1011 sur annual ears net 2009

7/31/2019 1011 SUR Annual EARS Net 2009

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SURVEILLANCE REPORT

Antimicrobial resistancesurveillance in Europe

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Antimicrobial resistancesurveillance in Europe

Annul report of the Europen AntimicrobilResistnce Surveillnce Network (EARS-Net)

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SURVEILLANCE REPORTAntimicrobial resistance surveillance in Europe

Suggested cittion for full report:Europen Centre for Disese Prevention nd Control. Antimicrobilresistnce surveillnce in Europe 9. Annul Report of theEuropen Antimicrobil Resistnce Surveillnce Network (EARS -Net).Stockholm: ECDC; .

Cover picture istockphoto

ISBN 978-9-993-7-6

doi .9/3994

Europen Centre for Disese Prevention nd Control, .

Reproduction is uthorised, provided the source is cknowledged.


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Antimicrobial resistance surveillance in Europe SURVEILLANCE REPORT

Contents

Abbreviations and acronyms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .vii

Countries participating in EARS-Net 2009. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .ix

National institutions/organisations participating in EARS-Net . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .xi

Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3

2 Escherichia coliandStaphylococcus aureus: bad news and good news.Analysis of data from laboratories reporting continuously from 2002 to 2009 . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. Methods of nlysis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

. Limittions of the nlysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

.3 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

3 External Quality Assessment Exercise (EQA) 2009 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9

3.. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

3.. Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

3.3 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

4 EARS-Net laboratory/hospital denominator data 2009 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

4. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4. Methods. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

4.3 Prticiption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

4.4 Popultion coverge . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

4. Hospitl denomintor informtion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

4.6 Hospitl chrcteristics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

4.7 Lbortory denomintor informtion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

4.8 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

5 Antimicrobial resistance in Europe . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9

. Streptococcus pneumoniae. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

9. Staphylococcus aureus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

.3 Enterococci . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

.4 Escherichia coli. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36

. Klebsiella pneumoniae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47

.6 Pseudomonas aeruginosa . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

.7 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

Annex 1: Technical notes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

Annex 2: Country summary sheets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7


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List of tables

.: Averge numbers of Escherichia coli nd Staphylococcus aureus isoltes per country reported yerly from to 9 bylbortories prticipting continuously in EARSS/EARS-Net during this time intervl . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

3.: Escherichia coli (9448): Minimum inhibitory concentrtion (MIC) nd intended results reported by reference lbortories nd theoverll concordnce of the prticipting lbortories . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3.:Klebsiella pneumoniae (9449): Miniml inhibitory concentrtion (MIC) nd intended results reported by the reference lbortoriesnd the overll concordnce of the prticipting lbortories . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3.3: Streptococcus pneumoniae (94): Minimum inhibitory concentrtion (MIC) nd intended results reported by the referencelbortories nd the overll concordnce of the prticipting lbortories . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3.4: Pseudomonas aeruginosa (94): Minimum inhibitory concentrtion (MIC) nd intended results reported by the referencelbortories nd the overll concordnce of the prticipting lbortories . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

3.: Pseudomonas aeruginosa (94): Minimum inhibitory concentrtion (MIC) nd intended results reported by the referencelbortories nd the overll concordnce of the prticipting lbortories . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

3.6:Staphylococcus aureus (943): Minimum inhibitory concentrtion (MIC) nd intended results reported by the reference lbortoriesnd the overll concordnce of the prticipting lbortories . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

4.: Hospitl denomintor dt for 9 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

4.: Hospitl chrcteristics for 9 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

4.3: Lbortory denomintor informtion for 9. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

.: Number of invsive S. pneumoniae isoltes nd proportion of penicillin-non-susceptible (PNSP), penicillin-resistnt (PRSP),mcrolide non-susceptible (MNSP), single penicillin (PEN), single mcrolides (MACR) nd dul n on-susceptible (DUAL) isoltes, including9% confidence intervls (9% CI), reported per country in 9 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

.: Distribution of single penicillin, single mcrolides nd dul penicillin-mcrolides non-susceptibility, mong the most commonserogroups reported per country in 9 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

.3: Number of invsive S. aureus isoltes nd proportion resistnt to meticillin (MRSA) nd rifmpin (RIF), including 9% confidenceintervls (9% CI), reported per country in 9 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

.4: Number of invsive E. faecalis nd E. faecium isoltes nd proportion of high-level minoglycoside-resistnt E. faecalis nd

vncomycin-resistnt E. faecium (%R), including 9% confidence intervls (9% CI), reported per country in 9. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

34.: Number of invsive E. coli isoltes nd proportion minopenicillins, third-genertion cephlosporins, fluoroquinolones,minoglycosides nd multiresistnce (%R), including 9% confidence intervls (9% CI), reported per country in 9 . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39

.6: Number of invsive E. coliisoltes resistnt to third-genertion cephlosporins (CREC) nd proportion of ESBL positive mong theseisoltes, s scertined by the pr ticipting lbortories in 9 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39

.7: Overll resistnce nd resistnce combintions mong invsive Escherichia coli isoltes tested ginst minopenicillins,fluoroquinolones, third-genertion cephlosporins nd minoglycosides (n= 4 898) in Europe, 9 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

.8: Number of invsive K. pneumoniae isoltes nd proportion of fluoroquinolones, third-genertion cephlosporins, minoglycosidesnd multiresistnce (%R), including 9% confidence intervls (9% CI), reported per country in 9 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

.9: Number of invsive K. pneumoniae isoltes resistnt to third-genertion cephlosporins (CRKP) nd proportion of ESBL positivemong these isoltes, s scertined by the prticipting lbortories in 9. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

.: Overll resistnce nd resistnce combintions mong invsive Klebsiella pneumoniae isoltes tested ginst fluoroquinolones,third-genertion cephlosporins nd minoglycosides (n= 9) in Europe, 9 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

.: Number of invsive P. aeruginosa isoltes nd proportion of pipercillintzobctm, fluoroquinolones, ceftzidime,minoglycosides, crbpenems nd multiresistnce (%R), including 9% confidence intervls (9% CI), reported per country in 9. . . . . . . . . . 68

.: Overll resistnce nd resistnce combintions mong invsive Pseudomonas aeruginosa isoltes tested ginst t lest threentibiotic clsses mong pipercillintzobctm, ceftzidime, fluoroquinolones, minoglycosides nd crbpenems (n= 8 376) inEurope, 9 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69

List of figures

.: Yerly number of bloodstrem infections cused by Escherichia colind Staphylococcus aureus. EARSS/EARS-Net 9 (countries/98 lbortories) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

.: Proportion of third-genertion cephlosporin-resistnt Escherichia coli (CREC) nd meticillin-resistnt Staphylococcus aureus(MRSA). EA RSS/EARS-Net 9 ( countries/98 lbortories). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

.3: Combined resistnce (R) of Escherichia coli to minopenicillins, third-genertion cephlosporins, fluoroquinolones ndminoglycosides. EA RSS/EARS-Net 9 ( countries/98 lbortories) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

3.: Proportion of prticipting lbortories returning reports per country, 9 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3.: Adherence to guidelines: number of lbortories per country . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.: Number of lbortories nd hospitls reporting A MR nd/or denomintor dt in 9 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6


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4.: Proportion of smll, medium nd lrge hospitls per country, bsed on the number of beds, for ll hospitl reporting bothntimicrobil resistnce dt nd denomintor dt in 9 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

.:Streptococcus pneumoniae: proportion of invsive isoltes non-susceptible to penicillin (PNSP) in 9. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

.:Streptococcus pneumoniae: proportion of invsive isoltes non-susceptible to mcrolides in 9 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

.3:Streptococcus pneumoniae: proportion of invsive isoltes with dul non-susceptibility to penicillin nd mcrolides in 9. . . . . . . . . . . . . . . .

