General Aspects of Antibacterial Resistance
Surveillance
Hajo Grundmann
University Medical Centre Groningen
ReAct – Action on Antibiotic Resistance
Topics
•
Surveillance: general considerations
•
The three levels of ABR surveillance
•
Threats to validity and solutions
General considerations
Definition: Surveillance
‘ The ongoing systematic collection, analysis of health data
essential to the planning, implementation, and evaluation, of
public health practice, …
Alexander Langmuir 1963
The ecological landscapes of AMR surveillance
Microbiota
Patients
Antibiotic
Exposure
The Nemesis of good surveillance in
Antibiotic resistance
•
Ambition
•
Perfection
•
Conflicting demands
The Demands: who defines them?
Stakeholders
•
Individuals who are directly affected
•
Individuals who indirectly suffer from the
repercussions of adverse health care outcomes
caused by ABR
•
Individuals who have a professional, corporate
or altruistic responsibility
The three levels of ABR surveillance
macro
patient
meta
population
micro
pathogen
Patient level surveillance
Patient level surveillance
Objective
•
Optimising empirical antibiotic therapy
Scale and Scope
•
Local (single institution), timely, syndrome-based, inclusive
Metric (operational unit of surveillance)
•
Proportion resistance per infection and antibiotic compound
based on the resistance among the causative pathogens
(stratified by ethological fraction)
see drug effectiveness index
Ciccolini et al. JAC (2014)
Population level surveillance
Population level surveillance
Objective
•
Estimating the size of ABR as a national and international
public health problem
Scale and Scope
•
laboratory-based passive surveillance at selected sentinel
sites using routinely available data
Metric (operational unit of surveillance)
•
Proportion resistance per indicator pathogen and antibiotic
class for primary bacterial isolates (SPY criteria) from
defined anatomical sites
EARSS 2008
917 Laboratories
1587 Hospitals
>100 million citizens
33 countries
EARSSdatabase
EARSSdatabase
Pathogen level surveillance
Pathogen level surveillance
Objective
•
Identifying the orgin, emergence and transmission of
bacterial pathogens and their high risk clones (HiRiCs)
Scale and Scope
•
laboratory-based genomic analysis of bacterial isolates
Metric (operational unit of surveillance)
•
measure of the genetic distance between any two bacterial
isolates determined by high resolution genomic analysis
Threats to validity and solutions
Threats to validity and solutions
Representativeness
•
How many sites do you need to include to
determine ABR at national level?
Data quality
•
How do you make sure that you could trust the
data?
How many sites do you need to include ?
The HCU network
The “greedy” network
Ciccolini et al, PNAS (2014)
How do you make sure that you can trust the data?
Sentinel laboratories must
• adhere to agreed laboratory protocols incl. quality control,
• use agreed clinical susceptibility breakpoints (CLSI or
EUCAST)
• have in place an acceptable laboratory information
management system (WHO-NET)
• have a dedicated data manager
• participate in national/international quality assessment
schemes (EQA)
How do you make sure that you can trust the data?
S. aureus AST results against Gold Standard in single laboratory
Comparison of SRL and EUCAST
Comparison of in silico and EUCAST
Antibiotic Total no. testsDiscordance% concordance
Total no. testsDiscordance% concordance
Penicillin
131
7
94,7
308
7
97,7
Cefoxitin
216
3
98,6
308
4
98,7
Ciprofloxacin
219
4
98,2
308
5
98,4
Gentamicin
243
1
99,6
308
0
100,0
Tobramycin
79
1
98,7
308
7
97,7
Erythromycin
260
8
96,9
308
8
97,4
Clindamycin
172
10
94,2
308
5
98,4
Tetracycline
133
1
99,2
308
1
99,7
Fusidic Acid
175
5
97,1
308
1
99,7
Linezolid
194
1
99,5
308
0
100,0
Rifampicin
225
4
98,2
308
1
99,7
Teicoplanin
87
3
96,6
120
3
97,5
Vancomycin
118
1
99,2
120
0
100,0
Total:
2252
49
97,8
3628
42
98,8
ask every sentinel laboratory to perform whole genome sequencing
on all indicator isolates!
Thanks
UMCG
Mariano Ciccolini
Tjibbe Donker
ECDC
Liselotte Hornberg Diaz
Ole Heuer
Sanger Centre
Matt Holden
David Aanensen
EUCAST Development Laboratory,Växjö, Sweden
Jenny Ahmann
Erika Matuscheck
Gunnar Kahlmeter
United Kingdom Clinical Research Collaboration (UK CRC)