3. COMMON CHALLENGES IN CONTAINING ANTIMICROBIAL RESISTANCE
COMMON CHALLENGES IN
CONTAINING
ANTIMICROBIAL RESISTANCE
Budiono Santoso
International Network for Rational Use of Drugs (INRUD) – Indonesia,
Gadjah Mada University MedicaL Alumni Association
Personal background & introduction
Professionals in
medicines area
- INRUD
- US Pharmacopeia
- IUPHAR Clinical
Pharmacology
- WHO Expert
Committee
Clinical
Pharmacologist
Academician &
researcher
Gadjah Mada
University
1977 - 1999
Former Team Leader
in Pharmaceuticals &
Health Technology
WHO Western Pacific
Regional Office
1999 - 2013
ANTIMICROBIAL RESISTANCE
What are the issues ?
´ Increasing incidence of resistance
´ Antibiotics
´ Anti parasitic
´ Antifungals
´ Anti HIV/AIDS
´ Well documented in different
settings, both developed and
developing countries.
´ Different levels of awareness and
commitment
SILENT EPIDEMICS
with
serious impact on
health
Leading infectious killers, global, millions of
deaths (WHO surveillance 1998)
´ Malaria - choroquine resistance in
81/92 countries
4
´ Tuberculosis : 0-22 % primary MDR
´ HIV/AIDS : 0-25 % primary
3.5
resistance to at least one antiretroviral
3
2.5
´ Pneumonia and bacterial
meningitis
2
1.5
´ 0-70 % penicillin resistance
S.pneumoniae
1
´ Diarrhoea: shigellosis
0.5
0
ARI
AIDS
Diarrhoeal
diseases
TB
Malaria
´ 10-90% ampicillin resistance
´ 5-95% cotrimoxazole resistance
´ Hospital infections : 0-70% S.
Aureus resistance to all penicillins &
cephalosporins
Global Surveillance report 2014
´
Jeopardizing the future treatment of
“ ….. The data reviewed for the
report reveals serious problems and
worsening trends in antimicrobial
resistance in some nations in the
Southeast Asian region”.
´ Pneumonia and meningitis
´ Shigellosis
´ Sepsis including neonatal sepsis
´ Hospital infections
´ Urinary tract infections
´ Post surgery infections
´ Gonorrhea
´ Malaria
´ TB
´ Cancer chemotherapy
´ Major surgery, etc
Antimicrobial Resistance WHO Global surveillance report 2014
E Coli
Resistance to 3rd generation
cephalosphorins
Klebsiella pneumoniae
Resistance to 3rd generation
cephalosporins
Staphylococcus aureus:
Resistance to methicilline
(MRSA)
Streptococcus pneumoniae:
Resistance, or nonsusceptibility, to penicillin
Shigella species:
Indonesia
(%)
10 (ctx)
13.8 (cro)
53.3 (ctx);
67.2 (cro)
-
Malaysia
(%)
Thailand (%)
Philippines
(%)
14.9 (caz);
18 (cro);
20 (ctx)
30.5 (caz);
41.4 (cro);
42.7 (ctx)
26.7
37.4 (caz);
40.3 (cro);
41.1 (ctx)
30
21.1 (cro);
20.8 (caz);
24 (ctx)
17.3
21.6 (cef);
24.2 (oxa)
54.9
-
17.5
47
43
-
2.9
76
44.4
Antimicrobial resistance in Indonesia
( AMRIN STUDY, 2000 – 2005)
Community infections
( n = 2494)
´ E Coli Resistance (43%)
´ E Coli Resistance ( 81 %)
´ Ampicillin
- 34 %
´ Ampicillin
- 73 %
´ Co-trimoxazole
- 29 %
´ Co-trimoxazole
- 56 %
´ Chloramphenicol - 25 %
MOH, 2015
Hospital infections
( n = 781 )
´ Chloramphenicol - 43 %
´ Cyprofloxazine
- 22 %
´ Gentamycin
- 18 %
Antimicrobial Resistance –
What could be the impacts ?