.4:Streptococcus pneumoniae: trend of penicillin non-susceptibility by country, 69 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

.:Streptococcus pneumoniae: trend of mcrolides non-susceptibility by country, 69 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

.6:Streptococcus pneumoniae: trend of dul non-susceptibility (penicillin nd mcrolides) by country, 69 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

.7: Distribution of serogroups nd the resistnce profile ofS. pneumoniae isoltes per serogroup in 9 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

.8:Staphylococcus aureus: proportion of invsive isoltes resistnt to meticillin (MRSA) in 9 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

.9:Staphylococcus aureus: trend of meticillin-resistnce (MRSA) by country, 6 9 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

.:Enterococcus faecalis: proportion of invsive isoltes with high-level resistnce to minoglycosides in 9 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3

.:Enterococcus faecalis: trends of high-level minoglycoside resistnce by country, 69 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33

.:Enterococcus faecium: proportion of invsive isoltes resistnt to vncomycin in 9 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34

.3:Enterococcus faecium: trends of vncomycin resistnce by country 69 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

.4:Escherichia coli: proportion of third-genertion cephlosporin resistnce in 9 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

.:Escherichia coli: proportion of invsive isoltes with resistnce to fluoroquinolones in 9 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

.6:Escherichia coli: proportion of invsive isoltes with resistnce to minoglycosides in 9 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

.7:Escherichia coli: trends of minopenicillin resistnce by country, 69 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

.8:Escherichia coli: trends of third-genertion cephlosporin resistnce by country, 69 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43

.9:Escherichia coli: trends of fluoroquinolone resistnce by country, 69 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44

.:Escherichia coli: trends of minoglycoside resistnce by country, 69 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

.: Escherichia coli: trends of combined resistnce (resistnt to fluoroquinolones, third-genertion cephlosporins ndminoglycosides) by country, 69 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46

.:Klebsiella pneumoniae: proportion of invsive isoltes resistnt to third-genertion cephlosporins in 9 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .49.3:Klebsiella pneumoniae: proportion of invsive isoltes resistnt to fluoroquinolones in 9 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49

.4:Klebsiella pneumoniae: proportion of invsive isoltes resistnt to minoglycosides in 9 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

.:Klebsiella pneumoniae: proportion of invsive isoltes resistnt to crbpenems in 9 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

.6:Klebsiella pneumoniae: trend of third-genertion cephlosporins resistnce by country, 69 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

.7:Klebsiella pneumoniae: trend of fluoroquinolones resistnce by country, 69. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

.8:Klebsiella pneumoniae: trend of minoglycosides resistnce by country, 69 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

.9: Klebsiella pneumoniae: trend of multiresistnce (third-genertion cephlosporins, fluoroquinolones nd minoglycosides) bycountry, 69 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

.3:Pseudomonas aeruginosa: proportion of invsive isoltes resistnt to pipercillintzobctm in 9 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

.3:Pseudomonas aeruginosa: proportion of invsive isoltes resistnt to ceftzidime in 9 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

.3:Pseudomonas aeruginosa: proportion of invsive isoltes resistnt to f luoroquinolones in 9 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

.33:Pseudomonas aeruginosa: proportion of invsive isoltes resistnt to minoglycosides in 9 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.34:Pseudomonas aeruginosa: proportion of invsive isoltes resistnt to crbpenems in 9 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

.3:Pseudomonas aeruginosa: trend of pipercillintzobctm resistnce by country, 69 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

.36:Pseudomonas aeruginosa: trend of ceftzidime resistnce by country, 69. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63

.37:Pseudomonas aeruginosa: trend of fluoroquinolones resistnce by country, 69 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64

.38:Pseudomonas aeruginosa: trend of minoglycosides resistnce by country, 69 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

.39:Pseudomonas aeruginosa: trend of crbpenems resistnce by country, 69 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66

.4: Pseudomonas aeruginosa: trend of multiresistnce (R to three or more ntibiotic clsses mong pipercillintzobctm,ceftzidime, fluoroquinolones, minoglycosides nd crbpenems) by country, 69 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67


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AMR Antimicrobil resistnce

AmpC Ampicillinse C

ARMed Antibiotic resistnce surveillnce ndcontrol in the Mediterrnen region

AST Antimicrobil susceptibility testing

BSAC British Society for AntimicrobilChemotherpy

BSI Bloodstrem infections

CC Clonl complex

CMY Cephmycinse

CLSI Clinicl nd Lbortory Stndrds InstituteCREC Third-genertion cephlosporin-resistnt

E. coli

CRKP Third-genertion cephlosporin-resistntK. pneumoniae

CSF Cerebrospinl fluid

DCFP Dt Check nd Feedbck Progrmme

DEFS Dt Entry & Feedbck Softwre

DG SANCO Directorte-Generl for Helth ndConsumer Protection

DIN Deutsche Industrie Norm (Germn)

DNA Deoxyribonucleic cid

EARSS Europen Antimicrobil ResistnceSurveillnce System

EARS-Net Europen Antimicrobil ResistnceSurveillnce Network

ECDC Europen Centre for Disese Preventionnd Control

ENSP Erythromycin non-susceptibleStreptococcus pneumoniae

EU Europen Union

EQA Externl qulity ssessment

ESAC Europen Surveillnce of AntimicrobilConsumption

ESBL Extended-spectrum bet-lctmse

ESCMID Europen Society of Clinicl Microbiologynd Infectious Diseses

ESGARS ESCMID Study Group for AntimicrobilResistnce Surveillnce

EUCAST Europen Committee on AntimicrobilSusceptibility Testing

FREC Fluoroquinolone-resistntE. coli

GISA Glycopeptide intermedite-resistntStaphylococcus aureus

GRC Commissie RichtlijnenGevoeligheidsbeplingen (Dutch)

ICU Intensive cre unitIMP Imipenemse

KPC Klebsiella pneumoniae crbpenemse

MIC Minimum inhibitory concentrtion

MLS Mcrolide, lincosmide nd streptogrmin

MNSP Mcrolide non-susceptible S. pneumoniae

MRSA Meticillin-resistnt Staphylococcus aureus

NDM-1 New Delhi metllo-bet-lctmse

NRL Ntionl reference lbortories

NWGA Norwegin Working Group onAntimicrobils

OXA Oxcillinse gene

PBP Penicillin-binding protein

PCV Pneumococcl conjugte vccine

PNSP Penicillin-non-susceptible Streptococcuspneumoniae

PRSP Penicillin-resistnt Streptococcuspneumoniae

RNA Ribonucleic cid

SeqNet Europen Network of Lbortories forSequence Bsed Typing of MicrobilPthogens

SFM Comit de lAntibiogrmme de l SocitFrnise de Microbiologie (French)

SIR Sensitive, intermedite, resistntSHV Sulfhydryl-vrible ex tended-spectrum

bet-lctmse gene

Spa-typing S. aureus protein A-gene sequence typing

SRGA Swedish Reference Group for Antibiotics

TESSy The Europen Surveillnce System (tECDC)

TEM Temoneir extended-spectrum bet-lctmse gene

UK NEQAS United Kingdom Ntionl Externl QulityAssessment Scheme for Microbiology

VISA Vncomycin-intermedite Staphylococcus

aureus

VIM Veron integron-encodedmetllo-bet-lctmse

VRE Vncomycin-resistnt enterococci

VREF Vncomycin-resistnt Enterococcus faecalis

VRSA Vncomycin-resistnt Staphylococcusaureus

WHO World Helth Orgniztion

WHONET WHO microbiology lbortory dtbsesoftwre

Abbreviations and acronyms


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Austria

Federl Ministry of Helth

Medicl University Vienn

Elisbethinen Hospitl, Linzwww.elisbethinen.or.t

Belgium

Scientific Institute of Public Helthwww.iph.fgov.be

University of Antwerp

Bulgaria

Alexnder University Hospitl, SofiNtionl Center of Infectious nd Prsitic Diseses

Cyprus

Nicosi Generl Hospitl

Czech Republic

Ntionl Institute of Public Helth

Ntionl Reference Lbortory for Antibiotics

Denmark

Sttens Serum Institut, Dnish Study Group forAntimicrobil Resistnce Surveillnce (DANRES)www.dnmp.org

EstoniaHelth Bord

Est-Tllinn Centrl Hospitl

Trtu University Hospitl

FinlandNtionl Institute for Helth nd Welfre, FinnishHospitl Infection Progrm (SIRO)www.thl.fi/siro

Finnish Study Group for Antimicrobil Resistnce (FiRe)www.finres.fi

FrancePiti-Slptrire Hospitl

Ntionl Institute for Public Helth Surveillncewww.invs.snte.fr

French Ntionl Observtory for the Epidemiology ofBcteril Resistnce to Antimicrobils (ONERBA): A zy-Rsistnce, le-de-Frnce nd Russir networkswww.onerb.org

Ntionl Reference Centre for Pneumococci (CNRP)

Germany

Robert Koch Institute

Greece

Hellenic Psteur InstituteNtionl School of Public Helth

Ntionl nd Kpodistrin University of Athens, MediclSchoolwww.mednet.gr/whonet

Hungary

Ntionl Centre for Epidemiologywww.ntsz.hu

IrelandHelth Protection Surveillnce Centre (HPSC)www.hpsc.ie

Iceland

Ntionl University Hospitl of IcelndCentre for Helth Security nd Infectious DiseseControl

