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The German AMR Strategy,
One Health - Global Health
Lothar H. Wieler
Robert Koch Institute
PAC 11 Side-Event
From strategies to action – Adressing the challenges of AMR in the Northern Dimension Area
Berlin, Germany 19 November 2015
DART (2008 – 2014)
German strategy against antibiotic resistance
Strategy of
• the Federal Ministry of Health
• the Federal Ministry of Food and Agriculture
• the Federal Ministry of Education and Research
DART (2008 – 2014)
10 national aims in 4 components:
• Surveillance-systems for antimicrobial
resistance and antimicrobial use
• Prevention and control measurements to
reduce antimicrobial resistance
• Cooperation and coordination
• Research and evaluation
Antimicrobial Resistance Surveillance (ARS)
Strengthening the surveillance system
• Antimicrobial Resistance Surveillance (ARS)
is a laboratory-based sentinel surveillance system
with continuous collection of data on antimicrobial
resistance for the entire spectrum of clinically
relevant bacterial pathogens for both inpatient and
outpatient care at national level.
• The major objective is to provide reference data for
public use and specific feedback for participating
laboratories.
The organisation involved in the project:
Robert Koch Institute https://ars.rki.de/
Timescale: ongoing
Antimicrobial Resistance Surveillance (ARS)
Strengthening the surveillance system
?
Antimicrobial Resistance Surveillance (ARS)
Strengthening the surveillance system
Surveillance of antibiotic consumption (AVD)
Strengthening the surveillance system
The objectives of the project are:
• to provide an electronic automated system for the collection, analysis and
reporting of antibiotic consumption data in the hospital sector.
• to support the hospitals in the conduct of antibiotic
• consumption surveillance and local antibiotic stewardship efforts
• to build up a national database as a basis for the provision of reference data.
• 120 hospitals registered, 45 reported data
Timescale: Start of the project: 2013.
Pilotphase: 08—12, 2014.
Routine phase: since 2015
The organisation involved in the project:
Robert Koch Institute, Dep. 3, FG37
www.rki.de
Webside project: https://avs.rki.de
NEO-KISS
Strengthening the surveillance system
• NEO-KISS (nosocomial infection surveillance system for preterm infants on
neonatology departments and ICUs) is a mandatory national surveillance system for
nosocomial infections in very low birth weight infants in Germany.
All children with a birthweight of less
than 1500 g are included until their hospital
discharge, death or weight of over 1800 g.
Specially developed definitions are used for
the diagnosis of the three kinds of infections:
pneumonia, primary bloodstream infections,
and necrotizing enterocolitis.
Timescale: Start: 2006, ongoing
The organisation involved in the project:
National Reference Center for Nosocomial Infection
Surveillance
http://www.nrz-hygiene.de/surveillance/kiss/neo-kiss/
NEO-KISS
Strengthening the surveillance system
Hospital antibiotic stewardship (ABS)
expert training and network initiative
Promote the responsible use of antibiotics
•
•
To increase the number of physicians and pharmacists with
knowledge and skills in rational prescribing and strategic
antibiotic stewardship activities in acute care hospitals.
To establish a stewardship expert network for exchange of
experience, for continuous education, and as forum for
cooperative quality improvement projects
Timescale: 2010—2013
and 2014—2017
Photo: picture-alliance/dpa/Bernd Wüstneck
The organisations involved in the project:
Abteilung Infektiologie, Universitätsklinikum Freiburg,
Abteilung Infektiologie, Universitätsklinikum Dresden
DGI www.dgi-net.de
ABS-Expertennetzwerk www.antibiotic-stewardship.de
Aktion “Saubere Hände” (Clean Hands)
Combating and preventing infections
• “Aktion Saubere Hände” (Clean Hands) is a national campaign for improvement of
compliance to hand disinfection in German healthcare facilities
• Based on the WHO campaign “Clean Care is Safer Care” that started in 2005.
• It supports implementation of multimodal infection control interventions.
The organisation involved in the project:
German National Reference Center for Surveillance of
Nosocomial Infections
Coalition for Patient Safety
Timescale: 2008—ongoing
MRSA-Net and Regional MRSA/MDR Networks
Promote the responsible use of antibiotics
• Reduction of MRS (MDR) load in the ambulatory, hospital and nursing home setting
by increasing the implementation of guidelines and communication in stakeholder
networks.
The organisation involved in the project:
regional and local health offices
MRSA-Net http://www.mrsa-net.nl/de/
Regional MRSA/ MDR Networks (Germany)
http://www.rki.de/DE/Content/Infekt/
Krankenhaushygiene/Netzwerke/Netzwerke_node.htm
Timescale: since 2005
GERMAP
Strengthening the One Health approach
• Provides a summary of data on the consumption of
antimicrobials and the extent of resistances against
antimicrobials in human and veterinary medicine.
It is compiled by an expert group from human and
veterinary medicine and is updated every second year.
It is a basis for risk assessment and supports the
development of treatment-guidelines for both
humans and animals.
