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 meta micro patient population 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

EARSS database

EARSS database

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 Penicillin Cefoxitin Ciprofloxacin Gentamicin Tobramycin Erythromycin Clindamycin Tetracycline Fusidic Acid Linezolid Rifampicin Teicoplanin Vancomycin Total: 131 216 219 243 79 260 172 133 175 194 225 87 118 2252 5 1 4 3 1 8 10 1 7 3 4 1 1 49 94,7 98,6 98,2 99,6 98,7 96,9 94,2 99,2 97,1 99,5 98,2 96,6 99,2 97,8 308 308 308 308 308 308 308 308 308 308 308 120 120 3628 1 0 1 3 0 7 4 5 0 7 8 5 1 42 97,7 98,7 98,4 100,0 97,7 97,4 98,4 99,7 99,7 100,0 99,7 97,5 100,0 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)