Antimicrobial Stewardship: efective implementation for improved clinical outcomes

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1 The Challenge of MDR and XDR infections; Barcelona September 2018 Antimicrobial Stewardship: efective implementation for improved clinical outcomes José Miguel Cisneros Herreros Infectious Diseases Department University Hospital Virgen del Rocío, Sevilla, Spain

2 Competing interests Andalusian Health Service Ministry of Health (ISCIII), European Commission Novartis, Astellas, Pfizer, MSD, Janssen y Astra-Zeneca 2

3 Antimicrobial use 1 Laxaminarayan R et al. Science

4 SAMR P. aeruginosa CeftaR E. coli QR Acinetobacter sp CR (access 2 July 2017) 4 4

5 Clinical impact MDR infections Design: - 82 hospitals (26% Spain) - March 12 to 18 - Follow-up 30 days after diagnosis Results: pacients with MDR infections deaths (19,6%) Estimates for Spain in 2018: pacients with MDR infections deaths

6 3 Spain: National plan to fight antimicrobial resistance

7 Antimicrobials consumption in hospitals

8 Profile of prescriptions Colistina +58% Carbapenem + 42% Informe JIACRA España; 5 de junio de 2018

9 Evolution of E. coli and K. pneumoniae Cefalosporins Resistant Informe JIACRA España; 5 de junio de

10 4 The Specialty of Infectious Diseases in the EU Spain, Belgium, Luxembourg and Cyprus are the only countries without EEII 2016 Read RC et al. Lancet Infect Dis

11 The PIRASOA programme Institutional Programme for the Prevention and Control of Healthcare Associated Infections and Appropriate Use of Antimicrobials

12 General objectives 1. To reduce the incidence of HAIs until reaching the level of the European countries with the best outcomes. 2. To optimize the use of antibiotics until reaching the level of the European countries with the best outcomes. 12

13 The setting: Andalucía 8.4 M habitants 13

14 Andalusian Public Healthcare Service >90% population 34 Hospitals 8 University 27 primary care areas physicians 8683 million 14

15 Definition 1. Quality programme 2. Integral Healthcare Acquired Infections Antimicrobial Stewardship Programs 3. Professional lidership 4. Institutional support 15

16 The PIRASOA programme PIRASOA Hospitals Primary Care Nursing home Infection control ASP ASP ASP (2019) 16

17 Structure and organization Scientific committee Hospitals - Local team Primary Care Area - Local team Clinical Management Units (UGCs) - Counselors Clinical Management Units (UGCs) - Counselors Digital platform Reference laboratory 17

18 PIRASOA teams Profesionals n = 638 Local teams in hospitals (HAIs and ASP) n = 34 - Infectious diseases - Pharmaceuticals - Microbiologists - Preventivits - Nurses Local teams in primary care areas (ASP) n = 27 - Primary care doctor - Pediatrician - Pharmaceuticals 18

19 Indicators n = Antimicrobials: use, quality use, cost - Resistance: density in clinical samples - Nosocomial infections: prevalence and incidence - Clínical: mortality of patients with bacteremia 19

20 Interventions: training 1. Symposium (18th november) n = 4 2. Massive Online Open Course (MOOC) n = 6979 participants Basic ASP ASP for severe infections Infection Control Infection Control and ASP (forthcoming) 3. Local guides for antimicrobial therapy 4. Quarterly reports n = Educational interviews n =

21 2. Massive Online Open Course (MOOC) n = 6979 participants 21

22 Educational interviews: methodology Cisneros JM et al. Clin Microbiol Infect 2014;20:82-8 Molina J et al. Clin Infect Dis 2017;65:

23 Educational interview form

24 Institucional support Official program Andalusian Health Service Presentation in the Andalusian Parliament Official councils of Medicine, Pharmacists and Dentists The management agreements Specific budget for reference Laboratory 24

25 PIRASOA s RESULTS January 2014 to Marz

26 DDD/1000 OBD Antibiotic use in hospitals % T2014 2T2014 3T2014 4T2014 1T2015 2T2015 3T2015 4T2015 1T2016 2T2016 3T2016 4T2016 1T2017 2T2017 3T2017 4T2017 1T

27 DDD/1000 OBD Carbapenem use % T2014 2T2014 3T2014 4T2014 1T2015 2T2015 3T2015 4T2015 1T2016 2T2016 3T2016 4T2016 1T2017 2T2017 3T2017 4T2017 1T

28 Antimicrobial expenditure in hospitals T2014 2T2014 3T2014 4T2014 1T2015 2T2015 3T2015 4T2015 1T2016 2T2016 3T2016 4T2016 1T2017 2T2017 3T2017 4T2017 1T

29 Hand hygiene 60 % 62 % 65 % 62 % 63 % 63 % 64 % % 52 % 58 % 55 % 56 % 57 % 55 % 58 % 52 % 50 % 57 % +23% 1T2014 2T2014 3T2014 4T2014 1T2015 2T2015 3T2015 4T2015 1T2016 2T2016 3T2016 4T2016 1T2017 2T2017 3T2017 4T2017 1T