Prolonged
Treatment &
Treatment failure
increased
morbidity &
Mortality
Escalating
healthcare cost
& reduced
access and
coverage
Potential loss of
effective therapy in
the future
Cost ratio of alternative drugs to 1st line antimicrobials:
2nd, 3rd, and 4th line drugs may be 2 to 90 times costlier
Cost ratio to
1st line drug
80
70
60
50
Alternative
drugs
4th
40
30
20
3rd
10
2nd
0
Gonorrhoea
Malaria
Shigellosis
Pneumonia
Cost per
0.03 US$
0.05 US$
0.06 US$
0.14 US$
patient with 1st
line drug Source: WHO model formulary and relevant WHO clinical guidelines on the WHO website
2004, and Management Sciences for Health's 2004 International Drug Price Indicator
Guide
World Health Organization
Essential Medicines and Pharmaceutical Policy
Survival after pneumococcus pneumoniae with
sepsis before and after the discovery of penicillin
WHO, 2014
Antimicrobial Resistances
Possible risk factors
Overuse,
indiscriminate
use, underdosage by
providers and
consumers
Uncontrolled
distribution of
antimicrobials
The use of
antimicrobials for
human in
veterinary and
agricultures
Substandard
quality of
antimicrobials
products
60
Penicillin-resistant S. pneumoniae (%)
Taiwan
50
Spain
France
40
USA
Greece
30
Portugal
Ireland
20
Austria
Canada
Luxemburg
Iceland
Italy
Belgium
UK
Australia
Germany
Finland
Sweden
Albrich, Monnet and Harbarth,
Denmark
Emerg Infect Dis.; 2004; 10(3):514-7
Netherlands
Norway
10
0
0
10
20
30
40
Total antibiotic use (DDD/1000 population/day)
World Health Organization
Essential Medicines and Pharmaceutical Policy
Antimicrobial Resistance
What need to be done ?
´ Improve AMR monitoring and surveillance
´ Enforce regulation
´ Quality production of antimicrobial products
´ Quality surveillance
´ Controlled distribution
´ Quality use of antimicrobials
´ Antimicrobials usage surveillance
´ Antibiotic policy as part of national medicines policy
´ Advocacy and information for providers and consumers
´ One Health approach - Use of antimicrobials in veterinary and agriculture
Antimicrobial resistance
What have been done at global, regional and
national levels?
´ Global & regional levels
´ Intercountry consultation at regional and global level
´ Inter-partners consultation – donors, industries, non governmental institutions, academic institutions.
´ WHO Global Strategy for Containment of Antimicrobial Resistance, 2001
´ WHO Global Action on Antimicrobial Resistance 2015
´ National level
´ National training & workshop on AMR
´ National action plan for Containment of Antimicrobial Resistance.
´ Subnational/institutional/hospital levels
´ Implementing relevant actions : surveillance, RDU, hospital policy etc ?
´ Community levels
´ Public education and advocacy ?
WHO Global Strategy for Containment
of Antimicrobial Resistance 2001
National Task Force to coordinate 67 interventions in
six key areas
1. Strengthen surveillance capabilities
2. Improve use of antimicrobials
3. Improve access to appropriate antimicrobials
4. Reduce disease burden & spread of infection
5. Enforce regulations & legislation
6. Develop appropriate new drugs & vaccines
WHO Global Action Plan on
Antimicrobial Resistance (2015)
Framework for National Action Plan,
with 5 objectives
1. To improve awareness and understanding on
AMR
2. To strengthen the knowledge and evidence base
through surveillance and research,
3. To reduce the incidence of infection through
effective sanitation, hygiene and infection
prevention,
4. To optimize the use of antimicrobial medicines for
human and animal health,
5. To develop the economic case for sustainable
investment, taking into account the needs for all
countries, and to increase investment in new
medicines, diagnostic tools, vaccines and other
interventions.
World Leaders Commit To Act on
Antimicrobial Resistance, September 2016
´ Antimicrobial Resistance included
in the UN Agenda for Sustainable
Development.
´ One Health
´ Human Health
´ Animal health
´ Environmental Health
´ http://www.un.org/
sustainabledevelopment/blog/
2016/09/world-leaders-commit-toact-on-antimicrobial-resistance
What lessons learnt from other priority
international agenda ?
´ Millennium Development Goals (MDG)
´ Non achievement of target in neonatal mortality
´ Non achievement of target in maternal mortality
´ What lessons learnt ?
´ Sense of ownership ?
´ Inter sector collaboration & everybody responsibility meaning nobody
responsibility
´ Quality of patient care at community and health facility levels ?