Timescale: 2008, ongoing
The organisations involved in the project:
- Bundesamt für Verbraucherschutz und Lebensmittelsicherheit
Dienstsitz Berlin
- Paul-Ehrlich-Gesellschaft für Chemotherapie
- Infektiologie Freiburg, Medizinische Universitätsklinik Zentrum
Infektiologie und Reisemedizin
Research Area “Antimicrobial
Resistance and Nosocomial Infections”
Support of research and development
• Supporting research and development is one goal of the German Antimicrobial
Resistance Strategy “DART 2020”.
• The research area “Antimicrobial Resistance, Hygiene and Nosocomial Infections”
supports its implementation.
Within this activity 11 projects out of four thematic areas
were funded over a period of three years.
The projects include results-based intervention studies, the
training of specialist staff, model projects for inter-sectoral
health care, and the further development of quality
assurance.
Timescale: 2012—2015
The organisation involved in the project:
German Federal Ministry of Health
http://www.bmg.bund.de/themen/
praevention/krankenhausinfektionen/
antibiotika-resistenzstrategie.html
Research projects:
RESET - Strengthening the One Health approach
• Collaborative project on ESBL- and (fluoro-)quinolone resistance in
enterobactericeae (RESET)
• To determine the prevalence of ESBL-producing bacteria in humans, animals, animal food
and the environment.
• To identify the respective resistance genes and analyse their transferability between
Enterobacteriaceae.
• To compare genetic relationship of bacterial isolates and resistance gene carrying
plasmids in different settings, to evaluate the transmission pathways of ESBL-resistance.
Timescale: 2011—2016
The organisation involved in the project:
Institut für Biometrie, Epidemiologie und
Informationsverarbeitung, Hannover
Research projects:
MedVetStaph - Strengthening the One Health approach
Goals:
1. To identify the risk MRSA which emerged in livestock
and companion animals pose to humans.
2. To identify the contribution of clinically relevant
antibiotic resistance genes contained by staphylococci
from animals to antibiotic resistance development in
staphylococci of human.
3. To further develop targeted antibiotic resistance
surveillance as well as strategies for diagnostics,
intervention, and therapy as one health approach.
Timescale: 2011—2016
The organisation involved in the project:
Institut für Hygiene, Dr. Robin Köck
Universitätsklinikum Münster
DART — veterinary issues
combating and preventing infections
promote the responsible use of antibiotics
• Reducing the number of antibiotic treatments of fattening animals to the inevitable
minimum by improving animal health and strengthening prudent use through legal
requirements.
The organisation involved in the project:
Legislator
Federal Ministry of Food and Agriculture
Timescale: Came into force April 1, 2014
QS Quality scheme for food:
The food industry’s own antibiotics monitoring
Strengthening the surveillance system
• Reducing the number of antibiotic treatments in
livestock to the inevitable minimum.
• Strengthening prudent use.
• In the QS system, veterinarians have to enter all relevant data
for each single antibiotic treatment of livestock into the
QS database.
• All details on this are described in specific guidelines.
• The analysis of this data by QS enables veterinarians and
livestock keepers to compare the antibiotic treatments with
the average of all farms in the QS system.
Timescale: continuing since 2013
The organisation involved in the project:
QS GmbH
https://www.q-s.de/veterinarians/antibioticsmonitoringveterinarians.html
Prescription only for antibiotics in veterinary medicine
Promote the responsible use of antibiotics
• In Germany, all antimicrobial veterinary medicinal products are available only on
prescription by a veterinary surgeon who in turn is only permitted to hand out
prescriptions to owners of animals under his or her care.
• Over-the-counter sale is prohibited.
