earss annual report 2003 - european centre for disease...
TRANSCRIPT
EARSS Annual Report 2003
• The European Antimicrobial Resistance Surveillance System (EARSS) is funded by DGSANCO of the European Commission and the Dutch Ministry of Health, Welfare and Sports.The project is co-ordinated by the National Institute of Public Health and the Environment(RIVM) of the Netherlands.
• It is the remit of EARSS to maintain a comprehensive surveillance and information system thatlinks national networks by providing comparable and validated data on the prevalence andspread of major invasive bacteria with clinically and epidemiologically relevant antimicrobialresistance in Europe.
• EARSS performs on-going surveillance of antimicrobial susceptibility in Streptococcuspneumoniae, Staphylococcus aureus, Escherichia coli, Enterococcus faecalis and Enterococcusfaecium causing invasive infections and monitors variations of antimicrobial resistance in timeand from place to place.
• By December 2003, 791 microbiological laboratories serving approximately 1300 hospitalsfrom 28 countries had provided susceptibility data for over 178,000 bacterial isolates.
• An interactive Website where regularly updated details can be found on resistance levels forimportant groups of antibiotics is available at http://www.earss.rivm.nl.
Period of data collection: January 1999 – December 2003
This document was prepared by the EARSS Management Team, members of the Advisory Board,and national representatives of EARSS, Bilthoven, The Netherlands, Septemer 2004.
ISBN number: 90-6960-118-4
Funded by the European Commission and the Dutch Ministry of Health, Welfare and Sports
under Agreement Number -2003212
Contractor RIVM (Rijksinstituut voor Volksgezondheid en Milieu)National Institute of Public Health and the Environment
EARSS thanks both the European Commission and the Dutch Ministry of Health, Welfare and Sports
for their financial support.
Neither the European Commission nor any person acting on its behalf is liable for the consequences of any use made of this information.
Contents
Why EARSS? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
List of abbreviations and acronyms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
The EARSS network in 2003 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Chapter 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
Chapter 2. The EARSS objectives and operational strategy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17Objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17Operational strategy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
Organisation of the EARSS network . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17The national networks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18Collecting and processing antimicrobial susceptibility test (AST) results . . . . . . . . . 19Laboratories . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19National representative and national data manager . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19International data manager at EARSS-MT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19Feedback from EARSS/RIVM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
Chapter 3. Quality and comparability of antimicrobial susceptibility test (AST) results: The EARSS external quality assurance exercise 2003 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .21Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .21Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .22Results and discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .22Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .26
Chapter 4. The antimicrobial resistance (AMR) situation in Europe in 2003 . . . . . . . . . . . . . . . . . . . . . . . 27Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27Results and discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
Streptococcus pneumoniae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28Staphylococcus aureus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34Enterococci . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36Escherichia coli . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
Chapter 5. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
CONTENTS 3
Appendix A. Country Summary Sheets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
Explanatory notes on the Country Summary Sheets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51Austria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54Belgium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .56Bulgaria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58Croatia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60Czech Republic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62Denmark . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64Estonia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66Finland . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68France. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70Germany . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72Greece . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74Hungary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76Iceland . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78Ireland . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80Israel . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82Italy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84Luxembourg . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86Malta . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88Netherlands . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90Norway . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92Poland . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .94Portugal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .96Romania . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .98Slovakia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .100Slovenia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .102Spain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .104Sweden . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .106United Kingdom . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .108
Appendix B. Technical notes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .111
4 CONTENTS
Why EARSS?
When in the last decades of the nineteenth century, pioneering microbiologists crushed what wasknown as the miasma theory (toxic vapours as the origin of epidemic diseases), one of the mostrevealing explanatory models in contemporary science had won the day. The imprint that thediscoveries by Pasteur, Koch and others had on mankind and it’s understanding was probably onlyequalled by Darwin’s and Wallace’s theory of natural selection. It was also quickly understood thatcombating infectious diseases could be accomplished by chemical substances targeted at thecausative organisms themselves and Paul Ehrlich’s dream of ‘magic bullets’ became a surprisingreality by the successive discovery of sulpha drugs and Fleming’s, Florey’s and Chain’s work onpenicillin. An apparently endless stream of newly identified antimicrobial compounds in the threedecades that followed the first successful treatment with penicillin left the impression that humanityhad once and for all, established superiority over the microbial kingdom. And indeed achievementswere impressive. Before the availability of antimicrobial chemotherapy over 50% of the overallburden of disease was still caused by infectious diseases in Europe and the US alike. With the adventof antibiotics and its congeners, epidemic infections seemed to melt away like ice in the sunshine.A few evolutionary biologists and social scientists remained however sceptical on the sustainabilityof the antimicrobial miracle. The former argued that with growing availability of antibioticcompounds, large scale emergence of resistance would only be a matter of time and the latter pointedto the fact that demographic transition as well as changes in lifestyles that shaped the societies inadvanced market communities after World War II, was equally if not more important than allvaccination, disinfection and antibiotic chemotherapy in reducing infectious diseases; and that areversal of these social improvements would rapidly translate into re-emergence of major epidemics.
