General Aspects of Antibacterial Resistance General Aspects of Antibacterial Resistance SurveillanceSurveillance
Hajo Grundmann
University Medical Centre GroningenReAct – Action on Antibiotic Resistance
TopicsTopics
• Surveillance: general considerations
• The three levels of ABR surveillance
• Threats to validity and solutions
General considerationsGeneral considerations
Definition: SurveillanceDefinition: 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 surveillanceThe ecological landscapes of AMR surveillance
Patients Antibiotic Exposure
Microbiota
The Nemesis of good surveillance in The Nemesis of good surveillance in Antibiotic resistanceAntibiotic resistance
• Ambition
• Perfection
• Conflicting demands
The Demands: who defines them?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 surveillanceThe three levels of ABR surveillance
macro
meta
micro
patient
population
pathogen
Patient level surveillancePatient level surveillance
Patient level surveillancePatient 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 surveillancePopulation level surveillance
Population level surveillancePopulation 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 2008EARSS 2008
917 Laboratories917 Laboratories
1587 Hospitals1587 Hospitals
>100 million citizens>100 million citizens
33 countries33 countries
EARSS-database
EARSS-database
Pathogen level surveillancePathogen level surveillance
Pathogen level surveillancePathogen 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 solutionsThreats to validity and solutions
Threats to validity and solutionsThreats 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 HCU network
The “greedy” network The “greedy” network
Ciccolini et al, PNAS (2014)
How do you make sure that you can trust the data? 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? How do you make sure that you can trust the data?
ask every sentinel laboratory to perform whole genome sequencing on all indicator isolates!
Antibiotic Total no. testsDiscordance% concordanceTotal no. testsDiscordance % concordancePenicillin 131 7 94,7 308 7 97,7Cefoxitin 216 3 98,6 308 4 98,7Ciprofloxacin 219 4 98,2 308 5 98,4Gentamicin 243 1 99,6 308 0 100,0Tobramycin 79 1 98,7 308 7 97,7Erythromycin 260 8 96,9 308 8 97,4Clindamycin 172 10 94,2 308 5 98,4Tetracycline 133 1 99,2 308 1 99,7Fusidic Acid 175 5 97,1 308 1 99,7Linezolid 194 1 99,5 308 0 100,0Rifampicin 225 4 98,2 308 1 99,7Teicoplanin 87 3 96,6 120 3 97,5Vancomycin 118 1 99,2 120 0 100,0
Total: 2252 49 97,8 3628 42 98,8
Comparison of SRL and EUCAST Comparison of in silico and EUCAST
S. aureus AST results against Gold Standard in single laboratory
ThanksThanksUMCGMariano CiccoliniTjibbe Donker
ECDCLiselotte Hornberg DiazOle Heuer
Sanger CentreMatt HoldenDavid Aanensen
EUCAST Development Laboratory,Växjö, SwedenJenny AhmannErika MatuscheckGunnar Kahlmeter
United Kingdom Clinical Research Collaboration (UK CRC)