Italy

Ntionl Institute of Public Helthwww.simi.iss.it/ntibiotico_resistenz.htm

Latvia

Pul Strdins Clinicl University Hospitl

Stte Agency Infectology Centre of Ltvi

Lithuania

Ntionl Public Helth Surveillnce Lbortory

Institute of Hygiene

Luxembourg

Ntionl Helth Lbortory

Microbiology Lb, Luxembourgs Hospitl Centre

MaltaHospitl of Mlt

Netherlands

Ntionl Institute for Public Helth nd the Environment

Norway

University Hospitl of North Norwy

Norwegin Institute of Public HelthSt. Olv University Hospitl, Trondheim

Poland

Ntionl Medicines Institute

Portugal

Ntionl Institute of Helth Dr. Ricrdo Jorgewww.insrj.pt

Ministry of Helth

Directorte-Generl of Helth

Romania

Ntionl Institute of Reserch nd Development forMicrobiology nd Immunology Cntcuzino

Institute of Public Helth

National institutions/organisationsparticipating in EARS-Net


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Slovenia

Ntionl Institute of Public Helth

University of Ljubljn

Spain

Helth Institute Crlos lllwww.isciii.es/htdocs/en/index.jsp

Ntionl Centre of Epidemiology

Sweden

Swedish Institute for Infectious Disese Controlwww.smittskyddsinstitutet.se

United KingdomHelth Protection Agencywww.hp.org.uk

Helth Protection Scotlnd

Public Helth Agency Northern Irelnd


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This is the first Annul Report of the EuropenAntimicrobil Resistnce Surveillnce Network (EARS-Net) fter the trnsition of the Europen AntimicrobilResistnce Surveillnce System (EARSS) to the EuropenCentre of Disese Prevention nd Control (ECDC) by Jnury . This report represents the continution ofthe series of highly vlued EARSS Annul Reports pub-lished by the network since .

During the lst decde, ntimicrobil resistnce hsmoved stedily to more nd more prominent positionon the public helth gend in Europe. The surveillnceof ntimicrobil resistnce conducted previously by

EARSS, nd currently by EA RS-Net, hs plyed n impor-tnt role to provide documenttion of the occurrencend spred of ntimicrobil resistnce, nd to incresewreness of the problem t the politicl level, mongpublic helth officils nd in the scientific community.

Bsed on the ntimicrobil resistnce dt reported toEARS-Net by 8 countries in 9, nd on the resultsof trend nlyses including EARSS dt from previousyers, the resistnce sitution in Europe displys lrgevrition depending on pthogen type, ntimicrobilsubstnce nd geogrphic region.

In 9, the most concerning resistnce results come

from the rpidly decresing susceptibility of invsiveEscherichia coli to bsiclly ll ntimicrobil gentsincluded in the EARS-Net surveillnce except crbp-enems, nd from the high prevlence of resistncein Klebsiella pneumoniae to third-genertion ceph-losporins, fluoroquinolone nd minoglycosides. In hlfof the reporting countries, the proportion of multire-sistnt K. pneumoniae isoltes (combined resistnce tothird-genertion cephlosporins, fluoroquinolones ndminoglycosides) is bove %, nd few countriesre now lso reporting high proportions of resistnceto crbpenems. These ntibiotics hve been widelyused in mny countries due to the incresing rte of

extended-spectrum bet-lctmse (ESBL) producingEnterobctericee with consequent impct on theemergence of crbpenemse production (VIM, K PC ndNDM-), especilly in K. pneumoniae.

The highest resistnce proportions in E. coli werereported for minopenicillins rnging up to 66%.Irrespective of the high level of resistnce, proportionscontinue to increse even in countries lredy pre-senting resistnce levels well bove %. Resistnceto third-genertion cephlosporins in E. coli hs lsoincresed significntly during the lst four yers in morethn hlf of the reporting countries. This resistnce isdirectly linked to the high proportions (8%) of

ESBL positives mong the resistnt isoltes in countriesreporting on ESBL in 9.

Other trends in the occurrence of resistnce reported toEARS-Net bring hope tht ntionl efforts on infectioncontrol nd efforts trgeted t continment of resistncemy in some cses bring the development of resistnceto hlt, or even reverse undesirble resistnce trends,s exemplified by the development for meticillin-resist-nt Staphylococcus aureus (MRSA). Even though theproportion of MRSA mong Staphylococcus aureus is stillbove % in out of 8 countries, the occurrence ofMRSA is stbilising or decresing in some countries nd sustined decrese ws observed in Austri, Frnce,Irelnd, Ltvi nd UK.

Furthermore, the United Kingdom hs shown consist-ent reduction of resistnt proportions in K. pneumoniaefor ll the ntibiotic clsses under surveillnce, ndin few countries (Greece, Germny, Itly nd Frnce)the efforts to control glycopeptide resistnce inEnterococcus faecium seem to be successful nd result-ing in continuous decrese of proportions of resistntisoltes. Menwhile, high-level minoglycoside resist-nce in Enterococcus faecalis seems to stbilise t reltively high level. The mjority of countries reportedproportions of resistnt isoltes between 3% nd %.

For Streptococcus pneumoniae, non-susceptibility topenicillin is generlly stble in Europe nd non-suscep-tibility to mcrolides hs declined in six countries whileno country reported incresing trends. For Pseudomonasaeruginosa, high proportions of resistnce to fluoroqui-nolones, crbpenems nd combined resistnce hvebeen reported by mny countries, especilly in southernnd estern Europe.

For severl ntimicrobil nd pthogen combintions,e.g. fluoroquinolone resistnce in E. coli, K. pneumoniae,P. aeruginosa nd for MRSA, north to south grdient isevident in Europe. In generl, lower resistnce propor-tions re reported in the north nd higher proportionsin the south of Europe likely reflecting differences in

infection control prctices, presence or bsence of legis-ltion regrding prescription of ntimicrobils nd otherfctors known to influence the occurrence of resist-nce. However, for K. pneumoniae, incresing trends ofresistnce to specific ntibiotic clsses nd of multire-sistnce hve been observed lso in northern Europencountries, like Denmrk nd Norwy, with trditionllyprudent pproch to the ntibiotic use.

In ddition to the regulr trend nlysis nd situtionoverview, this 9 EARS-Net report fetures newfocus chpter providing in-depth nlysis for E. colindMRSA. These nlyses re bsed exclusively on dtfrom lbortories reporting consistently over severl

yers. The in-depth nlysis confirms consistent risein multidrug resistnce nd revels stedy nd sig-nificnt decline of ntimicrobil susceptibility in E. coli

Summary


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over severl yers. For MRSA, the observed declinelikely reflects the efficcy of infection control mesurest hospitl level, nd my even leve some hope for thesuccess of continment strtegies in other res.

In conclusion, the dt reported to EARS-Net for 9by the prticipting countries provide knowledgebseline on the occurrence of ntimicrobil resistncein Europe nd document the unfortunte nd stedilydiminishing ntimicrobil tretment options for mjorbcteril pthogens.


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The results presented in this focus chpter re bsedon dt from lbortories (n=98) tht prticipted toEARS-Net nd previously EARSS from to 9,nd reported continuously during the period on suscep-tibility of Escherichia coli nd Staphylococcus aureusto selected ntimicrobil gents. The long-stndingcontribution of these lbortories to the surveillnce

of ntimicrobil resistnce llow for ccurte compri-son of proportions of resistnt isoltes nd number ofreported infections over time. Thus, results presented inthis focus chpter my be slightly different from resultsobtined from the full group of lbortories reporting toEARS-Net nd previously to EARSS.

Key points A significnt decline of ntimicrobil susceptibil-

ity ws observed for E. coli between nd9, with concomitnt increse of reportedbloodstrem infections of 7%.

S. aureus showed different tendency, with significnt decrese of the proportion of meticil-lin resistnce (MRSA) nd n increse of 34% inthe number of reported bloodstrem infections.

The trends observed for E. colicould suggest nincrementl burden of disese cused by thismicroorgnism, nd the simultneous decline ofntimicrobil susceptibility is serious publichelth concern.

The reduction of the MRSA proportion nd thereltive continment of the number of S. aureusinfections could result from efficcy of infec-

tion control mesures t hospitl level in somecountries. However, efforts to reduce MRSAoccurrence should remin priority, irrespectiveof decresing trends.

Escherichia colind Staphylococcus aureus re the mostfrequent cuses of bloodstrem infections (BSI). Thetemporl trends of resistnce nd the trends in the inci-dence of BSI cused by these microorgnisms, observedthrough the EARSS/EARS-Net dt, re described for theperiod 9.