The organisation involved in the project:
Federal Ministry of Food and Agriculture
Timescale: ongoing since many years
AMR and animal health related research
Support of research and development
• There are two major approaches for agricultural livestock farming to reduce
the exposure of consumers to resistant bacteria and their resistance
characteristics from livestock farming:
1. Reducing the occurrence of resistant bacteria in livestock farming through preventive measures to
maintain the health of animal stocks without antibiotics
2. Preventing the transmission of resistant bacteria along the food chain. The organisation involved in the project:
Federal Ministry of Food and Agriculture
and stakeholders
Timescale: next 5 years
EARS-Net Report 2014: results (overview)
EARS-Net Report 2014: results (overview)
EARS-Net Report 2014: results (overview)
MRSA trend in Germany
(mandatory reporting data)
Incidence of notified episodes of invasive methicillinresistant Staphylococcus aureus infections per 100,000
persons stratified by age, sex and year of notification in
Germany, 2010–2014 (n=20,679)
Incidence of invasive Methicillin-resistant Staphylococcus aureus infections in
Germany, 2010 to 2014
Jan Walter, Sebastian Haller, Hans-Peter Blank, Tim Eckmanns, Muna Abu Sin,
Julia Hermes (accepted Eurosurveillance)
Notified MRSA Infections (blood or CSF) per
100.000 persons by Federal State, Germany
2010 to 2014
Livestock-associated MRSA (ST398) in Veterinarians
odds ratio for LA MRSA colonization
(bars mark the 95% confidence
intervals)
Visits to swine farms and nasal colonization with livestock-associated (LA) MRSA
(clonal complex 398) among 695 veterinarians in Germany, 2008/2009
20
15
10
5
0
1
2
3-9
Number of visits to swine farms per week
Walter, Espelage, Cuny, Jansen, Witte, Eckmanns, Hermes. Clin Infect Dis Sep. 3
10+
Molecular surveillance (Whole Genome Sequencing)
Healthcare-associated outbreak - MSSA
• Berlin 2010
• Neonatal Intensive Care Unit
• HCW A did not constantly
transmit the MRSA to the
patients
U Nübel, M Nachtnebel, G Falkenhorst, J Benzler, J Hecht, M Kube, F Bröcker, K Moelling, C Bührer, P Gastmeier, B Piening, M Behnke,
M Dehnert, F Layer, W Witte, T Eckmanns, PLoS One, 2013
Molecular surveillance (Whole Genome Sequencing)
Healthcare-associated outbreak Klebsiella pneumonia (ESBL)
• Berlin current outbreak
• Acute rehabilitation clinic
with 26 intubated patients
• In time NGS analysis,
2 independent clusters
Pandemic ESBL- (CTX-M) producing E. coli ST131:
A One Health-Issue
Clinical impact:
Urinary tract infections (UTI)
Bloodstream infections (BSI)
Riley (CMI 2014); Nicolas-Chanoine (CMR 2014)
Bacterial Genomes are highly diverse:
The Maximum Common Genome (MCG) of ST131
Genome 1
• The MCG is defined as the set of
conserved genes occurring in every of
the considered genomes
• The size of the MCG changes
depending on the group looked at:
MCG
 The more related the genomes are the
bigger will be the MCG
• Genes in the MCG don't need to be
essential. Essential genes don't need to
be in the MCG, but usually the overlap
is quite big
Genome 2
Genome 3
von Mentzer et al. (Nature Genetics 2014)
Phylogeny of ST131 (n=228) from various sources
(Whole genome, Maximum likelihood, 9 non-ST131 outliers isolates to root phylogeny)
(H30Rx, Clade C)
Alan McNally et al. (submitted)
Phylogeny of ST131 (n=228) from various sources
(Maximum likelihood, core genome vs. accessory genome)
- multiple circulating clones of E. coli ST131
- each contains a fixed plasmid repertoire
- each has undergone clonal expansion
and global dissemination
The core genome alignment (BAPS clusters,
BratNextGen analysis),
CTX-M gene type, accessory gene profile cluster (KPax2).
(The accessory gene profile phylogeny is colour coded
by overlaying the accessory genome profile)
Alan McNally et al. (submitted)
DART 2020
Fighting antibiotic resistance for the good of both
humans and animals – and the environment
Strategy of
• the Federal Ministry of Health
• the Federal Ministry of Food and Agriculture
• the Federal Ministry of Education and
Research
DART 2020
• GOAL 1:
Strengthening the One Health approach nationally and
internationally
• GOAL 2:
Recognizing changes in resistance at an early stage
• GOAL 3:
Retaining and improving therapy options
• GOAL 4:
Breaking chains of infection early and avoiding infections
• GOAL 5:
Raising awareness and strengthening skills
• GOAL 6:
Supporting research and development
Global Health: Ebola and Antimicrobial Resistance in
the G7 context
•
•
•
•
The experienced Ebola crisis and the existing AMR
crisis show clearly the need for a new engagement
in Global Health
G7 offered to assist at least 60 countries to
implement the International Health Regulation
This is an excellent chance to strengthen the
health systems
and to support these countries in the development
of national AMR action plans and the
implementation of the
Global Antimicrobial Resistance Surveillance
System (GLASS)
African Network for improved
Diagnostics, Epidemiology and Management of Common
Infectious Agents (ANDEMIA)
• German Federal Ministry of Education and
Research financed African Networks; 80% of
the money (9.3 Mill €) for the African partners;
coordinated by an African partner
• Antimicrobial Resistance, One Health, support
of Surveillance Systems
Côte d’Ivoire
Burkina Faso
Democratic
Republic of Congo
South Africa
The organisation involved in the project:
Robert Koch Institute
Charité University Hospital Berlin
Timescale: start 2016 to 2021
Thank you
Unit 11
Unit 13
Unit 14
Unit 16
Unit 31
Unit 32
Unit 33
Unit 35
Unit 37
ZBS 1
JRG 1
JRG 4
P 2:
Enteropathogenic Bacteria and Legionella
Nosocomial Pathogens and Antibiotic Resistances
Hospital Hygiene, Infection Prevention and Control
Mycotic and Parasitic Agents and Mycobacteria
Data Management
Surveillance
Immunization
Gastrointestinal Infections, Zoonoses and Tropical Infections
Healthcare-associated Infections, Surveillance of Antimicrobial Resistance
and Consumption
Highly Pathogenic Viruses
Microbial Genomics
Bioinformatics
Acinetobacter baumannii – Biology of a Nosocomial Pathogen