Success story (1)
Antibiotics Smart Use Program in Thailand
´ Collaborative project supported by Thai FDA and WHO, involving 80 hospitals
and health centers, started in 2007.
´ Promote rational use of antibiotics
´ “No antibiotics for non-bacterial infection”
´ Research and advocacy
´ URI, acute diarrhea and simple wound.
´ Principles
´ Bottom up approach
´ Multi facet intervention
´ Inter sectors collaboration
´ Behavioral changes
STRAMA SWEDEN
Strategic Program Against Antimicrobial
Resistance
´ Started in 2007 involving 21 subnational
health authorities
´ At the national level
´ National Board of Health and Welfare
(national regulatory body)
´ Swedish Institute for Infectious Disease control
´ STRAMA group
´ STRAMA at the local level
´ Clinical microbiology
´ Infections control
´ Clinic for infectious diseases
´ Mandatory drug committee
´ Country medical officer.
´ Consensus & problem solving solution
Monitoring antibiotic consumption
(DDD/1000 population)
INRUD – International Network for Rational Use of
Drugs
´ Mission - Planning and testing
intervention on Rational Use of Medicines
´ INRUD network 30 groups from Asia,
Africa, Latin America, Eastern Europe
and WHO
´ Harvard Medical School, Karolinska
Institutet, University of Boston,
´ Secretariat Management Sciences for
Health (MSH) di USA.
´ Launched in Yogyakarta, 1989
J Quick, B Santoso D. Bimo, Ross Degnan,
R Laing, KK Kafle, Azad Choudhury,
David Ofori Adjei, Biola Mabadeje etc.
Indonesia contribution
´ Interactive Group Discussion
involving providers and
consumers (IGD)
´ Mothers Active Learning Module
for critical assessment of ads
(CBIA)
´ MTP (monitoring training and
planning ) – micro-level instrument
to improve quality use
(MSH)
What are the way forwards?
´ Whole society engagement
´ Prevention first
´ Access
´ Sustainability
´ Incremental target for
improvement
WHO, 1915
´ Focused on actions
implementation at subnational/
hospital/community levels
´ Strengthen surveillance of high risk
conditions
´ Networking between referral
hospitals and districts hospitals
´ Community education on drugs/
antimicrobials.
´ National coordination mechanism
Thank you so much
CONTAINING
ANTIMICROBIAL RESISTANCE
Budiono Santoso
International Network for Rational Use of Drugs (INRUD) – Indonesia,
Gadjah Mada University MedicaL Alumni Association
Personal background & introduction
Professionals in
medicines area
- INRUD
- US Pharmacopeia
- IUPHAR Clinical
Pharmacology
- WHO Expert
Committee
Clinical
Pharmacologist
Academician &
researcher
Gadjah Mada
University
1977 - 1999
Former Team Leader
in Pharmaceuticals &
Health Technology
WHO Western Pacific
Regional Office
1999 - 2013
ANTIMICROBIAL RESISTANCE
What are the issues ?
´ Increasing incidence of resistance
´ Antibiotics
´ Anti parasitic
´ Antifungals
´ Anti HIV/AIDS
´ Well documented in different
settings, both developed and
developing countries.
´ Different levels of awareness and
commitment
SILENT EPIDEMICS
with
serious impact on
health
Leading infectious killers, global, millions of
deaths (WHO surveillance 1998)
´ Malaria - choroquine resistance in
81/92 countries
4
´ Tuberculosis : 0-22 % primary MDR
´ HIV/AIDS : 0-25 % primary
3.5
resistance to at least one antiretroviral
3
2.5
´ Pneumonia and bacterial
meningitis
2
1.5
´ 0-70 % penicillin resistance
S.pneumoniae
1
´ Diarrhoea: shigellosis
0.5
0
ARI
AIDS
Diarrhoeal
diseases
TB
Malaria
´ 10-90% ampicillin resistance
´ 5-95% cotrimoxazole resistance
´ Hospital infections : 0-70% S.
Aureus resistance to all penicillins &
cephalosporins
Global Surveillance report 2014
´
Jeopardizing the future treatment of
“ ….. The data reviewed for the
report reveals serious problems and
worsening trends in antimicrobial
resistance in some nations in the
Southeast Asian region”.
