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Antimicrobial Stewardship: efective implementation for
improved clinical outcomes
José Miguel Cisneros Herreros
Infectious Diseases Department
University Hospital Virgen del Rocío, Sevilla, Spain
The Challenge of MDR and XDR infections; Barcelona September 2018
Competing interests
• Andalusian Health Service
• Ministry of Health (ISCIII), European Commission
• Novartis, Astellas, Pfizer, MSD, Janssen y Astra-Zeneca
2
Laxaminarayan R et al. Science 2016
Antimicrobial use
1
3
4
2015
https://ecdc.europa.eu/en/antimicrobial-resistance (access 2 July 2017)
SAMR P. aeruginosa CeftaR
E. coli QR Acinetobacter sp CR
2
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
2014
Spain: National plan to fight antimicrobial resistance 3
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
9
Evolution of E. coli and K. pneumoniae Cefalosporins Resistant
Informe JIACRA España; 5 de junio de 2018
Read RC et al. Lancet Infect Dis 2011
Spain, Belgium, Luxembourg and Cyprus are the only countries without EEII
The Specialty of Infectious Diseases in the EU
2016
4
10
The PIRASOA programme
11
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
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
14
Andalusian Public Healthcare Service
>90% population
34 Hospitals
• 8 University
27 primary care areas
17182 physicians
€ 8683 million
Definition
1. Quality programme
2. Integral • Healthcare Acquired Infections
• Antimicrobial Stewardship Programs
3. Professional lidership
4. Institutional support
15
The PIRASOA programme
PIRASOA
Hospitals
Infection control
ASP
Primary Care
ASP
Nursing home
ASP (2019)
16
Digital platform
Hospitals - Local team
Primary Care Area
- Local team
Scientific committee
Structure and organization
Reference laboratory
Clinical Management Units (UGCs) - Counselors
Clinical Management Units (UGCs) - Counselors
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
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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
Antibiotic use in hospitals D
DD
/10
00
OB
D
- 12%
26
923
835
849
835
876
803 794
822 818
770 770 778
815
780
757
778
813
1T2014 2T2014 3T2014 4T2014 1T2015 2T2015 3T2015 4T2015 1T2016 2T2016 3T2016 4T2016 1T2017 2T2017 3T2017 4T2017 1T2018
Carbapenem use D
DD
/10
00
OB
D
27
- 29%
59
48
55 55
53
52
56
51
48 47
50
46 46
49
50
44
42
1T2014 2T2014 3T2014 4T2014 1T2015 2T2015 3T2015 4T2015 1T2016 2T2016 3T2016 4T2016 1T2017 2T2017 3T2017 4T2017 1T2018
8406752
6215182
1T2014 2T2014 3T2014 4T2014 1T2015 2T2015 3T2015 4T2015 1T2016 2T2016 3T2016 4T2016 1T2017 2T2017 3T2017 4T2017 1T2018
Antimicrobial expenditure in hospitals
€
- 2.191.570 €
28
52 %
58 %
55 %
60 %
56 % 57 %
55 %
58 %
52 %
50 %
57 %
62 %
65 %
62 % 63 % 63 %
64 %
1T2014 2T2014 3T2014 4T2014 1T2015 2T2015 3T2015 4T2015 1T2016 2T2016 3T2016 4T2016 1T2017 2T2017 3T2017 4T2017 1T2018
Hand hygiene
%
+23%
29
0,000
0,050
0,100
0,150
0,200
0,250
0,300
0,350
0,400
0,450
1T2014 2T2014 3T2014 4T2014 1T2015 2T2015 3T2015 4T2015 1T2016 2T2016 3T2016 4T2016 1T2017 2T2017 3T2017 4T2017 1T2018
Evolution of MDR bacteria
E. coli BLEE KP BLEE EPCarbepemasas PAMR ABMR SAMR C. difficile
Nº
iso
late
s/1
00
0 O
BD
30
31
Nº
iso
late
s /
10
00
OB
D
Evolution of enterobacterial CR infections/colonizations
0,12 0,12
0,09
0,1
0,08
0,09
0,08 0,08
0,09
0,08 0,08
0,07
0,08
0,09
0,08
0
0,02
0,04
0,06
0,08
0,1
0,12
0,14
1T2014 2T 3T 4T 1T2015 2T 3T 4T 1T2016 2T 3T 4T 1T2017 2T 3T
Clinical outcomes in hospitals
32
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.
33
Antibiotic use in primary care
25
19,8
16,6
21,1
27,3
18,7
15,6
19,5
22,6
18,4
14,4
18,5
21,6
16,5
13,9
18,3
0
5
10
15
20
25
30D
DD
/10
00
hab
. día
- 26,8% P <0,05
Annual antibiotics consumption in Primary Care
– 2.8 millon DDD
34
20,6 20,3
18,7
17,5
15,5
16
16,5
17
17,5
18
18,5
19
19,5
20
20,5
21
2014 2015 2016 2017
– 4.8 millon DDD
DD
D/1
00
0 h
ab. d
ía
21,5
18,5
17,5
19,4
24,0
14,6 14,1
10,0
12,0
14,0
16,0
18,0
20,0
22,0
24,0
26,0
2008 2009 2010 2011 2012 2013 2014 2015 2016 2017
Andalucía España (excl. AND) Alemania
PIRASOA
Antibiotic use in primary care: Andalucia, Spain and Germany
+ 23% +2,6 p<0,01
- 19% - 1,7 p<0,01
P =0,7
35
DD
D/1
00
0 h
ab. d
ía
10,0
11,5
13,0
14,5
16,0
17,5
19,0
20,5
22,0
23,5
2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020
DD
D J
01
po
r 1
00
0 p
eo
ple
PIRASOA
Antibiotic use in primare care, Andalucia: Estimated prediction
36
37
11
8,7
7,9
9,1
10,5
7,4 6,7
7,5 8,2
6,4
5,6 6,3
7
5,5 5
5,6
0
2
4
6
8
10
12
DD
D/1
00
0 h
ab. d
ía
Amoxicillin/clavulanic use in primary care
- 49% P <0,05
+2,9% (p<0,01
- 10,5% p<0,05)
Ecological impact in primary care: E. coli BLEE
38 Peñalva G et al. ECCMID 2017
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;65:1992–9
41
Antimicrobial use
- 217 DDD/1000 OBDs
-19,9%
Clinical Infectious Diseases® 2017;65:1992–9
42
Incidence of nosocomial bloodstream infections by MDR bacteria and candidemia
Clinical Infectious Diseases® 2017;65:1992–9
43
Incidence of nosocomial bloodstream infections by no-MDR bacteria and candidemia
Clinical Infectious Diseases® 2017;65:1992–9
44
Mortality of nosocomial bloodstream infections by MDR bacteria and candidemia
Clinical Infectious Diseases® 2017;65:1992–9
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
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
Local teams:
• 638 professionals
Thousands of professionals of the Andalusian Public Healthcare System who have participated
Reference Laboratory
Scientific Committee (18)
Scientific societies (10)
46
Acknowledgments
@guiaprioam http://guiaprioam.com/
http://pirasoa.iavante.es/
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