Antibiotic stewardship

Herlev og Gentofte Hospital Antibiotic stewardship Erfarenheter från Köpenhamn Magnus Arpi Klinisk Mikrobiologisk afdeling Herlev og Gentofte Hospital 22. november 2016

Hvordan skal man måle effekten af et antibiotic stewardship program? Strategiske mål? Procesmål? Resultatmål?

Strong recommendations Enough data points before and after the intervention Adequate evaluation of seasonal variation requires a minimim of 24 monthly measures. Optimally 24 data points before and after the intervention A minimum of 100 observations at each time point to achieve an accetable level of variability of the estimate at each time point Ramsay et al. J Antimicrob Chemother 2003; 52: 764-771

Strong recommendations Interrupted times series analysis with segmented regression analysis * Estimates how much an intervention changed an outcome, immediately and over time * Comparison of the means of data before and after the intervention can either overestimate or underestimate the effect size Include a control group * Without a control group, it is impossible to say whether or not any observed differences before and after the intervention would have happened anyway Ramsay et al. J Antimicrob Chemother 2003; 52: 764-771

Figure 1. Graphic illustration of segmented regression analysis of interrupted time series data Craig Ramsay et al. J. Antimicrob. Chemother. 2003;52:764-771

Antibiotic stewardship at Herlev Hospital

Consumption of cephalosporins and fluoroquinolones at Herlev Hospital DDD/1000 ocupied bed days 200 180 160 140 120 100 80 Cephalosporins Fluoroquinolones 60 40 20 0 2002 2003 2004 2005 2006 2007 2008 2009 2010

Correlation between antibiotic consumtion and og resistance 18 E. coli Cefuroxim 16 14 12 10 8 6 % resistance DDD/100 occupied bed days Ciprofloxacin 4 2 0 20 18 16 14 12 10 8 6 4 2 0 2002 2003 2004 2005 2006 2007 2008 2009 2010 2002 2003 2004 2005 2006 2007 2008 2009 2010 % resistance DDD/100 occupied bed days

Stevens et al. CID 2011; 53: 42-48

Medicinsk afdeling - Cefalosporiner 450 400 1. 2. 3. DDD/1000 sengedage 350 300 250 200 150 100 50 Cefalosporiner Mean 3SD 3SD Mål - 11 12 1-2010 2 3 4 5 6 7 8 9 10 11 12 1-2011 2 3 4 5 6 7 8 9 10 11 12 1-2012 2 3 4 Mean = gennemsnitligt forbrug de seneste 30 måneder 3 SD = 3 standarddeviationer Mål = afdelingsspecifikt mål for antibiotikaindsatsen DDD = Daglige Definerede Døgndoser. Antibiotikaforbruget angives som DDD/1000 sengedage, som er et godt mål på antibiotikatrykket og som tillader sammenligninger mellem forskellige afdelinger og forskellige hospitaler 1. Antibiotika Audit - skriftlig rapport 2. Feed-back på audit til alle læger 3. Ændring af antibiotikavejledning

Antibiotic stewardship - Strategier Information alene Antibiotika audit med intervention og feedback Autorisation/klausulering

Monitoring antibiotic consumption in the Capital Region of Denmark

Cefuroxim

Ciprofloxacin

Antibiotic Coverage Bacteremia, Herlev Hospital Before 2011 After 2011 P-value Ampicillin + Gentamicin 90,7 % 92,1 % 0,13 Cefuroxime + Gentamicin 85,6 % 89,6 % <0,01 Cefuroxime + Ciprofloxacin 83,8 % 88,0 % <0,01 Cefuroxime 69,9 % 78,6 % <0,01 Ciprofloxacin 47,8 % 51,0 % 0,04 Ampicillin 41,6 % 45,1 % 0,03 Gentamicin 66,6 % 70,9 % 0,04 Piperacillin/tazobactam 96,6 % 97,1 % 0,40

Antibiotic coverage of empiric treatment of bacteremia at Herlev Hospital

Clostridium difficile

Anæstesiologisk afd. I Brystkirurgisk afd. F og Plastikkirurgisk afd. V Børneafdeling E Gastroenheden, afd. D Gynækologisk afd. G Obstetrisk afd. G Hjertemedicinsk afd. S Hud- og allergiafd. U, GE Lungemedicinsk afd. Y, GE Medicinsk hæmatologisk afd. L Medicinsk afd. C, GE Medicinsk. afd. O Nefrologisk afd. B Neurologisk afd. N Onkologisk afd. R Ortopædkirurgisk afd. T Urologisk afd. H inkl. palliation Herlev og Gentofte Hospital DDD/1000 sengedage Consumption of fluoroquinolones at Herlev and Gentofte Hospital 2015 450 400 350 300 250 200 150 100 50 Forbrug pr. 1000 sengedage Mål 0

Boel et al. Eur J Clin Microbiol Infect Dis 2015; 34: 1475-1484

Appropriateness of empiric treatment Bacteremia, Herlev Hospital 2010 (n=699) 2011 (n=820) 2012 (n=843) Appropriate treatment 78.8% (551) 84.9% (696) 85.7% (722)

Mortality in bacteremia at Herlev Hospital 2010 (n=692) 2011 (n=792) 2012 (n=773) 30-day s mortality 21.5% (149) 20.7% (164) 17.9% (138)