Forty years on, we are confronted with a 22-year-old AIDS pandemic that has killed more peoplethan any single epidemic in history. We see MDR-TB, multidrug-resistant malaria (P. falciparum),quinolone- and beta-lactam-resistant Shigella and Salmonella, community-acquired methicillin-resistant Staphylococcus aureus (MRSA), the first reports of glycopeptide high-level resistanthospital MRSA and next to complete antibiotic resistance in Acinetobacter baumannii andPseudomonas aeruginosa. At the same time the once copious supply with new or improved anti-infective compounds has worn thin, as drug developers invest in more lucrative markets. With thishindsight, it is not surprising that 21st century infectious diseases consultants and public healthspecialist have become more modest in their claims to combat infectious diseases, as they witnessthe relentless upwards move of antimicrobial resistance on the public health agenda.
EARSS has been devised as the first publicly funded monitoring tool for antimicrobial resistance inthe European Region and indeed worldwide, able to provide official, validated and comparableresistance data for five major indicator bacteria. Designed as a surveillance network, it does not byitself control antimicrobial resistance but it provides the transparency and trend analysis needed forthe public awareness to a problem that could reverse some of the major accomplishments in modernmedicine.
The EARSS Management Team is thankful to all laboratories that continuously provide their routinesusceptibility data to the EARSS network for their joint effort, which shows their commitment tocontribute to the sustainability of the antimicrobial miracle.
Acknowledgement 5
I also wish to thank UK-NEQAS for its major role in preparing and organising the essential externalquality assurance (EQA) exercises in close cooperation with the members of the EARSS EQAcommittee. I would like to express my gratitude to all members of the EARSS Advisory Board andthe European Society for Clinical Microbiology and Infectious Diseases for sharing their expertise,for their contribution to this report and also for making the activities organised within EARSSsuccessful during the past year. Furthermore, I would like to thank John Stelling for visiting manyparticipating countries to give WHONET support for EARSS.
Finally, I would like to thank the funding bodies, The European Commission and the Dutch Ministryof Welfare and Sports for their support of this professional collaborative effort and the well-functioning network, which in 2004 includes almost 800 laboratories in 28 countries. I look forwardto continuing this fruitful cooperation for many years to come.
Hajo Grundmann EARSS Project Leader
Department of Infectious Diseases EpidemiologyNational Institute of Public Health and the Environment
6 Acknowledgement
Summary
The European Antimicrobial Resistance Surveillance System (EARSS) is an international networkfunded by the Directorate General for Health and Consumer Protection (DG SANCO) of theEuropean Commission and the Dutch Ministry of Health, Welfare and Sports. It maintains acomprehensive surveillance and information system that links national networks by providingcomparable and validated data on the prevalence and spread of major invasive bacteria withclinically and epidemiologically relevant antimicrobial resistance in Europe.
EARSS is co-ordinated by the Dutch National Institute of Public Health and the Environment(RIVM), and since it’s beginning in 1999, it has steadily drawn in new participants from all overEurope. By December 2003, 791 laboratories serving almost 1300 hospitals in 28 Europeancountries took part in this initiative. Together, they provide health care for an estimated populationof more than 100 million inhabitants. The EARSS database contains AMR data on approximately178,000 invasive isolates of five pathogens (Streptococcus pneumoniae, Staphylococcus aureus,Escherichia coli, Enterococcus faecalis, and Enterococcus faecium). It is thus the mostcomprehensive public health effort that describes and analyses geographic and secular trends inAMR and the only publicly funded initiative of this kind worldwide. Since 2000, EARSS has beenorganising external quality assessment (EQA) exercises of antibiotic susceptibility testing incollaboration with UK NEQAS (United Kingdom National External Quality Assessment Scheme),Centre National de Référence des Antibiotiques (CRAB) and the members of the EQA committee.In 2003 this exercise could again demonstrated that, countries participating in EARSS are capableof delivering susceptibility data of satisfactory quality illustrating that routinely reported results ascollected by EARSS have sufficient accuracy to provide good estimates of overall resistanceprevalences and trends.
