Surveillance von Antibiotikaresistenzen: Wünsche und Wirklichkeit

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Surveillance von Antibiotikaresistenzen: Wünsche und Wirklichkeit

Surveillance von

Antibiotikaresistenzen:

Wünsche und Wirklichkeit

Hajo Grundmann

National Institute for Public Health and the

Environment (RIVM)

Bilthoven, NL


Topics






what are the demands?

how can they be met?

what weaknesses remain?

examples

Resumee & Outlook


Demands 1


Patients

– informing efficacious empirical treatment with

optimal side effect profile


Practitioners

– clinically relevant

– timely

– regional


Demands 2


Microbiologists

– species-specific

specific

– valid

– comparable


Pharmaceutical Industry

– substance-specific

specific

– syndrome-specific

specific


Demands 3


Policy Makers

– causal relatedness


Public Health Specialists

– population-based

– supraregional

– open to trend analysis

– stratifiable


Interested Public

– communicable

– educative


Meeting the demands from patients and

practitioners


Local laboratory = centre of local expertise


Feedback of resistance rates on local level (hospital

laboratory data base)


Weaknesses: limited testing of clinical samples of the

most common infections


Example: EcoSense network


Meeting the demands of Microbiologists


Meeting the demands of pharmaceutical

industry


Tailor-made surveillance networks


Meeting the demands of policy makers

❑ Causal relatedness

– antibiotic consumption

ESAC, ARPAC, SARI, STRAMA


Meeting the demands of policy makers

❑ Causal relatedness

– antibiotic consumption

ESAC, ARPAC, SARI, STRAMA

– infection control measures

ARPAC


Meeting the demands of policy makers

❑ Causal relatedness

– antibiotic consumption

ESAC, ARPAC, SARI, STRAMA

– infection control measures

ARPAC

– per capita GNP


MRSA incidence and GDP (2003)

MRSA isolates per 100,000 patient

days

16

14

12

10

8

East Europe: 6

BG, HR, RO, EE, PL,

HU, CZ, SK, SI 4

2

0

UK

South Europe:

MT, PT, IL, ES, FR

North Europe:

SE, FI, IS, NL

0 10,000 20,000 30,000 40,000 50,000

gross domestic product per capita (USD)

LU


Meeting the demands of public health

specialists

❑ How to reconcile resistance proportions with

incidence among the population at risk ?


MRSA incidence and proportion

MRSA incidence (per 100,000 patientdays)

16

14

12

10

8

6

4

2

0

PL

0% 10% 20% 30% 40% 50%

MRSA proportion

BG

PT

HR

R 2 =0.92

RO


Meeting the demands of public health

specialists

❑ How to reconcile resistance proportions with

incidence among the population at risk ?

❑ Does aggregating data on supraregional level

make sense?


Geographic

distribution


Meeting the demands of public health

specialists

❑ How to reconcile resistance proportions with

incidence among the population at risk ?

❑ Does aggregating data on supraregional level

make sense?

❑ Trend analysis needs consistency!


Meeting the demands of public health

specialists

❑ How to reconcile resistance proportions with

incidence among the population at risk ?

❑ Does aggregating data on supraregional level

make sense?

❑ Trend analysis needs consistency!

❑ Stratification as a means to identify alternative

explanations!


Blood culturing and GDP (2003)

number of blood cultures/1000

patient-days

50

40

30

20

10

0

R 2 = 0.8078

0 5,000 10,000 15,000 20,000 25,000

gross domestic product per capita ($), 1998


Prolongation of infectiousness

Case reproduction numbers

Rn 2

1.8

1.6

1.4

1.2

1

0.8

0.6

0.4

0.2

0

5 10 15 20 25 30 35

13.6 days

Length of stay


Does resistance matter ?



morbidity

– prolonged disease

– prolongation of infectiousness

– increased cost

mortality

– MRSA was the single most important predictor for

mortality from pneumonia and primary septicaemia in

the KISS study 286 ICUs in Germany


Can surveillance make a difference?







raises awareness

provides robust figures rather then a vague

feeling

brings AB-resistance on the public health

agenda

can be embarrassing

engenders a rethinking on AB-use in humans

and animals

may act as a disincentive for industries


The surveillance cycle

surveillance

feedback

intervention


EARSS = European Antimicrobial

Resistance

Surveillance System

funded by DG-SANCO of the European

Commission

endorsed by European Parliament and the Council

Legislation 2119/98/EC and Commission Decision

2000/96/EC


Mission

It is the remit of EARSS to maintain a

comprehensive surveillance and information

system that links national networks by

providing comparable and validated data on the

prevalence and spread of major invasive

bacteria with clinically and epidemiologically

relevant antimicrobial resistance in Europe.


Mission

It is the remit of EARSS to maintain a

comprehensive surveillance and information

system that links national networks by

providing comparable and validated data on the

prevalence and spread of major invasive

bacteria with clinically and epidemiologically

relevant antimicrobial resistance in Europe.


Mission

It is the remit of EARSS to maintain a

comprehensive surveillance and information

system that links national networks by

providing comparable and validated data on the

prevalence and spread of major invasive

bacteria with clinically and epidemiologically

relevant antimicrobial resistance in Europe.


