph + Fluorquinolone studies Recently many more 3C and 3C+ studies 3C: Ceph + Cipro/other FQs = C. difficile 3C+: Ceph + Cipro/other FQs = C. difficile ± ESBL ± MRSA

56 Talpaert et al JAC 2011

57 Talpaert et al JAC 2011

58 Talpaert et al JAC 2011

59 [109] Dancer et al IJAA 2013

60 Summary Stewardship is important but complex Best evidence so far regarding impact on C.difficile infection Very limited evidence for impact on MDR gram-negatives Many more interventional studies (hospital and outpatient setting) are needed

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