The high proportion of erythromycin resistance (18%) among invasive S. pneumoniae isolates ofwhich (35%) was due to dual resistance with penicillin is remarkable. At the same time there areearly indications that penicillin resistance in invasive S. pneumoniae declines in some of thecountries that previously reported high rates. MRSA (methicillin-resistant S. aureus) rates varylargely over Europe. Trends are consistent with those reported in previous EARSS annual reports,indicating a steady rise in most countries including those with hitherto low overall resistance rates,whereas in the United Kingdom and Ireland the increase of MRSA reported during 1999-2001seems to even out. For the majority of countries the proportion of vancomycin-resistant E. faeciumisolates remained ≤ 5%, but 4 countries reported resistance above 15%. A widespread developmentof declining effectiveness of fluoroquinolones in E. coli at times when fluoroquinolones havebecome one of the most frequently prescribed antibiotic class has been recorded. This developmentbecomes accentuated by the finding of increasing resistance against 3rd generation cephalosporins.Certainly, infections with E. coli are becoming increasingly difficult to treat with the spectre ofserious therapeutic limitations in the future.
The EARSS 2003 annual report would not have been possible without the financial support ofDG SANCO of the European Commission Agreement Number - 2003212 and
the Dutch Ministry of Health, Welfare and Sports.
Summary 7
8 Annual report EARSS 2003
List of abbreviations and acronyms
AMR Antimicrobial resistance ARMed Antibiotic resistance surveillance and control in the Mediterranean regionAST Antimicrobial susceptibility testingBSAC British Society for Antimicrobial ChemotherapyBSI Blood stream infectionCA-SFM Comité de l’Ántibiogramme de la Société Française de MicrobiologieCRAB Centre National de Référence des AntibiotiquesCRG Commissie Richtlijnen GevoeligheidsbepalingenCZECH Czech Republic antimicrobial susceptibility guidelineCSF Cerebrospinal fluidDCFP Data check and feedback programDEFS Data Entry & Feedback SoftwareDG SANCO Directorate General for Health and Consumer ProtectionDIN Deutsche Industrie NormEARSS European Antimicrobial Resistance Surveillance SystemEARSS-MT EARSS Management TeamENSP Erythromycin non-susceptible Streptococcus pneumoniaeEQA External quality assuranceESAC European Surveillance of Antimicrobial Consumption ESBL Extended-spectrum beta-lactamaseESCMID European Society of Clinical Microbiology and Infectious DiseasesESGARS ESCMID Study Group for Antimicrobial Resistance SurveillanceEUCAST European Committee on Antimicrobial Susceptibility TestingFIRE Finnish study group for Antimicrobial ResistanceFREC Fluoroquinolone-resistant Escherichia coliGISA Glycopeptide intermediate resistant Staphylococcus aureusHLR High-level resistanceICU Intensive care unitMENSURA Mesa Espanola de Normalización de la Sensibilidad
y Resistencia a los AntimicrobianosMIC Minimal inhibitory concentrationMRSA Methicillin-resistant Staphylococcus aureusNCCLS (American) National Committee for Clinical Laboratory Standards NWGA Norwegian Working Group on AntibioticsPNSP Penicillin non-susceptible Streptococcus pneumoniaeRIVM Rijksinstituut voor Volksgezondheid en Milieu
(National Institute for Public Health and the Environment)SAR Self-medication with antibiotics and resistanceSRGA Swedish Reference Group for AntibioticsUK-NEQAS United Kingdom National External Quality Assessment Scheme for MicrobiologyVRE Vancomycin-resistant enterococciWHO World Health OrganizationWHONET WHO microbiology laboratory database software
Annual report EARSS 2003 9
EARSS Management Team in 2003
Project Leader: Hajo Grundmann Coordinator and International Data Manager Paul SchrijnemakersEpidemiologists Nienke Bruinsma and Edine TiemersmaData Manager and Software Engineer Jos MonenManagement Assistant Carola SchinkelConsultant Medical Microbiologist John Degener
E-mail: [email protected] Post: National Institute for Public Health and the Environment (RIVM)
Antonie van Leeuwenhoeklaan 9PO Box 13720 BA BilthovenThe Netherlands
Phone: +31 30 274 40 68Fax: +31 30 274 44 09