30 Nº isolates/1000 OBD 0,450 Evolution of MDR bacteria 0,400 0,350 0,300 0,250 0,200 0,150 0,100 0,050 0,000 1T2014 2T2014 3T2014 4T2014 1T2015 2T2015 3T2015 4T2015 1T2016 2T2016 3T2016 4T2016 1T2017 2T2017 3T2017 4T2017 1T2018 E. coli BLEE KP BLEE EPCarbepemasas PAMR ABMR SAMR C. difficile 30

31 Nº isolates / 1000 OBD Evolution of enterobacterial CR infections/colonizations 0,14 0,12 0,12 0,12 0,1 0,1 0,08 0,09 0,08 0,09 0,08 0,08 0,09 0,08 0,08 0,08 0,09 0,08 0,06 0,07 0,04 0,02 0 1T2014 2T 3T 4T 1T2015 2T 3T 4T 1T2016 2T 3T 4T 1T2017 2T 3T 31

32 Clinical outcomes in hospitals Variation Q1- Q14 Trend QPC CI95% p value Overall inappropriate treatment rate (%) % (-4.7%,-3.5%) <0.001 Total DDDs/1000 OBD % (-1.3%,-0.5%) <0.001 DDDs/1000 OBD carbapenems % (-1.8%,-0.5%) DDDs/1000 OBD amoxycillin/clavulanic % (-1.8%,-1.3%) <0.001 DDDs/1000 OBD piperacillin/tazobactam % (0%,0.7%) DDDs/1000 OBD quinolones % (-1.9%,-1.2%) <0.001 DDDs/1000 OBD antifungal agents % (-2.1%,-0.8%) <0.001 ID multidrug-resistant pathogens/1000 OBD (1) % (-3.3%,-1.3%) <0.001 Overall crude mortality rate associated with bacteraemias (%) (2) % (-0.8%,1.1%) : Multiresistant both Pseudomonas aeruginosa and Acinetobacter baumanii, methicillin-resistant Staphylococcus aureus, vancomicin-resistant Enterococcus sp, Extended-Spectrum β-lactamase-producing both Escherichia coli and Klebsiella Pneumoniae and carbapenemase-producing Enterobacteriaceae. 2: Bacteraemias caused by Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumanii, Staphylococcus aureus and Candida sp. 32

33 DDD/1000 hab. día Antibiotic use in primary care , ,8 16,6 21,1 18,7 15,6 19,5 22,6 18,4 14,4 18,5 21,6 16,5 13,9 18,3-26,8% P <0,

34 DDD/1000 hab. día Annual antibiotics consumption in Primary Care 21 20,5 20,6 20, ,5 4.8 millon DDD 19 18,7 18, ,5 17,5 2.8 millon DDD 17 16, ,

35 DDD/1000 hab. día Antibiotic use in primary care: Andalucia, Spain and Germany 26,0 Andalucía España (excl. AND) Alemania 24,0 24,0 + 23% +2,6 p<0,01 22,0 20,0 21,5 18,0 16,0 19,4 18,5 17,5-19% - 1,7 p<0,01 14,0 14,6 14,1 P =0,7 12,0 10, PIRASOA 35

36 DDD J01 por 1000 people Antibiotic use in primare care, Andalucia: Estimated prediction 23,5 22,0 20,5 19,0 17,5 16,0 14,5 13,0 11,5 10, PIRASOA 36

37 DDD/1000 hab. día Amoxicillin/clavulanic use in primary care , ,7 7,9 9,1 7,4 6,7 7,5 8,2 6,4 5,6 6,3 7 5,5 5 5,6-49% P <0,

38 Ecological impact in primary care: E. coli BLEE +2,9% (p<0,01-10,5% p<0,05) Peñalva G et al. ECCMID

39 Conclusions: 1. It is possible to implement and maintain an ASP in an entire health system. 2. This program is able to optimize the use of antimicrobials agents, reducing total consumption and improving the prescription profile, and probably contributing to reduce the incidence of MDR pathogens, without increasing the crude death rate associated with bloodstream infections. 39

40 Clinical Infectious Diseases 2017;65:

41 Antimicrobial use DDD/1000 OBDs -19,9% Clinical Infectious Diseases 2017;65:

42 Incidence of nosocomial bloodstream infections by MDR bacteria and candidemia Clinical Infectious Diseases 2017;65:

43 Incidence of nosocomial bloodstream infections by no-mdr bacteria and candidemia Clinical Infectious Diseases 2017;65:

44 Mortality of nosocomial bloodstream infections by MDR bacteria and candidemia Clinical Infectious Diseases 2017;65:

45 Conclusions: The results of this study show that the decrease and better use of antibiotics achieved by our ASP had a sustained ecological and clinical impact, reducing the incidence and mortality rate of hospital-acquired candidemia and MDR BSIs 45

46 Acknowledgments Local teams: 638 professionals Thousands of professionals of the Andalusian Public Healthcare System who have participated Reference Laboratory Scientific Committee (18) Scientific societies (10) Andalusian Government Health Counselor Secretary of Public Health Managing Director of the Andalusian Health Service General Director of Health Care Support Services of the Andalusian Health Service Strategic Direction of IT IAVANTE Canal SUR television 46

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