´ Pneumonia and meningitis
´ Shigellosis
´ Sepsis including neonatal sepsis
´ Hospital infections
´ Urinary tract infections
´ Post surgery infections
´ Gonorrhea
´ Malaria
´ TB
´ Cancer chemotherapy
´ Major surgery, etc
Antimicrobial Resistance WHO Global surveillance report 2014
E Coli
Resistance to 3rd generation
cephalosphorins
Klebsiella pneumoniae
Resistance to 3rd generation
cephalosporins
Staphylococcus aureus:
Resistance to methicilline
(MRSA)
Streptococcus pneumoniae:
Resistance, or nonsusceptibility, to penicillin
Shigella species:
Indonesia
(%)
10 (ctx)
13.8 (cro)
53.3 (ctx);
67.2 (cro)
-
Malaysia
(%)
Thailand (%)
Philippines
(%)
14.9 (caz);
18 (cro);
20 (ctx)
30.5 (caz);
41.4 (cro);
42.7 (ctx)
26.7
37.4 (caz);
40.3 (cro);
41.1 (ctx)
30
21.1 (cro);
20.8 (caz);
24 (ctx)
17.3
21.6 (cef);
24.2 (oxa)
54.9
-
17.5
47
43
-
2.9
76
44.4
Antimicrobial resistance in Indonesia
( AMRIN STUDY, 2000 – 2005)
Community infections
( n = 2494)
´ E Coli Resistance (43%)
´ E Coli Resistance ( 81 %)
´ Ampicillin
- 34 %
´ Ampicillin
- 73 %
´ Co-trimoxazole
- 29 %
´ Co-trimoxazole
- 56 %
´ Chloramphenicol - 25 %
MOH, 2015
Hospital infections
( n = 781 )
´ Chloramphenicol - 43 %
´ Cyprofloxazine
- 22 %
´ Gentamycin
- 18 %
Antimicrobial Resistance –
What could be the impacts ?
Prolonged
Treatment &
Treatment failure
increased
morbidity &
Mortality
Escalating
healthcare cost
& reduced
access and
coverage
Potential loss of
effective therapy in
the future
Cost ratio of alternative drugs to 1st line antimicrobials:
2nd, 3rd, and 4th line drugs may be 2 to 90 times costlier
Cost ratio to
1st line drug
80
70
60
50
Alternative
drugs
4th
40
30
20
3rd
10
2nd
0
Gonorrhoea
Malaria
Shigellosis
Pneumonia
Cost per
0.03 US$
0.05 US$
0.06 US$
0.14 US$
patient with 1st
line drug Source: WHO model formulary and relevant WHO clinical guidelines on the WHO website
2004, and Management Sciences for Health's 2004 International Drug Price Indicator
Guide
World Health Organization
Essential Medicines and Pharmaceutical Policy
Survival after pneumococcus pneumoniae with
sepsis before and after the discovery of penicillin
WHO, 2014
Antimicrobial Resistances
Possible risk factors
Overuse,
indiscriminate
use, underdosage by
providers and
consumers
Uncontrolled
distribution of
antimicrobials
The use of
antimicrobials for
human in
veterinary and
agricultures
Substandard
quality of
antimicrobials
products
60
Penicillin-resistant S. pneumoniae (%)
Taiwan
50
Spain
France
40
USA
Greece
30
Portugal
Ireland
20
Austria
Canada
Luxemburg
Iceland
Italy
Belgium
UK
Australia
Germany
Finland
Sweden
Albrich, Monnet and Harbarth,
Denmark
Emerg Infect Dis.; 2004; 10(3):514-7
Netherlands
Norway
10
0
0
10
20
30
40
Total antibiotic use (DDD/1000 population/day)
World Health Organization
Essential Medicines and Pharmaceutical Policy
Antimicrobial Resistance
What need to be done ?
´ Improve AMR monitoring and surveillance
´ Enforce regulation
´ Quality production of antimicrobial products
´ Quality surveillance
´ Controlled distribution
´ Quality use of antimicrobials
´ Antimicrobials usage surveillance
´ Antibiotic policy as part of national medicines policy
´ Advocacy and information for providers and consumers
´ One Health approach - Use of antimicrobials in veterinary and agriculture
Antimicrobial resistance
What have been done at global, regional and
national levels?
´ Global & regional levels
´ Intercountry consultation at regional and global level
´ Inter-partners consultation – donors, industries, non governmental institutions, academic institutions.