For general information and direct access to the EARSS database, see www.earss.rivm.nl
The EARSS Network in 2003
Countries participating in EARSS in 2003Austria ATBelgium BEBulgaria BGCroatia HRCzech Republic CZDenmark DKEstonia EEFinland FIFrance FRGermany DEGreece GRHungary HUIceland ISIreland IE
Israel ILItaly ITLuxembourg LUMalta MTNetherlands NLNorway NOPoland PLPortugal PTRomania ROSlovakia SKSlovenia SISpain ESSweden SEUnited Kingdom UK
10 Annual report EARSS 2003
EARSS Advisory Board members in 2003
Name On behalf of Country ProfessionFernando Baquero ESGARS Spain MicrobiologistMichael Borg EARSS national representatives/ARMed Malta EpidemiologistGiuseppe Cornaglia ESCMID Italy MicrobiologistWaleria Hryniewicz EARSS national representatives Poland MicrobiologistGunnar Kahlmeter EUCAST Sweden MicrobiologistHelmut Mittermayer EARSS national representatives Austria MicrobiologistWolfgang Witte EARSS national representatives Germany Microbiologist
EARSS QA Committee in 2003
G. Cornaglia Universitá degli Studi di Verona, Istituto de Microbiologia, ItalyJ. Degener Department of Medical Microbiology, Groningen University Hospital,
The Netherlands H. Grundmann Department of Infectious Diseases Epidemiology, RIVM, The NetherlandsG. Kahlmeter Central Hospital Växjö, SwedenJ. Mouton Canisius Wilhelmina Hospital, Nijmegen, The Netherlands P. Schrijnemakers Department of Infectious Diseases Epidemiology, RIVM, The NetherlandsC. Walton Quality Assurance Laboratory, Central Public Health Laboratory,
United Kingdom
EARSS National Representatives in 2003
Other parties and representatives:
ESCMID G. CornagliaESGARS F. BaqueroEUCAST G. KahlmeterWHO P. JenkinsWHONET J. StellingUK-NEQAS C. Walton
Annual report EARSS 2003 11
Austria (AT)H. MittermayerW. Koller
Belgium (BE)H. GoossensE. Hendrickx
Bulgaria (BG)B. Markova
Croatia (HR)S. KalenicA.TambicAndrasevic
Czech Republic(CZ)P. Urbaskova
Denmark (DK)D. Monnet
Estonia (EE)P. Naaber
Finland (FI)O. Lyytikäinen A. Nissinen
France (FR)H. Aubry-DamonV. Jarlier
Germany (DE)W. Witte U. Buchholz
Greece (GR)N. LegakisG. Vatopoulos
Hungary (HU)M. Füzi
Ireland (IE)D. IgoeO. Murphy
Iceland (IS)K. Kristinsson
Israel (IL)R. Raz
Italy (IT)A. PantostiP. D'Ancona
Luxembourg(LU)R. Hemmer
Malta (MT)M. Borg
Netherlands(NL)E. Tiemersma A. de Neeling
Norway (NO)A. HoibyG. Simonsen
Poland (PL)W. Hryniewicz
Portugal (PT)M. Caniça
Romania (RO)I. Codita
Slovakia (SK)L. Langsadl
Slovenia (SI)M. GubinaJ. Kolman
Spain (ES)F. BaqueroJ. Campos
Sweden (SE)B. Liljequist
UnitedKingdom (UK)A. Johnson T. Lamagni
12 Annual report EARSS 2003
EARSS data collection (national data managers or contact persons of national networks)
Contact Institute Country National surveillance network (URL)
person
S. Metz Elisabethinen Hospital Linz Austria EARSS Austria
E. Hendrickx Scientific Institute of Belgium EARSS Belgium www.iph.fgov.be/
Public Health
J. Verhaegen Catholic University of Leuven
M. Struelens Free University of Brussels
D. Pièrard Free University of Brussels
H. Velinov ‘Alexandrovska’, Laboratory for
B. Markova Clinical Microbiology, Sofia Bulgaria EARSS Bulgaria earss.online.bg
S. Kalenic Clinical Hospital Centre
Zagreb Croatia EARSS Croatia
V. Jakubu National Institute of Czech National Reference Laboratory for Antibiotics
B. Mackova Public Health Republic www.szu.cz/cem/earss/czeanj.htm
D. L. Monnet Statens Serum Institut Denmark DANMAP www.ssi.dk (for DANMAP reports
see: www.vetinst.dk/high.asp?page_id=138)
K. Kermes Tartu University Clinics Estonia EARSS Estonia [email protected]
T. Möttönen National Public Health Institute Finnish Hospital Infection Program (SIRO)
A. Nissinen (KTL) Finland Finnish Study Group for
Antimicrobial Resistance (FiRe)
www.ktl.fi/siro; www.ktl.fi/extras/fire/index.html
D. Trystram National Institute of France ONERBA
L. Gutmann Public Health Surveillance National Reference Centre for pneumococci
and E. Varon (InVS) www.onerba.org, www.invs.sante.fr
U. Buchholz Robert Koch Institute Germany EARSS Germany
A. Vatopoulos Department of Microbiology, Greece The Greek System for the Surveillance of
National School of Public Health Antimicrobial Resistance (WHONET Greece)