The ntimicrobil susceptibility of E. coli BSI isoltesshows n lrming Europe-wide decline s previouslyreported by EARSS []. Incresing resistnce in E. coli

nd combined resistnce of invsive nd non-invsiveisoltes is reported in severl ntionl Europen surveil-lnce reports [6]. At the sme time, the proportionof MRSA hs showed significnt decrese in mnyEuropen countries. The numbers of BSI cused byMRSA, s reported by the mndtory surveillnce sys-tem in Englnd, decresed by 6% between 4 nd

8 [7], nd in Frnce significnt decrese in theoccurrence of MRSA ws reported in 8 [8] A similrreduction of the rte of helthcre-ssocited invsiveMRSA infections hs been observed t popultion levelin the United Sttes [9].

A totl of 98 lbortories in countries reported con-tinuously from to 9. The number of lbortoriesper country rnged between (Icelnd nd Mlt) nd33 (Czech Republic) (Tble .). Considering the wholegroup of selected lbortories, the reported numberof E. coli BSI, incresed by 7% from 688 in to 8 4 in 9. In the sme period, S. aureus BSIshowed 34% increse from 7 8 to 3 (Figure .);

this increse ws observed in most but not ll countries(Tble .).

During this intervl, the proportion of third-genertioncephlosporin-resistnt E. coli incresed significntlyfrom .7% to 8% (p < .) nd the proportion of MRSAdecresed from .% to 9.7% (p < .) (Figure .).The trends of resistnce proportions t country levelwere consistent with those of the whole group of 98lbortories in 8 countries out of for E. coli nd inseven countries out of for S. aureus.

Combined resistnce in E. coli (defined s resistnceto two, three nd four ntibiotic clsses reported toEARS-Net) showed significnt increse (Figure .3)(p < .) nd becme frequent phenotype in mostcountries, whereby single resistnce diminished from37.% in nd 3.8% in 9 (p < .). The pro-portion of isoltes susceptible to ll four ntibioticclsses decresed from .4% in to 4.7% in 9(p < .).

The decline of ntimicrobil ctivity in E. coli ws evi-dent both through the observed increse of combinedresistnce nd through the reduction of full suscepti-bility to the ntimicrobils included in the nlysis. Inthe sme time period nd considering the sme dt

source, significnt decrese of meticillin resistncews observed for S. aureus. For this species, the numberof BSI incresed less (+34%) thn for E. coliBSI (+7%).

2 Escherichia coliandStaphylococcusaureus: bad news and good news.

Analysis of data from laboratories reportingcontinuously from 2002 to 2009


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Importntly, most of the rise (38% of 7%) in E. coliBSIppered to be due to isoltes resistnt to two or morentibiotics. Furthermore, the increse in the numberof BSI ws similr for meticillin-susceptible S. aureus(MSSA, 37%) nd for fully susceptible E. coli(39%).

Despite the possible limittions of the presented results(see section .), the trends of third-genertion ceph-losporins nd combined resistnce re relevnt findingstht deserve further considertion. According to theresults, it ppers tht, during the study period, theemergence nd spred of combined resistnce is themin fctor tht influences the decline of ntimicrobilctivity ginst E. coli. In the period 9, only nincrese of combined resistnce with concurrent rel-tive reduction of the proportion of single resistnce wsobserved. The resistnt subpopultion with the lrgestreltive growth in the period 9 ws the resist-nce to ll the four ntibiotic clsses under surveillnce:

this pttern incresed more thn fivefold from .6% to3.4%. This trend suggests tht inside the subpopul-tion of resistnt isoltes there ws continuous reltivegrowth of combined resistnce possibly cused by theddition of resistnce trits to strins tht were lredyresistnt to t lest one mong the considered ntibioticclsses. This trend my be explined by the spred ofmultidrug-resistnt plsmids, which lso contin genesfor extended-spectrum bet-lctmse (ESBL) produc-tion [].

The growing number of E. coliBSI indictes n incres-ing burden of disese cused by this microorgnism. A

similr trend in the number of reported cses of E. coliBSI hs been observed in Englnd, Wles nd NorthernIrelnd by the ntionl voluntry surveillnce scheme, inthe period 48. The increse (38%) observed by

the British surveillnce system is greter thn the 6%increse in ll BSI reported in the country during thesme time period [].

In conclusion, the reported dt show significnt

increse of ntimicrobil resistnce in E. coli invsiveisoltes nd n overll increse in BSI cused by thismicroorgnism. This is serious public helth concernsince, if the incresing trend of ntimicrobil resist-nce nd the spred of ESBL re not contined, the useof crbpenems will increse fvouring the emergenceof crbpenemse-producing enterobcteri. This hsbeen lredy observed for Klebsiella pneumoniae inGreece, Isrel nd Cyprus [].

At the sme time, S. aureus showed reltively smllerincrese in the number of reported BSI, but significntdecrese in the proportion of MRSA overll in EARSS/EARS-Net. This could be the result of the public helth

efforts trgeted t continment of MRSA in severlEuropen countries nd in the US. Even though n over-ll decresing trend for MRSA is evident in Europe, notll countries contribute to this result. Efforts to reduceMRSA occurrence should remin priority irrespectiveof decresing trends.

In this perspective, coordinted interntionl surveil-lnce is prticulrly importnt in order to obtin ccurteknowledge of the occurrence nd spred of ntimicrobilresistnce nd to enble plnning of public helth inter-ventions imed t prevention nd control of the problem.

2.1 Methods of analysis Dt for E. coli nd S. aureus BSIs were extrctedfrom the EARSS/EARS-Net dtbse for lbortories

Table 2.1: Average numbers ofEscherichia coliandStaphylococcus aureus isolates per country reported yearly from2002 to 2009 by laboratories participating continuously in EARSS/EARS-Net during this time interval

Country Number of laboratoriesNumber ofE. coliisolates average per year

()Number ofS. aureus isolates average per year

()

Austria 10 802 630

Belgium 9 646 343

Bulgaria 7 96 82

Czech Republic 33 1 837 1 290Estonia 5 142 125

Finland 5 849 381

France 12 1 583 1 018

Germany 2 156 121

Greece 22 829 472

Hungary 14 446 526

Iceland 1 97 56

Ireland 15 1 086 961

Italy 3 237 166

Luxemburg 4 176 80

Malta 1 104 96

Netherlands 4 291 238

Norway 7 975 467

Portugal 8 559 574

Slovenia 9 572 321

Spain 19 1 973 835

Sweden 3 578 331

United Kingdom 5 641 373


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Figure 2.1: Yearly number of bloodstream infections caused by Escherichia coliandStaphylococcus aureus. EARSS/EARS-Net 20022009 (22 countries/198 laboratories)

Figure 2.2: Proportion of third-generation cephalosporin-resistant Escherichia coli(CREC) and meticillin-resistantStaphylococcu s aureus (MRSA). EARSS/EARS-Net 20022009 (22 countries/198 laboratories)

Figure 2.3: Combined resistance (R) ofEscherichia colito aminopenicillins, third-generation cephalosporins,fluoroquinolones and aminoglycosides. EARSS/EARS-Net 20022009 (22 countries/198 laboratories)

E. coli

S. aureus

No.

bloodstreami

nfections

987643

Third-genertion cephlosporin-resistntE. coli

MRSA

Percentresista

ntisolatesamongspecies

987643

R to two ntimicrobil clsses

R to three ntimicrobil clsses

R to four ntimicrobil clsses

Percentisolates

4

6

8

987643

Only lbortories reporting susceptibility results for specific ntimicrobils continuously during the period 9 re included in the nlysis.




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reporting susceptibility results continuously dur-ing the period 9 for minopenicillin,fluoroquinolones, third-genertion cephlosporinnd minoglycosides in E. coli nd for oxcillin inS. aureus. Countries with no lbortory prticipting

for the entire period or with smll mount of dt (lessthn isoltes per microorgnism nd per yer) werenot included in the nlysis. Only the first isolte perptient, microorgnism nd yer ws included.

The number of BSI cused by E. colind S. aureus ndthe proportions of third-genertion cephlosporinresistnt E. colind of MRSA were clculted for echyer of the period 9. Three dditionl nti-biotic clsses (minopenicillins, minoglycosides ndfluoroquinolones) were lso considered for E. coli tossess the ptterns of combined resistnce of thispthogen.

The significnce of the temporl trends for resistnceproportions ws evluted by the Cochrn-Armitgetest for trend.

2.2 Limitations of the analysis Even considering stble group of lbortories, it is

still possible tht chnge in the popultion covergeof these lbortories hs occurred over time.

The different trends observed for E. colind S. aureuscould lso be explined by scertinment bis ledingto higher reporting ofE. coliinfections nd cused byn increse of empiricl tretment filures triggeringdelyed dignostic procedures (blood culture).