Mission

It is the remit of EARSS to maintain a

comprehensive surveillance and information

system that links national networks by

providing comparable and validated data on the

prevalence and spread of major invasive

bacteria with clinically and epidemiologically

relevant antimicrobial resistance in Europe.


Mission

It is the remit of EARSS to maintain a

comprehensive surveillance and information

system that links national networks by

providing comparable and validated data on the

prevalence and spread of major invasive

bacteria with clinically and epidemiologically

relevant antimicrobial resistance in Europe.


Mission

It is the remit of EARSS to maintain a

comprehensive surveillance and information

system that links national networks by

providing comparable and validated data on the

prevalence and spread of major invasive

bacteria with clinically and epidemiologically

relevant antimicrobial resistance in Europe.


Partnership

= Devolution

❑ ownership

❑ support network development

❑ support data management

❑ support microbiological protocols


Acceptability

= Restriction

❑ routine data

❑ four pathogens

❑ invasive isolates

❑ indicator antibiotics


Epidemiological Paradigms /

Generalisations

Species

Habitat

Driving Force

Population

S. pneumoniae

Man

Selection +

transmission

Community

S. aureus

Man

Transmission

Hospital

E. coli

Man +

Livestock

Emergence +

Selection

Community

E. faecium

E. fecalis

Man +

Livestock

Tansmission +

Selection

Hospital


Validity & Comparability

❑ Standard protocols

❑ annual external quality assurance exercises


Representativeness

❑ Over 700 Laboratories

❑ 28 Countries

❑ estimated 100 million population


28 Participating countries

Austria

Croatia

Estonia

Germany

Ireland

Italy

Netherlands

Portugal

Slovakia

United Kingdom

Belgium

Czech republic

Finland

Greece

Iceland

Luxembourg

Norway

Romania

Spain

Bulgaria

Denmark

France

Hungary

Israel

Malta

Poland

Slovenia

Sweden


Tangible results


Penicillin non-susceptible

S. pneumoniae (PNSP) in EU


Methicillin resistant S. aureus (MRSA)

100-fold differences!


Fluoroquinolone resistant E. coli

25%

20%

2001

2002

2003

% resistant

15%

10%

*

*

*

*

*

5%

*

0%

AT BE BG CZ DE FI HR HU IL LU MT PL SE SI SK

Country


Fluoroquinolone resistant E. coli

25%

20%

2001

2002

2003

% resistant

15%

10%

*

*

*

*

**

5%

*

0%

AT BE BG CZ DE FI HR HU IL LU MT PL SE SI SK

Country


Non-tangible results


EARSS provides

❑ partnership and not league tables


English Premiership 2002

1

Manchester United

11

Southamton

2

Arsenal

12

Charlton

3

Newcastle

13

Birmingham

4

Chelsea

14

Aston Villa

5

Liverpool

15

Fulham

6

Everton

16

Leeds

7

Blackburn

17

Bolton

8

Manchester City

18

West Ham

9

Tottenham

19

West Brom

10

Middlesbrough

20

Sunderland


Another League

80

70

60

50

40

30

20

10

Coronary heart attacks in Europe (per 10,000)

0

UK FI NO IE DK CZ IS SE BE PT SL AU DE GR IT NL ES


EARSS provides

❑ partnership and not league tables

❑ incentive for the implementation of national

networks

❑ impulse for standardisation of protocols

❑ ecological outcome indicators for AB-consumption

and transmission


Scientific spin off

understanding the ecology of AB-resistance


Beta lactam usage (O. Cars, , Lancet) vs.

logodds of PNSP resistance

1,00

0,00

ES

ln (R/(1-R))

-1,00

-2,00

UK

IE

LU

BE

IT

PT

-3,00

SE

FI

-4,00

NL

DE

-5,00

0 5 10 15 20 25

DDD beta-lactam antibiotics/1000 population/d

S. Bronzwaer et al., Emerg Inf Dis 2002, 8:278-82


MRSA proportion from blood cultures in Europe

Low

Intermediate

High

> 1% 1 – 24% > 25%

Denmark

Finland

Netherlands

Sweden

Austria

Belgium

Czech Rep.

Estonia

Germany

Luxemburg

Slovenia

Bulgaria

Greece

Ireland

Italy

Malta

Portugal

UK

stable

5/7 increasing 2/7 levelling off


Epidemic expansion of MRSA in the UK

Proportion MRSA from blood cultures in the UK

0,6

prop. MRSA

0,4

0,2

0

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002

year


Epidemic expansion of MRSA in the UK

Proportion MRSA from blood cultures in the UK

0,6

prop. MRSA

0,4

0,2

0

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002

year

N

K

R n = R 0 · (1- )


What determines the carrying capacity for

MRSA ?

! Fitness trade off in hospital MRSAs is considerable

! SCCmec

+ve

organisms grow slower

! SCCmec

I, II, III consist of 35 to 60kb DNA

! All have been acquired 7 times before 1990

! SCCmec

IV (21-24kb) 24kb) has been acquired 9 times

! All but once in the 90’s

! All community MRSA have SCCmec

IV


Future initiatives

❑ early warning system for the emergence and

spread of bacterial clones of particular public

health importance

❑ typing and electronic feedback


National representatives EARSS

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