www.mednet.gr/whonet/
S. Vegh National Centre for Hungary EARSS Hungary www.antsz.hu
Epidemiology
L. Helgadottir Landspitali University Iceland
Hospital
S. Murchan National Disease Ireland EARSS Ireland www.ndsc.ie
Surveillance Centre
R. Raz Ha’Emek Medical Centre Israel EARSS Israel
H. Edelstein
F. D'Ancona Istituto Superiore di Sanità Italy AR-ISS www.simi.iss.it/antibiotico_resistenza.htm
A. Pantosti
O. Courteille National Service Luxembourg
of Infectious Diseases EARSS Luxembourg
E. Scicluna Infection Control Unit,
St. Luke's Hospital Malta EARSS Malta www.slh.gov.mt/ICUnit
Annual report EARSS 2003 13
Contact Institute Country National surveillance network (URL)
person
A. Bosman National Institute of Public Health
and the Environment Netherlands Electronic laboratory surveillance in the Netherlands
A. de Neeling Resistance surveillance project www.isis.rivm.nl
G.S. Simonsen University Hospital of Norway NORM
North Norway/
National Institute of Public Health
P. Grzesiowski National Institute of Public Health
Poland OPTY www.cls.edu.pl/surveillance
M. Caniça National Institute of Health Portugal
P. Lavado Dr. Ricardo Jorge GEMVSA/EARSS Portugal
I. Codita National Institute for Research Romania EARSS Romania
C. Balotescu and Development in Microbiology
and Immunology Cantacuzino
L. Langsadl National Institute for TB and Slovakia EARSS-Slovakia www.nutarch.sk
Respiratory Diseases
J. Kolman Institute of Microbiology and Slovenia EARSS Slovenia
M. Gubina Immunology, Medical Faculty,
University of Ljubljana
J. Oteo Instituto de Salud Carlos III Spain EARSS Spain
B. Olsson-Liljequist Sweden SMI-ResNet www.smittskyddsinstitutet.se
L. Gezelius Swedish Institute for
Infectious Disease Control
L. Bishop Health Protection Agency United
Communicable Disease Kingdom UK EARSS
Surveillance network Collaborating Group www.hpa.org.uk
Chapter 1. Introduction
Antimicrobial resistance (AMR) threatens the effectiveness of successful treatment of infectionsand is a public health issue with local, national, and global dimensions. In subsistence economiessuch as developing countries, resistance frequently occurs in microorganisms that are very likely tocause disease even when healthy individuals become infected (so called obligate pathogens, such asthe causative agents of dysentery, typhoid fever, tuberculosis and malaria). As a result ofantimicrobial resistance, patients infected with such organisms do not improve in response toconventional chemotherapy and are left with an equivocal prognosis unless alternative treatmentoptions are available. Conversely, in more advanced market communities, antibiotic resistance hasuntil now remained mainly confined to opportunistic pathogens with moderate to low diseasecausing potential. These organisms are usually part of the normal bacterial flora of humans and onlycause disease when introduced into body sites that are normally free from bacterial colonisation e.g.when anatomical barriers are breached due to trauma or medical/surgical interventions or in patientswith immature or defective immune systems. For this reason, problems with resistant organism inEurope, the US, Australia, the Middle East, North Africa, South America, China and Japan aremainly seen in infants or in elderly, frail patients or those with complicating underlying illness andthe highest proportions of resistant bacteria are encountered in hospitals. Predicting the future ofantimicrobial resistance in these countries is difficult. In the best-case, increasing antimicrobialresistance will limit the ability of modern medicine to deliver complicated or live savinginterventions such as advanced surgery, organ transplantation, intensive care and cancer therapy. Inits worst outlook, pathogens with higher virulence may become resistant or resistant pathogens maydevelop higher virulence, posing a real threat to the healthy non-hospitalised segments of thepopulation. On numerous scientific meetings these consequences have been addressed and it hasbecome clear that monitoring trends in antimicrobial resistance is needed to identify the healththreats imposed by antimicrobial resistance.