The indictor used to monitor the resistnce trendws the SIR (sensitive, intermedite, resistnt) inter-prettion, since the ctul MIC (minimum inhibitoryconcentrtion) vlues re not systemticlly mdevilble by prticipting lbortories. ReportingMIC insted of the SIR interprettion defined byclinicl brekpoints would improve the monitor-ing of dynmic nd subtle chnges of ntimicrobilsusceptibility.

2.3 References

. RIVM. EARSS nnul report 8. Bilthoven: Rksinstituut voor

Volksgezondheid en Milieu; 9.. DANMAP 8. Jensen VJ, Hmmerum A (eds). Consumption of nti-

microbil gents nd occurrence of ntimicrobil resistnce in bc-teri from food nimls, food nd humns in Denmrk. Copenhgen:Ntionl Food Institute, Technicl University of Denmrk; 9.

3. Helth Protection Agency. Antimicrobil Resistnce nd Prescribingin Englnd, Wles nd Northern Irelnd, 8. London: HelthProtection Agency; 8.

4. NORM/NORM-VET 9. Norstrm M, Simonsen GS (eds). Usge ofAntimicrobil Agents nd Occurrence of Antimicrobil Resistnce inNorwy. Troms/Oslo; .

. RIVM, SWAB. NethMp 9. Consumption of ntimicrobil gentsnd ntimicrobil resistnce mong mediclly importnt bcteri inthe Netherlnds.

6. SWEDRES 9. Dohnhmmr U, Olsson-Liljequist B (eds). AReport on Swedish Antimicrobil Utilistion nd Resistnce inHumn Medicine. Swedish Strtegic Progrmme ginst AntibioticResistnce (STRAMA). Stockholm: Swedish Institute for InfectiousDisese Control; .

7. Person A, Chronis A, Murry M. Voluntry nd mndtory surveil-lnce for methicillin-resistnt Stphylococcus ureus (MRSA) ndmethicillin-susceptible S. ureus (MSSA) bcteremi in Englnd. JAntimicrob Chemother. 9;64(Suppl ):i-7.

8. Anonymous. Recent trends in ntimicrobil resistnce mongStreptococcus pneumonie nd Stphylococcus ureus isoltes:the French experience. Euro Surveill. 3 Nov 8;3(46).

9. Kllen AJ, Mu Y, Bulens S et l. Helth cre-ssocited invsiveMRSA infections, 8. JAMA ;34(6):64-648.

. Coque TM, Bquero F, Cnton R. Incresing prevlence of ESBL-producing Enterobctericee in Europe. Euro Surveill Nov

8;3(47).. HPA. Escherichi coli bcteremi in Englnd, Wles, nd Northern

Irelnd, 4 to 8. London: Helth Protection Agency, 9.


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3.1. IntroductionSince , EARSS hs been orgnising externl qulityssessment (EQA) exercises of ntimicrobil suscepti-bility testing in collbortion with UK NEQAS (UnitedKingdom Ntionl Externl Qulity Assessment Service).UK NEQAS is bsed t the Helth Protection Agency, inLondon, nd is non-profit orgnistion with more thn3 yers experience with externl qulity ssessment indifferent countries (www.ukneqsmicro.org.uk).

The rtionle of these EQA exercises is:

to ssess the bility of prticipting lbortories toidentify ntimicrobil resistnce of clinicl nd publichelth importnce;

to determine the ccurcy of susceptibility test resultsreported by individul lbortories; nd

to decide on the overll comprbility of routinely col-lected test results between lbortories nd countriesnd thus provide the mens for justifying the poolingnd comprison of ntimicrobil susceptibility test(AST) dt cross Europe.

The externl qulity ssessment exercise, held in thesecond hlf of 9, ws open to ll countries prtici-

pting in EARSS in 9, including Bosni-Herzegovin,Croti, Isrel nd Turkey. A pnel of six strins wsincluded in the exercise. The strins were chrcterisednd tested in two reference lbortories (AddenbrookesHospitl, Cmbridge, nd City Hospitl, Birminghm).Both reference lbortories confirmed MICs ndinterpreted the results ccording to frequently usedbrekpoint criteri such s CLSI nd EUCAST, s indi-cted in ech of the species chpters.

3.2. ResultsStrin pnels were distributed to 886 prticiptinglbortories, who were sked to report the clinicl sus-ceptibility ctegoristion susceptible, intermeditend resistnt (S, I, R) ccording to the guideline used.The lbortories returned 77 (87%) reports, which isequivlent to the return rte of previous yers. Turkeyws not ble to perform the tests, due to difficultiesrelted to the shipment of strins. Figure 3. showsthe proportion of prticipting lbortories returningreports per country.

All results were collected vi the UK NEQAS internetwebsite. Results were nlysed nd considered con-cordnt if the reported ctegoristion greed with theinterprettion of the reference lbortories.

For the determintion of AST results, lbortories usedutomted methods (3%), disc diffusion tests (33%),

or combined methods (3%). For species identific-tion, 6% used utomted nd 4% used conventionlmethods.

The mjority of lbortories pplied CLSI guidelines(68%), nd some countries used ntionl guidelines,e.g. Frnce (SFM), UK (BSAC), nd Sweden (SRGA). Theuse of EUCAST guidelines ws minly reported by lbo-rtories tht utilise utomted dignostic test systemslredy clibrted for EUCAST brekpoints. However,the UK, Sweden, the Netherlnds, Germny, Frnce ndNorwy hve been implementing EUCAST brekpointsin their ntionl MIC brekpoint recommendtions s

hrmonised brekpoints hve been greed, nd inddition hve djusted the interprettion of their diskdiffusion methods ccordingly. Hrmonistion effortsbetween the different ntionl guideline committeeshve ccomplished stisfctory degree of greementnd, therefore, previous discrepncies between differ-ent guidelines hve become less significnt. Figure 3.shows the dherence to (inter)ntionl guidelines bynumber of lbortories per country.

3.2.1. Specimen 9448 Escherichia coli

This specimen consisted of n Escherichia coli withCTX-M-4 ESBL production. Unlike most TEM- nd SHV-

derived ESBLs, CTX-M enzymes re more ctive ginstcefotxime thn ceftzidime. This orgnism shouldclerly be interpreted s resistnt to cefotxime (MIC 8 mg/L) using EUCAST (S , R > mg/L), nd CLSI(S 8, R 64 mg/L) guidelines. With ceftzidime (MIC mg/L) the isolte ppers intermedite by EUCASTguidelines (S , I 8, R > 8 mg/L) nd susceptibleby stndrd CLSI guidelines (S 8, I 6, R 3 mg/L).However, current EUCAST expert rules recommend thtESBL-producing isoltes re reported resistnt if theypper intermedite in routine tests nd intermedi-te if they pper susceptible. Resistnce should bereported if CLSI ESBL screening methods re used s

recommended.Detection of reduced susceptibility to cefotxime ndceftrixone ws not problem nd < % prticipntsreported the orgnism susceptible to these gents. Withceftzidime, reports of intermedite (%) nd suscep-tible (6%) were more common. A lrge mjority (98%)of prticipnts testing for ESBLs correctly reported theorgnism ESBL-positive.

This orgnism ws susceptible to pipercillin+tzobctmin MIC tests (MIC 4 mg/L). Despite some reports ofclinicl efficcy, there hs been considerble debtebout whether ESBL-producing strins from seri-

ous infections should be reported susceptible tobet-lctmse inhibitor combintions when theypper susceptible in routine tests. While the mjority

3 External Quality Assessment Exercise(EQA) 2009


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Figure 3.1: Proportion of participating laboratories returning reports per country, 2009

Figure 3.2: Adherence to guidelines*: number of laboratories per country

4 6 8

UKTRSISEROPTPL

NONL

MTLVLULTITISILIE

HUHRFRFI

ESELEEDKDECZCY

BGBEBAAT

No results

Results

Countrycode

Number of lbortories

3 4 6 7 8

UKSISEROPTPL

NONLMTLVLULTITISIL

IEHUHRFRFI

ESELEEDKDECZCYBUBEBAAT

COMB

CRG

DIN

EUCAST

FIRE

NCCLS

NWGA

SFM

SRGA

Other

BSAC

Coun

trycode


BSAC, British Society for Antimicrobil Chemotherpy; CRG, (Dutch) Commissie Richtlijnen Gevoeligheidsbeplingen; DIN, Deutsche Industrie Norm; EUCAST,Europen Committee on Antimicrobil Susceptibility Testing; NCCLS/CLSI, (Americn) Clinicl nd Lbortor y Stndrds Institute; NWGA, Norwegin Working Groupon Antimicrobils; SFM, Comit de lAntibiogrmme de l Socit Frnise de Microbiologie; SRGA, Swedish Reference Group for Antibiotics.BSAC, CRG, DIN, NWGA, SFM nd SRGA hve implemented EUCAST brekpoints for MIC determintions nd hve djusted the interprettion of their disk dif fusionsccordingly.The externl qulity ssessment exercise ws open to ll countries prticipting in EARSS in 9.BA = Bosni-Herzegovin; HR = Croti; IL = Isrel.

