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

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

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/

47