During the ‘Microbial Threat Conference’, held in September 1998 in Denmark, it was concludedthat an ‘Effective European surveillance should be in place and must have the agreement and activeinvolvement of all participants’ (‘the Copenhagen Recommendations’ [1]). This conference led tothe foundation of the European Antimicrobial Resistance Surveillance System (EARSS), funded bythe Directorate General for Health and Consumer Protection (DG SANCO) of the EuropeanCommission and the Dutch Ministry of Health, Welfare and Sports. Since 1999, it has been the remitof EARSS to maintain a comprehensive surveillance and information system that links nationalnetworks by providing comparable and validated data about the prevalence and spread of majorinvasive bacteria with clinical and epidemiologically relevant AMR in Europe. In 2001, at a follow-up EU conference in Visby, Sweden, it was concluded that all Member States of the European Union(EU) shall join the EARSS initiative as a minimum requirement of national surveillanceprogrammes (‘the Visby recommendations [2]’) and during the Rome conference convened by theEU Commission Directorate for Research and Development in November 2003, is was made clearthat linking antimicrobial resistance with microbial ecology and improving the knowledge about it’scosts to European societies is essential for the development of effective control strategies [3].
EARSS is co-ordinated by the Dutch National Institute of Public Health and the Environment(RIVM), and since it’s beginning in 1999, it has steadily drawn in new participants from theEuropean countries. At present, 791 laboratories serving approximately 1300 hospitals in 28
CHAPTER 1 Introduction 15
European countries participate. Thus EARSS receives data from of an estimated population of 100million inhabitants served by the participating hospitals. The EARSS database contains AMR dataon approximately 180 000 invasive isolates of five species of indicator bacteria (Streptococcuspneumoniae, Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, andEscherichia coli). It is thus the most comprehensive public health effort that describes and analysesgeographic and secular trends in AMR worldwide.
EARSS has encouraged and helped sustain national surveillance efforts and the network is theperfect basis for an integrated public health approach for AMR containment in Europe. To this end,EARSS operates in close collaboration with other EU-financed projects: European Surveillance ofAntimicrobial Consumption (ESAC), Self-medication with Antibiotics and Resistance (SAR) andAntibiotic Resistance Surveillance and Control in the Mediterranean region (ARMed). There is aclose partnership between the European Society of Clinical Microbiology and Infectious Diseases(ESCMID) and two of the society’s sub committees, namely, the European Committee onAntimicrobial Susceptibility Testing (EUCAST) and the ESCMID Study Group for AntimicrobialResistance Surveillance (ESGARS).
This report presents an overview of activities, innovations and results of the EARSS network in2003. Chapter 2 summarises the objectives and operational strategy. Chapter 3 presents the resultsof the annual external quality assurance (EQA) exercise for the year 2003. Chapter 4 provides adescriptive analysis of the situation of AMR in the European region. Chapter 5 summarises theoverall conclusions based on these results. The appendixes contain detailed country summary sheets(appendix A) and a technical section (appendix B). Results are based on data recorded from January1999 - December 2003, if not otherwise indicated.
References
1. V. Thamdrup Rosdahl and K. Borge Pederson (eds.). Report from the invitational EUConference on the microbial threat, Copenhagen, Denmark, 9-10 September 1998.
2. Progress Report on Antimicrobial Resistance, Visby, Sweden: Social Styrelsen, the SwedishNational Board of Health and Welfare, June 2001. Available at http://www.sos.se/FULLTEXT/123/2001-123-68/2001-123-68.pdf.
3. Report from the European Conference on the Role of Research in Combating AntibioticResistance, 2003 (2004). Clinical Microbiology & Infection 10: 473 - 497
16 CHAPTER 1 Introduction
Chapter 2. The EARSS objectives and operational strategy
ObjectivesIt is the public health purpose of EARSS to assist in the control of AMR; therefore, the followingobjectives have been defined:• To collect comparable and validated AMR data • To analyse trends in time and place (among various European countries) • To provide official national AMR data that constitute a basis for policy decisions • To provide feedback to ‘those who need to know’• To provide information about clinically and epidemiologically relevant AMR and to evaluate
interventions.