The externl qulity ssessment exercise ws open to ll countries prticipting in EARSS in 9.BA = Bosni-Herzegovin; HR = Croti; IL = Isrel; TR = Turkey.


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of prticipnts (7%) reported the orgnism suscepti-ble to pipercillin+tzobctm, significnt proportionsreported intermedite (9%) or resistnt (%).

In reference tests, this orgnism ws resistnt to gen-

tmicin, highly vrible in susceptibility to tobrmycin(reference MICs 4 to > 8 mg/L) nd susceptible tomikcin. It is likely tht this reflects production of nANT () enzyme, expression of which cn be vrible.EUCAST expert rules suggest tht such isoltes shouldbe reported resistnt to tobrmycin if they pper inter-medite. While 99% prticipnts reported the orgnismgentmicin resistnt nd 98% mikcin susceptible,for tobrmycin, 3%, 8% nd 4% were reportingresistnt, intermedite nd susceptible, respectively(Tble 3.).

3.2.2. Specimen 9449 Klebsiella pneumoniae

This orgnism is Klebsiella pneumoniae with high-level bet-lctmse production; not only penicillinresistnt, but lso reduced susceptibility to bet-lct-mse inhibitor combintions. Pipercillin+tzobctmMICs of 64 to 8 mg/L for this orgnism indicte resist-nce by EUCAST brekpoints nd intermedite/resistntby CLSI brekpoints. Among prticipnts, 7% reportedthe orgnism resistnt, % intermedite nd % sus-ceptible. ESBL production ws incorrectly reported by9% prticipnts nd this ws frequently ssocited withincorrect reporting of resistnce to cefotxime, ceftrix-one nd ceftzidime by these prticipnts (Tble 3.).

3.2.3. Specimen 9450Streptococcus

pneumoniae

This orgnism is Streptococcus pneumoniae withreduced susceptibility to penicillin (MIC . mg/L).For S. pneumoniae with no mechnism of resistnce topenicillin, MICs re .6 mg/L. EUCAST guidelinesdivide reduced susceptibility to penicillin into interme-dite (penicillin MIC . mg/L) nd resistnt (MIC> mg/L) ctegories. However, the interprettion of sus-ceptibility to penicillin depends on whether the isolte isfrom ptient with meningitis or other infections (mostcommonly pneumoni). Strins with intermedite sus-ceptibility re tretble with the high doses of penicillin,mpicillin or moxicillin routinely used to tret pneumo-

ni. Hence such strins my be reported susceptible inthis sitution. Ptients with meningitis cused by strinswith intermedite susceptibility to penicillin re unlikelyto respond to therpy, nd hence such strins should bereported s resistnt in this sitution.

Overll, 9% prticipnts reported resistnce in theoxcillin screening test for penicillin resistnce. A fur-ther 3% reported the isolte intermedite to oxcillin,lthough the oxcillin screening test does not distin-guish penicillin intermedite nd resistnt isoltes ndpublished guidelines do not include n intermeditectegory.

The prticipnts results for penicillin will include thosetht only screened for reduced susceptibility with

oxcillin discs, those tht screened with oxcillin ndconfirmed with penicillin MIC, nd those tht testedwith other methods. Overll, 76% reported the isolte sbeing of intermedite susceptibility to penicillin, with further 8% reporting the isolte resistnt. Susceptibility

reported to clinicins for this orgnism if isolted fromcses of meningitis or pneumoni indictes tht mnyprticipnts do interpret test results to suit the cliniclsitution. Eighty-five per cent reported the isolte sresistnt when the isolte ws from cse of meningitisnd 7% s susceptible when the isolte ws from cseof pneumoni, but significnt numbers of prticipntsinterpreted the orgnism s intermedite in susceptibil-ity to penicillin irrespective of whether the isolte wsfrom meningitis (% reported intermedite) or frompneumoni (6% reported intermedite). However, it isrecognised tht some locl reporting guidelines myrecommend ctegoristion of pneumoni isoltes withintermedite penicillin susceptibility s intermedite,with the note tht the isolte is susceptible if the ptientis treted with high dose.

With EUCAST, brekpoints for ciprofloxcin wild typeorgnisms such s this (MIC mg/L) re reported inter-medite in susceptibility to ciprofloxcin, reflecting theuncertin outcome of therpy. CLSI do not give cipro-floxcin brekpoints for S. pneumoniae. This uncertintyws reflected in the high discrepncy rte in reportingfor this gent (69% susceptible, 7% intermedite nd4% resistnt) (Tble 3.3).

3.2.4. Specimen 9451 Pseudomonas aeruginosa

This orgnism is Pseudomonas aeruginosa withborderline resistnce to pipercillin+tzobctm(MIC 364 mg/L) but susceptible to ceftzidime, susceptibility profile seen with some bet-lctmse-producing strins. This orgnism produces the PSE-4(CARB-) bet-lctmse. The borderline resistnce topipercillin+tzobctm ws reflected in the vritionin susceptibility reported by prticipnts, with 49%reporting susceptible, % intermedite nd 39% resist-nt. The different ctegoristion lrgely reltes to thebrekpoint differences between EUCAST (susceptible 6 mg/L, resistnt > 6 mg/L) nd CLSI (susceptible 64 mg/L, resistnt 8 mg/L) (Tble 3.4).

3.2.5. Specimen 9452 Pseudomonas aeruginosa

This orgnism is Pseudomonas aeruginosa resistntto gentmicin nd susceptible to other reference gentstested. Some lbortories experienced problems withpipercillin+tzobctm testing in tht overll 4%prticipnts reported the isolte intermedite nd %resistnt. The reson for the problems is not obviouss the isolte ws clerly susceptible in reference tests(Tble 3.).

3.2.6. Specimen 9453Staphylococcus aureus

This orgnism is meticillin-resistnt Staphylococcus

aureus (EMRSA-6) nd most prticipnts correctlyreported resistnce. There ws no significnt difference


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Table 3.1:Escherichia coli(9448): Minimum inhibitory concentration (MIC) and intended results reported by referencelaboratories and the overall concordance of the participating laboratories

Antibiotic agentMIC range ref. lab. Intended interpretation

from to EUCAST/CLSI Overall concordance (%)

Amikacin 1 1 S 98

Amoxicillin NT* - R 93

Ampicillin > 128 > 128 R 100

Cefotaxime 128 > 128 R 97

Ceftazidime 2 2 R expert rule 80

Ceftriaxone > 128 > 128 R 99

Ciprofloxacin 64 128 R 100

ESBL positive 98

Gentamicin 32 64 R 99

Imipenem 0.12 0.12 S 100

Meropenem 0.03 0.03 S 99

Piperacillin 128 128 R 99

Piperacillin+tazobactam 2 4 S 71

Tobramycin 4 > 128 IR/SIR

* Not tested, result inferred from mpicillin.

Table 3.2:Klebsiella pneumoniae (9449): Minimal inhibitory concentration (MIC) and intended results reported by thereference laboratories and the overall concordance of the participating laboratories



Amikacin 64 64 R 97

Ampicillin/amoxicillin 128 128 R 100

Cefotaxime 0.12 0.5 S 92

Ceftazidime 0.12 0.25 S 93

Ceftriaxone 0.5 0.5 S 93

Ciprofloxacin 0.015 0.03 S 100

ESBL - - negative 91


Imipenem 0.12 0.12 S 99Meropenem 0.03 0.03 S 99

Piperacillin 64 128 I/R 99

Piperacillin+tazobactam 64 128 I/R 95

Tobramycin 16 128 R 99

Table 3.3:Streptococcus pneumoniae (9450): Minimum inhibitory concentration (MIC) and intended results reported bythe reference laboratories and the overall concordance of the participating laboratories



Cefotaxime 0.06 0.12 S 98Meningitis - - S 96

Pneumonia - - S 99

Ceftriaxone 0.06 0.12 S 98

Meningitis - - S 95

Pneumonia - - S 98

Ciprofloxacin 1 1 I/ 27

Clindamycin 0.12 0.12 S 99

Erythromycin 0.12 0.25 S 99

Oxacillin - - R 92

Penicillin 0.25 0.25 I 76

Meningitis - - R 85

Pneumonia - - S 70


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Table 3.6:Staphylococcus aureus (9453): Minimum inhibitory concentration (MIC) and intended results reported by thereference laboratories and the overall concordance of the participating laboratories



Cefoxitin 8 16 R 95Ciprofloxacin 0.5 0.5 S 95

Erythromycin 4 128 I/R 93

Fucidic acid 0.06 0.12 S 100

Gentamicin 0.25 0.50 S 99

Methicillin NT* R 97

Oxacillin 8 32 R 94

Penicillin 1 4 R 99

Rifampicin 0.004 0.008 S 99

Teicoplanin 1 1 S 99

Tetracycline 64 64 R 97

Vancomycin 1 2 S 99

* Not tested, result inferred from oxcillin nd cefoxitin.

