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)