Furthermore, EARSS aims are:• To encourage the implementation, maintenance and improvement of national AMR surveillance
programmes to provide timely information for national policy decisions• To link AMR data to factors influencing the emergence and spread of AMR, particularly to
antibiotic use data, in close cooperation with the European Surveillance of AntimicrobialConsumption (ESAC)
• To initiate, foster and complement scientific research in Europe in the field of AMR.
At the start of the project, EARSS identified two bacterial species (S. aureus and S. pneumoniae)for which routinely generated antimicrobial susceptibility test (AST) results were collected. Thepathogens that subsequently became objects of surveillance were selected according toepidemiological (community versus hospital acquisition) and ecological (transmission versusselection) paradigms. At the same time, the occurrence of clinically and epidemiologicallymeaningful antibiotic resistance traits was determined for international comparison. The decision tocollect routine data meant that no changes to the regular diagnostic process were needed. Therefore,the participation of many laboratories has become feasible, and this has facilitated the probing of asubstantial part of the population in the participating countries. Sampling of the pathogens was andis restricted to invasive (blood culture and CSF) isolates, which are routinely tested for anti-microbial susceptibility in most laboratories. Data collection started in 1999 for S. pneumoniae andS. aureus after a preparatory phase in 1998. In 2001, the surveillance was extended to E. coli andenterococci (E. faecalis and E. faecium).
Operational strategy
Organisation of the EARSS networkEach participating country has appointed one or two national representatives. They are medicalmicrobiologists and/or infectious diseases epidemiologists. Moreover, each country has a nationaldata manager. The main task of the national representatives is to coordinate the EARSS-specificactivities of the participating laboratories (data collection, reporting, questionnaire completion andEQA strain and results distribution) and to communicate with the EARSS central database, whichis maintained and updated by the EARSS Management Team (EARSS-MT). The nationalrepresentatives also ensure that the laboratories generate their AST data according to the EARSS
CHAPTER 2 The EARSS objectives and operational strategy 17
protocols, as published in the EARSS manual 2004 (downloadable in pdf format from the officialEARSS website at www.earss.rivm.nl).
The main task of the national data manager is to collect, approve and forward resistance data eachquarter and to assist the national representative. Protocols for standardising the data collection havebeen developed with professional help from the European Society of Clinical Microbiology andInfectious Diseases (ESCMID) and WHO microbiology laboratory database software (WHONET).To assess the quality and comparability of AST data, an EQA exercise is carried out every year incollaboration with the UK-NEQAS, the Centre National de Référence des Antibiotiques (CRAB),and members of the EARSS-EQA committee (for more details, see Chapter 3). EARSS alsocontributes to the global strategy established by the World Health Organization (WHO) forworldwide surveillance of drug resistance (Figure 2.1).
The national networksIt is the task of the national representatives to select participating laboratories/hospitals that coverat least 20% of the total population and serve various types of institutions (university or tertiary carehospitals, general or district hospitals, rehabilitation centres or nursing homes, and others). Differentgeographic regions (urban/rural), and the socio-economic strata should be represented in an optimalmanner.
18
National Management Team
National Representative Data Manager
EARSS Management Team
DG-SANC O
NationalAdvisoryBoard
Advisory Board
Plenary Meeting
EQAcommittee8
WHO2
ESCMID3
EUCAST4
ESAC5
ARMed6
SAR7
LAB 1 LAB 2 LAB 3
Dutch Ministry of
Welfare & Sports
PUBLIC
ICMs1
Figure 2.1 Structure of the EARSS network 1 Intersectoral co-ordinating mechanisms, 2 World Health Organisation, 3 European Society for Clinical Microbiology
and Infectious Diseases, 4 European Committee on Antimicrobial Susceptibility Testing, 5 European Surveillance of
Antimicrobial Consumption, 6 Antibiotic Resistance Surveillance & Control in the Mediterranean countries, 7 Self-
medication of antimicrobial and resistance levels in Europe, 8 Committee on External Quality Assurance.