´ WHO Global Strategy for Containment of Antimicrobial Resistance, 2001
´ WHO Global Action on Antimicrobial Resistance 2015
´ National level
´ National training & workshop on AMR
´ National action plan for Containment of Antimicrobial Resistance.
´ Subnational/institutional/hospital levels
´ Implementing relevant actions : surveillance, RDU, hospital policy etc ?
´ Community levels
´ Public education and advocacy ?
WHO Global Strategy for Containment
of Antimicrobial Resistance 2001
National Task Force to coordinate 67 interventions in
six key areas
1. Strengthen surveillance capabilities
2. Improve use of antimicrobials
3. Improve access to appropriate antimicrobials
4. Reduce disease burden & spread of infection
5. Enforce regulations & legislation
6. Develop appropriate new drugs & vaccines
WHO Global Action Plan on
Antimicrobial Resistance (2015)
Framework for National Action Plan,
with 5 objectives
1. To improve awareness and understanding on
AMR
2. To strengthen the knowledge and evidence base
through surveillance and research,
3. To reduce the incidence of infection through
effective sanitation, hygiene and infection
prevention,
4. To optimize the use of antimicrobial medicines for
human and animal health,
5. To develop the economic case for sustainable
investment, taking into account the needs for all
countries, and to increase investment in new
medicines, diagnostic tools, vaccines and other
interventions.
World Leaders Commit To Act on
Antimicrobial Resistance, September 2016
´ Antimicrobial Resistance included
in the UN Agenda for Sustainable
Development.
´ One Health
´ Human Health
´ Animal health
´ Environmental Health
´ http://www.un.org/
sustainabledevelopment/blog/
2016/09/world-leaders-commit-toact-on-antimicrobial-resistance
What lessons learnt from other priority
international agenda ?
´ Millennium Development Goals (MDG)
´ Non achievement of target in neonatal mortality
´ Non achievement of target in maternal mortality
´ What lessons learnt ?
´ Sense of ownership ?
´ Inter sector collaboration & everybody responsibility meaning nobody
responsibility
´ Quality of patient care at community and health facility levels ?
Success story (1)
Antibiotics Smart Use Program in Thailand
´ Collaborative project supported by Thai FDA and WHO, involving 80 hospitals
and health centers, started in 2007.
´ Promote rational use of antibiotics
´ “No antibiotics for non-bacterial infection”
´ Research and advocacy
´ URI, acute diarrhea and simple wound.
´ Principles
´ Bottom up approach
´ Multi facet intervention
´ Inter sectors collaboration
´ Behavioral changes
STRAMA SWEDEN
Strategic Program Against Antimicrobial
Resistance
´ Started in 2007 involving 21 subnational
health authorities
´ At the national level
´ National Board of Health and Welfare
(national regulatory body)
´ Swedish Institute for Infectious Disease control
´ STRAMA group
´ STRAMA at the local level
´ Clinical microbiology
´ Infections control
´ Clinic for infectious diseases
´ Mandatory drug committee
´ Country medical officer.
´ Consensus & problem solving solution
Monitoring antibiotic consumption
(DDD/1000 population)
INRUD – International Network for Rational Use of
Drugs
´ Mission - Planning and testing
intervention on Rational Use of Medicines
´ INRUD network 30 groups from Asia,
Africa, Latin America, Eastern Europe
and WHO
´ Harvard Medical School, Karolinska
Institutet, University of Boston,
´ Secretariat Management Sciences for
Health (MSH) di USA.
´ Launched in Yogyakarta, 1989
J Quick, B Santoso D. Bimo, Ross Degnan,
R Laing, KK Kafle, Azad Choudhury,
David Ofori Adjei, Biola Mabadeje etc.
Indonesia contribution
´ Interactive Group Discussion
involving providers and
consumers (IGD)
´ Mothers Active Learning Module
for critical assessment of ads
(CBIA)
´ MTP (monitoring training and
planning ) – micro-level instrument
to improve quality use
(MSH)
What are the way forwards?
´ Whole society engagement
´ Prevention first
´ Access
´ Sustainability
´ Incremental target for
improvement
WHO, 1915
´ Focused on actions
implementation at subnational/
hospital/community levels
´ Strengthen surveillance of high risk
conditions
´ Networking between referral
hospitals and districts hospitals
´ Community education on drugs/
antimicrobials.
´ National coordination mechanism
Thank you so much