Table 3.4:Pseudomonas aeruginosa (9451): Minimum inhibitory concentration (MIC) and intended results reported bythe reference laboratories and the overall concordance of the participating laboratories



Amikacin 1 8 S 100

Ceftazidime 1 2 S 98


Gentamicin 1 4 S 97

Imipenem 1 2 S 99

Meropenem 0.5 2 S 99

Piperacillin+tazobactam 32 64 R/S 39

Tobramycin 0.5 1 S 99

Table 3.5:Pseudomonas aeruginosa (9452): Minimum inhibitory concentration (MIC) and intended results reported bythe reference laboratories and the overall concordance of the participating laboratories



Amikacin 1 4 S 99

Ceftazidime 1 2 S 99



Imipenem 1 2 S 99

Meropenem 0.5 2 S 99

Piperacillin+tazobactam 4 8 S 84

Tobramycin 0.5 1 S 99


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in relibility of detection of meticillin resistnce in testswith oxcillin (94% prticipnts reported resistnce)nd cefoxitin (9% prticipnts reported resistnce).

About third of prticipnts reported result for meti-

cillin (97% resistnt) but it my be tht oxcillin orcefoxitin were ctully tested. Erythromycin referenceMICs were very vrible (4 to > 8 mg/L), probblybecuse resistnt colonies of this orgnism grew slowly.MICs in this rnge indicte resistnce by EUCAST brek-points nd intermedite/resistnt by CLSI brekpoints;93% prticipnts reported the orgnism resistnt ndonly 6% intermedite (Tble 3.6).

3.3 ConclusionsIn this eighth EARSS EQA exercise, prticiption oflbortories ws high. The results show tht rou-tinely reported results, s collected by EARSS in most

instnces, hve sufficient ccurcy to provide goodestimtes of overll resistnce prevlence nd trends.The overll concordnce ws high, except in cse of bor-derline susceptibility, when vrious guidelines revelremining discrepncies in routine susceptibility testing,nd when brekpoint ws recently chnged. The ltterws found for penicillin susceptibility of Streptococcuspneumoniae in reltion to the source of the isolte, wherethe isolte ws regulrly reported non-susceptible forpneumoni. Furthermore, differences in interprettionof results were found for pipercillin+tzobctm (sfrequently noted previously).

EARSS Mngement Tem would like to thnk UK NEQASfor Microbiology, the reference lbortories, the mem-bers of the Advisory Bord, the country coordintors forthe swift distribution of the strins, nd ll the prtici-pting lbortories for their excellent response rte.


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4.1 IntroductionFor correct interprettion of the EARS-Net dt on nti-microbil resistnce, ccurte bckground informtionis importnt. Therefore, lbortory nd hospitl nddenomintor dt re collected nd presented in thischpter.

4.2 MethodsQuestionnires, in Microsoft E xcel files, were sent to theEARS-Net contct points t the beginning of June .The contct points distributed the questionnires to theprticipting lbortories nd hospitls in their country.Informtion ws collected on the totl number of bloodculture sets processed in the lbortories, nd thenumber of hospitl beds for ech prticipting hospitl,the type of hospitl, the bed occupncy nd the numberof dmissions. The ntionl dt mngers received thecompleted questionnires, compiled them nd producedthe finl formt suitble for uploding in the EuropenSurveillnce System (TESSy). Lbortories hve beendefined s reporting denomintor dt if they hve pro-vided the number of blood culture sets performed forone or for more thn one hospitl; hospitls hve beendefined s reporting denomintor dt if they hve pro-

vided the number of beds.

4.3 ParticipationFifteen out of 8 countries reporting ntimicrobilresistnce results returned hospitl denomintor dtwhile 4 countries returned lbortory denomintordt. Considering the responding countries, 9 of the37 lbortories (7.3%) nd 66 of the 87 hospitls(69.6%) reporting ntimicrobil susceptibility resultsfor the countries in 9, lso provided denomintordt (Figures 4.4., Tbles 4.4.3). Some denomin-tor dt of lbortories nd hospitls not prticiptingto ntimicrobil resistnce surveillnce, or reporting

zero cses, hve been included in Figure 4., but werenot included in the nlysis.

4.4 Population coverageThe popultion coverge of ntimicrobil resistncedt t country level is not reported for 9 becuseof the low number of countries submitting denomintordt nd becuse of possible limittions in the use ofthe dt on popultion coverge:

lbortories/hospitls reporting ntimicrobil sus-ceptibility dt do not lwys provide denomintordt nd this could give bised figure of the country

popultion coverge since it cn be clculted only forlbortories/hospitls with denomintor dt; nd

lbortories nd hospitls cluster in big cities nd,for this reson, some of the ctchment res overlp.This could led to double counts, which could rtifi-cilly increse the estimted coverge.

The coverge t Europen level possibly incresed in9 compred to the previous yer since the number ofreporting lbortories incresed from 8 in 8 to 96in 9. A high coverge t country level is very impor-tnt to properly describe the country profile nd it lsollows more ccurte clcultion of the culture rtend the MRSA incidence rte. Clcultion of the MRSAincidence rte (not included in the 9 report) would

be bsed on the ssumption tht ech hospitl is servedby one lbortory. Therefore, in cses where the lbor-tory denomintor dt is referring to specific hospitl(with ptient dys vilble), clcultion of the culturerte for tht hospitl is possible. Similrly, hving AMRdt referring to specific hospitl (with ptient dysvilble) would enble clcultion the MRSA rte fortht hospitl.

However, looking into the vilble dt, this ssump-tion seems not lwys correct. Some hospitls reserved by more thn one lbortory; it occurs minlyin UK (where the hospitl code often refers to trustinsted of single hospitl), but there re exmples lsoin Irelnd nd Hungry. The impliction of the reltionone hospitl to more thn one lbortory is tht, if onehospitl is reported in the AMR nd denomintor dtwhile only one of the lbortories serving this hospitl isreported, then the culture rte nd the MRSA incidencerte will be underestimted.

4.5 Hospital denominatorinformationThe totl number of hospitl beds for the hospitlsreporting AMR results nd providing denomintor dtin different countries rnged from 74 in Mlt to

43 433 in Frnce, reflecting the size of the country swell s the rte of prticiption to EARS-Net nd the rteof response to the questionnires. The proportion ofICU beds over totl hospitl beds shows wide vritionccording with the country, rnging from % in UK to 9%in Cyprus. The medin length of sty ws 6.6 dys with minimum in UK (3.4 dys) nd mximum in Mlt (.7dys). The nnul occupncy rte ws 7% or higher in out of countries (Tble 4.).

4.6 Hospital characteristicsBoth the size of hospitl nd the level of specilis-

tion cn influence the proportion of resistnce. As cnbe seen from Tble 4. nd Figure 4., the distribu-tion of size nd specilistion level of hospitls vried

4 EARS-Net laboratory/hospital denominatordata 2009


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Figure 4.1: Number of laboratories and hospitals reporting AMR and/or denominator data in 2009

3 3 4

UK

SI

PT

PL

MT

LV

LT

IT

IE

HU

FR

EE

DE

CY

BG

Denomintor informtion only

AMR informtion only

AMR nd denomintor informtion

Countrycode

Number of hospitls

UK

SI

PT

PL

MT

LV

LT

IT

IE

HU

FR

EE

DE

CY

BG

Denomintor informtion only

AMR informtion only

AMR nd denomintor informtion

Co

untrycode


A)

B)


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Table 4.1: Hospital denominator data for 2009

CountryHospitals reporting(denominator/AMR

data)Total number of beds Proportion of ICU

beds (%)Annual occu pancy

rate (%)Median length of

stay (days)IQR length of stay

(days)

Bulgaria (20/22) 9 326 8 77 6.3 5.46.9

Cyprus (5/5) 1 313 9 72 5.5 5.45.7Estonia (13/14) 4 989 6 75 6.4 5.17.0

France (231*/242) 143 433 5 83 7.7 6.49.2

Germany (47/173) 18 897 6 73 7.1 6.79.1

Hungary (62/65) 40 749 2 76 7.8 6.59.6

Ireland (52/71) 12 175 3 87 5.8 4.67.1

Italy (25/25) 15 358 5 84 - -

Latvia (11/12) 5 251 2 68 6.8 5.67.4

Lithuania (22/30) 9 792 4 75 7.0 6.38.1

Malta (3/3) 1 274 5 85 12.7 5.438.6

Poland (30/30) 15 045 2 70 5.5 4.46.2

Portugal (23/25) 10 885 5 79 7.3 5.58.6

Slovenia (12/12) 6 559 5 79 5.4 4.86.2

United Kingdom (50/142) 60 775 1 74 3.4 2.76.1

* 78 hospitls in Frnce reported dt for six-month period.