Charlson Comorbidity Index Bacteremia, Herlev Hospital 2010 (n=692) 2011 (n=792) 2012 (n=773) Low (0) 23.0% (159) 24.9% (197) 20.0% (154) Medium (1-2) 41.9% (290) 39.4% (312) 42.8% (331) High (>2) 35.1% (243) 35.7% (283) 37.3% (288)

Effect on readmission All first episodes of bacteraemia (n=2008) Crude 30-day readmission HR (CI 95%) P-value Adjusted* 30-day readmission HR (CI 95%) Treatment regimen (ref. old regime) All-cause readmission 1.01 (0.87, 1.19) 0.87 1.05 (0.87, 1.25) 0.24 Acute readmission 1.04 (0.87, 1.23) 0.68 1.09 (0.90, 1.33) 0.38 Infection-related readmission 0.97 (0.65, 1.46) 0.90 1.06 (0.67, 1.67) 0.82 Appropriate empirical treatment (ref. inappropriate treatment) All-cause readmission 0.82 (0.66, 1.01) 0.07 0.91 (0.73, 1.13) 0.38 Acute readmission 0.72 (0.57, 0.91) <0.01 0.81 (0.64, 1.01) 0.06 Infection-related readmission 0.67 (0.40, 1.14) 0.14 0.74 (0.44, 1.26) 0.27 P-value *Adjusted for age, sex, Charlson Comorbidity Index score, origin of infection, study year and admission to ICU by using Cox proportional hazard regression.

Thønnings et al. Clinical Microbiology and Infection 2016, http://dx.doi.org/10.1016/cmi.2016.06.006

New guidelines in the Capital Region of Denmark

Reducere hospitalserhvervet antibiotikaresistens i Region Hovedstaden Beslutningsstøtte Indikation for behandling Standardpakker -profylakse/kirurgi -empirisk -målrettet Forbrug/indkøb (DDD) Mål: Reduktion = 10 % Dosis Behandlingsvarighed Relevant indikation før start af behandling Relevante diagnostiske prøver før behandlingsstart Administrationsform Stopdato Case-mix Feedback på adfærd Forbrugsmønster Mål: Andel penicillin = 70 % Præparatvalg/ Optimalt førstevalg Opfølgning på prøvesvar mhp skift fra empirisk til målrettet behandling Skift fra IV til PO-behandling Restriktion af udvalgte antibiotika

5 quality metrics for antimicrobial stewardship programmes 1. Days of therapy per 1000 patient-days 2. Number of patients with specific organisms that are drug resistant 3. Mortality related to antimicrobial-resistant organisms 4. Conservable days of therapy among patients with CAP, SSTI or BSI 5. Unplanned hospital readmission within 30 days after discharge from the hospital with the diagnosis CAP, SSTI or BSI CAP = community-acquired pneumonia SSTI = skin and soft-tissue infections BSI = bloodstream infection Morris et al. Infect Control Hosp Epidemiol 2012; 33(5): 500-506

Problem areas * Fear of aminoglycosides * Self-reported penicillin allergy * High consumption of penicillins with β-lactamase inhibitors

Paterson et al. J Gen Intern Med 1998; 13: 735-739

Aminoglykosider Cochraneanalyse 2014 Doseringinterval 58 studier

Aminoglykosider Cochraneanalyse 2014 Behandlingslængde 41 studier

Penicillin allergy DANGEROUS DIAGNOSIS!! Confirmation is mandatory

Penicillin allergy Borch et al. Ugeskr Læger 2003; 165/33: 3157-3161 109 patients with self-reported penicillin allergy -15 patients were tested positive (13,7%) -3 patients showed systemic reactions (2,8%) ---------------------------------------------------------------------- Kerr JR. Br J Clin Pract 1994; 48(1): 5-7 270 patients with self-reported penicillin allergy - 14,3% were tested positive - 1,1% (3 patients) showed type-1 allergy

Undersøgelse af penicillinallergi i Californien 2010-2012 Macy et al. J Allergy Clin Immunol 2014; 133: 790-796 * 51.582 indlagte patienter med Cave penicillin (11,9 % af alle indlagte patienter) * Sammenlignes med dobbelt så stor kohorte uden Cave penicillin matchet på køn, alder, indlæggelsesdato og ICD-9 diagnoser

Patienter med Cave penicillin * behandles oftere med fluoroquinoloner, clindamycin og vancomycin (p<0.001) * har 23,4% flere Clostridium difficilie infektioner * har 14,1% flere MRSA påvist * har 30,1% flere VRE påvist * er indlagt 0,6 dage længere Macy et al. J Allergy Clin Immunol 2014; 133: 790-796

Patienter med Cave penicillin * har højere hospitalsmortalitet (OR 1,56) * ligger oftere på intensiv (OR 1,42) * får oftere kombinationsbehandling med antibiotika (OR 1,61) Charneski et al. Pharmacotherapy 2011; 31(8): 742-747

1-2007 4 7 10 1-2008 4 7 10 1-2009 4 7 10 1-2010 4 7 10 1-2011 4 7 10 1-2012 4 7 10 1-2013 4 7 10 1-2014 4 7 10 1-2015 4 7 DDD/1000 sengedage Consumption of β-lactamase inhibitors at Herlev and Gentofte Hospital 350 300 250 200 150 Gentofte matriklen Betalactamasehæmmere Herlev matriklen Betalactamasehæmmere 100 50 0

Saust et al. Scand J Prim Health Care 2016, http://dx.doi.org/10.1080/02813432.2016.1207143

Herlev Hospital 18. novemnber 2016