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
Competing interests Andalusian Health Service Ministry of Health (ISCIII), European Commission Novartis, Astellas, Pfizer, MSD, Janssen y Astra-Zeneca 2
Antimicrobial use 1 Laxaminarayan R et al. Science 2016 3
SAMR P. aeruginosa CeftaR 2 2015 E. coli QR Acinetobacter sp CR https://ecdc.europa.eu/en/antimicrobial-resistance (access 2 July 2017) 4 4
Clinical impact MDR infections Design: - 82 hospitals (26% Spain) - March 12 to 18 - Follow-up 30 days after diagnosis Results: - 903 pacients with MDR infections - 177 deaths (19,6%) Estimates for Spain in 2018: - 180.600 pacients with MDR infections - 35.400 deaths
3 Spain: National plan to fight antimicrobial resistance 2014 6
Antimicrobials consumption in hospitals http://www.resistenciaantibioticos.es/es/profesionales/vigilancia/mapas-de-consumo
Profile of prescriptions Colistina +58% Carbapenem + 42% Informe JIACRA España; 5 de junio de 2018
Evolution of E. coli and K. pneumoniae Cefalosporins Resistant Informe JIACRA España; 5 de junio de 2018 9
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 2011 10
The PIRASOA programme Institutional Programme for the Prevention and Control of Healthcare Associated Infections and Appropriate Use of Antimicrobials http://pirasoa.iavante.es/ https://www.protocols.io/view/the-pirasoa-programme-design-structure-organisatio-r3bd8in 11
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
The setting: Andalucía 8.4 M habitants 13
Andalusian Public Healthcare Service >90% population 34 Hospitals 8 University 27 primary care areas 17182 physicians 8683 million 14
Definition 1. Quality programme 2. Integral Healthcare Acquired Infections Antimicrobial Stewardship Programs 3. Professional lidership 4. Institutional support 15
The PIRASOA programme PIRASOA Hospitals Primary Care Nursing home Infection control ASP ASP ASP (2019) 16
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
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
Indicators n = 171 - Antimicrobials: use, quality use, cost - Resistance: density in clinical samples - Nosocomial infections: prevalence and incidence - Clínical: mortality of patients with bacteremia 19
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 = 17 5. Educational interviews n = 79841 20
2. Massive Online Open Course (MOOC) n = 6979 participants 21
Educational interviews: methodology Cisneros JM et al. Clin Microbiol Infect 2014;20:82-8 Molina J et al. Clin Infect Dis 2017;65:1992 9 22
Educational interview form
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
PIRASOA s RESULTS January 2014 to Marz 2018 25
DDD/1000 OBD Antibiotic use in hospitals 923 876 835 849 835-12% 803 794 822 818 815 813 770 770 778 780 778 757 1T2014 2T2014 3T2014 4T2014 1T2015 2T2015 3T2015 4T2015 1T2016 2T2016 3T2016 4T2016 1T2017 2T2017 3T2017 4T2017 1T2018 26
DDD/1000 OBD Carbapenem use 59 56 48 55 55 53 52 51 48 47 50 46 46 49 50-29% 44 42 1T2014 2T2014 3T2014 4T2014 1T2015 2T2015 3T2015 4T2015 1T2016 2T2016 3T2016 4T2016 1T2017 2T2017 3T2017 4T2017 1T2018 27
Antimicrobial expenditure in hospitals 8406752-2.191.570 6215182 1T2014 2T2014 3T2014 4T2014 1T2015 2T2015 3T2015 4T2015 1T2016 2T2016 3T2016 4T2016 1T2017 2T2017 3T2017 4T2017 1T2018 28
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 1T2018 29
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
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
Clinical outcomes in hospitals Variation Q1- Q14 Trend QPC CI95% p value Overall inappropriate treatment rate (%) 50.6-29.4-4.1% (-4.7%,-3.5%) <0.001 Total DDDs/1000 OBD 923-780 -0.9% (-1.3%,-0.5%) <0.001 DDDs/1000 OBD carbapenems 64.9-55.3-1.2% (-1.8%,-0.5%) 0.002 DDDs/1000 OBD amoxycillin/clavulanic 183.1-153.9-1.5% (-1.8%,-1.3%) <0.001 DDDs/1000 OBD piperacillin/tazobactam 50.0-45.9 0.4% (0%,0.7%) 0.038 DDDs/1000 OBD quinolones 194.4-116.3-1.6% (-1.9%,-1.2%) <0.001 DDDs/1000 OBD antifungal agents 42.7-36.4-1.5% (-2.1%,-0.8%) <0.001 ID multidrug-resistant pathogens/1000 OBD (1) 1.30-0.98-2.3% (-3.3%,-1.3%) <0.001 Overall crude mortality rate associated with bacteraemias (%) (2) 16.4-15.3 0.1% (-0.8%,1.1%) 0.748 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
DDD/1000 hab. día Antibiotic use in primary care 30 25 25 27,3 20 15 19,8 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 <0,05 10 5 0 33
DDD/1000 hab. día Annual antibiotics consumption in Primary Care 21 20,5 20,6 20,3 20 19,5 4.8 millon DDD 19 18,7 18,5 18 17,5 17,5 2.8 millon DDD 17 16,5 16 15,5 2014 2015 2016 2017 34
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 10,0 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 PIRASOA 35
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 10,0 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 PIRASOA 36
DDD/1000 hab. día Amoxicillin/clavulanic use in primary care 12 10 11 10,5 8 6 4 8,7 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 <0,05 2 0 37
Ecological impact in primary care: E. coli BLEE +2,9% (p<0,01-10,5% p<0,05) Peñalva G et al. ECCMID 2017 38
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
Clinical Infectious Diseases 2017;65:1992 9 40
Antimicrobial use - 217 DDD/1000 OBDs -19,9% Clinical Infectious Diseases 2017;65:1992 9 41
Incidence of nosocomial bloodstream infections by MDR bacteria and candidemia Clinical Infectious Diseases 2017;65:1992 9 42
Incidence of nosocomial bloodstream infections by no-mdr bacteria and candidemia Clinical Infectious Diseases 2017;65:1992 9 43
Mortality of nosocomial bloodstream infections by MDR bacteria and candidemia Clinical Infectious Diseases 2017;65:1992 9 44
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
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
Acknowledgments @guiaprioam http://guiaprioam.com/ http://pirasoa.iavante.es/ 47