Table 4.3: Laboratory denominator information for 2009

Country Laboratories reporting(denominator/AMR data)

Number of hospitals* Total number of blood culture sets Number of blood culture sets per patient days

Bulgaria (18/20) 20 19 855 7.5

Cyprus (5/5) 5 12 991 37.6

Estonia (9/11) 11 11 691 10.7

Germany (6/17) 28 38 466 14.7

Hungary (26/27) 60 83 624 7.8

Ireland (37/43) 51 184 985 47.8

Italy (25/25) 25 125 577 26.8

Latvia (10/12) 10 7 859 6.2

Lithuania (12/13) 20 15 618 6.1

Malta (1/1) 3 4 879 12.4

Poland (30/30) 30 82 521 21.6

Portugal (21/22) 23 158 902 50.7

Slovenia (9/9) 12 46 040 24.2

United Kingdom (10/72) 10 95 017 45.2

* Number of hospitls served by lbortories repor ting denomintor dt.

Table 4.2: Hospital characteristics for 2009

CountryHospitals reporting

(denominator/AMR data)Proportion of hospitals by level of care (%)

Tertiary level Secondary level Primary level Other Unknown

Bulgaria (20/22) 50 35 5 10 0

Cyprus (5/5) 20 20 40 20 0

Estonia (13/14) 31 38 23 0 8

France (231/242) 22 78 0 0 0

Germany (47/173) 23 32 30 15 0

Hungary (62/65) 50 29 15 6 0

Ireland (52/71) 17 52 12 17 2

Italy (25/25) 68 28 4 0 0

Latvia (11/12) 36 55 0 0 9

Lithuania (22/30) 41 55 5 0 0Malta (3/3) 33 33 0 33 0

Poland (30/30) 13 77 10 0 0

Portugal (23/25) 57 26 4 13 0

Slovenia (12/12) 17 50 17 17 0

United Kingdom (50/142) 6 20 6 18 50

Primry level or district hospitl = hs f ew specilties, limited lbortory services; bed cpcity rnges from 3 to beds.Secondry level, or provincil hospitl = highly differentited by function with five to clinicl specilties; bed cpcity rnging from to 8 beds.Tertiry level or centrl/regionl hospitl = highly specilised stff nd technicl equipment; clinicl services re highly differentited by function; my hveteching ctivities; bed cpcity rnges from 3 to beds.Other = hospitls for specif ic ptient popultion, like militry hospitl, or hospitls with ny single specilty, like burns unit.Unknown = not vilble.


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considerbly between the reporting countries. This doesnot necessrily reflect different distributions of the ori-gin of EARS-Net blood cultures per country, becusenot ll hospitls contribute evenly to the EARS-Netdtbse. On the other hnd, this diversity cn indicte

differences in cse-mix, which my confound compri-son of AMR results between countries.

The type of hospitl nd the size of hospitl re notlwys linked nd it is not rre, especilly in smll coun-tries, tht university hospitls hve less thn beds.

4.7 Laboratory denominatorinformationIn 9, the number of blood culture sets processed inthe EARS-Net lbortories responding to the question-nire ws 888 . The medin culturing frequency ws

8. blood culture sets per ptient dys in 9.The highest rte ws reported by Portugl (.7) ndthe lowest by Lithuni (6.). For the mjority of thereporting countries, only minor chnges in the numberof blood culture sets tken per ptient dys (Tble4.3) ws observed when compring 8 dt to 9.The most significnt chnge ws observed for the UKnd my originte from the incresing number of report-ing hospitls ( in 8 nd in 9).

The BSIs scertinment is strongly linked to the bloodculture rte. Therefore, the very wide rnge of culturerte observed in the countries providing denomintor

dt could hve implictions on inter-country com-prison of both the incidence rte of infections, whichcould be underestimted in some countries, nd of theproportion of resistnce. In prticulr, the proportion ofresistnce could be overestimted if there is frequent

use of empiric therpy lso for invsive infections, nd ifthe cultures re more likely to be performed in ptientsnot responding to the empiric tretment.

4.8 ConclusionsIn summry, the sitution s ssessed from denomin-tor dt reported in 9 is similr to 8, with onlyfew chnges. For future improvement of the denomintordt collection nd nlysis, it is importnt to ddressthe following issues:

increse the number of countries reporting denomin-tor dt;

increse the number of hospitl nd lbortories pr-ticipting within countries;

improve the dt qulity for the vrible HospitlId(unique identifier for the hospitl within ech lbor-tory); nd

improve the estimtion of the coverge of the EARS-Net surveillnce, e.g. by using estimtions done tthe ntionl level bsed on knowledge of the country-specific sitution.

Figure 4.2: Proportion of small, medium and large hospitals per country, based on the number of beds, for all hospitalreporting both antimicrobial resistance data and denominator data in 2009

4 6 8

UK (/4)

SI (/)

PT (3/)

PL (3/3)

MT (3/3)

LV (/)

LT (/3)

IT (/)

IE (/7)

HU (6/6)

FR (3/4)

EE (3/4)

DE (47/73)

CY (/)

BG (/)

Smll hospitls ( beds)

Medium hospitls ( beds)

Lrge hospitls (> beds)

Countrycodes(responding/allhospitalsprovidingAMRdata)

Proportion of hospitls


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5.1Streptococcus pneumoniae5.1.1 Clinical and epidemiological importance

Streptococcus pneumoniae is common cuse of dis-ese, especilly mong young children, elderly peoplend ptients with compromised immune functions. Theclinicl spectrum rnges from upper irwy infections,such s sinusitis, nd otitis medi to pneumoni ndinvsive bloodstrem infections nd meningitis. SinceS. pneumoniae is the most common cuse of pneumoniworldwide, morbidity nd mortlity re high nd nnu-lly pproximtely 3 million people re estimted to die

of pneumococcl infections.

Pneumococci crry vriety of virulence fctors thtfcilitte dherence nd trnscytosis of epithelil cells.The cell wll of pneumococci is coted with viscouspolyscchride slime lyer termed the cpsule. This isthe most importnt virulence fctor becuse it protectsthe bcteri from the dhesion of opsonising ntibodiesnd the destruction by leucocytes. Cpsulr polysc-chrides re highly diverse nd ply n importnt rolein immune evsion. Around 8 different serotypes hvebeen described. The serotype distribution vries withge, disese nd geogrphicl region. Interestingly,serotypes most frequently involved in pneumococcldisese or colonistion in infnts re lso most fre-quently ssocited with ntimicrobil resistnce.

5.1.2 Resistance mechanisms

Bet-lctm ntibiotics bind to cell wll synthesisingenzymes, so clled penicillin-binding proteins (PBPs)nd interfere with the biosynthesis nd remodelling ofthe bcteril cell wll during cell growth nd division.The mechnism of penicillin resistnce in S. pneumo-niae consists of ltertions in PBPs, which results inreduced ffinity to this clss of ntibiotics. Altertionsin PBPs occur in stepwise fshion tht cuses dif-ferent degrees of resistnce proceeding from reduced

susceptibility through low-level clinicl resistnce conventionlly termed intermedite1 (I) to full cliniclresistnce (R). Although intermeditely resistnt strinsre clerly less susceptible thn sensitive strins, inbsence of meningitis, infections with these strins reoften successfully treted with high doses of penicillinor other bet-lctm compounds.

Mcrolide, lincosmine nd streptogrmin (MLS)ntibiotics re chemiclly distinct, but ll bind to ribosoml subunit inhibiting the initition of mRNAbinding nd thus ct s protein synthesis inhibitors. In

Microorgnisms re defined s intermedite by level ofntimicrobil ctivity with uncertin clinicl effec t. Occsionlly, thiscn be overcome if ntibiotics cn be dministered t higher dosend/or re concentrted t t he infected body site.

S. pneumoniae two resistnce mechnisms ginst MLSntibiotics

1011 sur annual ears net 2009

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