CHAPTER 2 The EARSS objectives and operational strategy
Collecting and processing antimicrobial susceptibility test (AST) resultsEARSS routinely collects susceptibility test results of invasive isolates and background informationabout patients. Laboratories are asked only to report the first isolate from blood or cerebrospinalfluid (CSF) per patient per reporting quarter. For optimal data collection EARSS requires specificinformation on the bacterial isolate, host, institution and laboratory that submits the resultsaccording to the specifications of the EARSS exchange format (EARSS manual 2004). AST resultsare generated and reported as specified by standard EARSS protocols. Furthermore, optional dataare collected; they include clinical diagnosis, other conditions, and facultative susceptibility data foradditional antibiotics. The EARSS manual 2004 can be downloaded in pdf format from the officialEARSS website at www.earss.rivm.nl.
LaboratoriesParticipating laboratories can opt for one of two ways of submitting data: electronically or bysending in conventional isolate record forms (on paper). EARSS provides various free softwaretools for electronic data handling, downloadable from the Website at www.earss.rivm.nl: (1) WHONET, the microbiology laboratory software, adapted for EARSS by John Stelling, and(2) Data Entry & Feedback Software (DEFS), which was developed as an exclusive EARSS tool.Laboratories are asked to collect AST data on a routine basis and to forward them to the nationalrepresentative or data manager quarterly. Before submission, laboratories are asked to check theirdata for: • Adherence to the EARSS protocol• Microbiological consistency/plausibility• Consistency with clinical breakpoints, sensitive (S), intermediate (I) and resistant (R)
breakpoints as defined by the specific guideline used (Each guideline is subject to revision bynational guideline committees, see Chapter 3).
National representative and national data managerAt the national level, the national data manager, in consultation with the national representative,processes the data. This is done in a stepwise fashion:• Recording data from all participating laboratories.• Manual data entry if isolate record forms are used. • Merging data from all participating laboratories into one single file.• Converting data to EARSS exchange format (EARSS manual 2004). • Revising data with the Data Check and Feedback Programme (DCFP).• Approval of data by the national representative (adherence to EARSS protocol, check for
microbiological consistency, and check whether the S, I and R interpretations agree with theminimal inhibitory concentrations (MICs) reported.
• Data transfer to EARSS-MT at the end of each quarter (March, June, September and December).
International data manager at EARSS-MTAfter receiving the data from the national data manager, the files are examined by the internationaldata manager of EARSS-MT. This process involves the following steps:
• Checking the data format• Inspection of the contents of the files • Removing duplicate reports• Determining resistance proportions
CHAPTER 2 The EARSS objectives and operational strategy 19
• Identification of unusual or rare results• Compiling of a feedback report summarizing the results • After approval by National Representative: data are added to the database, and the results are
made public on the EARSS website at www.earss.rivm.nl
Feedback from EARSS-MTAccurate and timely feedback is important for surveillance systems. Once data become available toEARSS-MT, they are processed and returned in a standard feedback report to the nationalrepresentative in order to obtain confirmation and final approval of validity and completeness of thedata. This feedback step also informs the national representatives of the occurrence of resistancepatterns with particular public health importance (MRSA, PNSP, VRE, GISA and ESBLs).Subsequently, the national co-ordinator is asked to confirm the correctness of the results. With his/her approval, the data will be added to the EARSS database and will become immediately availableon the interactive EARSS Website at www.earss.rivm.nl, where they can be displayed in variousdownloadable formats, such as tables, figures, and maps.
Furthermore, the data from the EARSS database are used to prepare annual reports, newsletters andpublications that are disseminated to the participants, the scientific community, policy makers anda broader public.
20 CHAPTER 2 The EARSS objectives and operational strategy
Chapter 3. Quality and comparability of antimicrobialsusceptibility test results: The EARSSexternal quality assurance exercise 2003
Introduction
Methods of antimicrobial susceptibility testing (AST) and differences in national guidelinesbetween European laboratories may affect the comparability of interpretative results based onclinical breakpoints in various ways. In order to validate the usefulness and comparability of highlyaggregated data it is therefore indispensable that laboratories participate in EQA schemes. Since2000, EARSS has been organising external quality assessment (EQA) exercises of antibioticsusceptibility testing in collaboration with UK NEQAS (United Kingdom National External QualityAssessment Scheme), Centre National de Référence des Antibiotiques (CRAB), under theprofessional guidance of the members of the EQA committee. The rationale of these EQA exercisesis, i) to assess the ability of participating laboratories to identify AMR of clinical and public healthimportance, ii) to determine the accuracy of quantitative susceptibility test results reported byindividual laboratories and iii) to decide on the overall comparability of routinely collected testresults between laboratories and countries and thus provide the means for justifying the pooling andcomparison of AST data across Europe.
CHAPTER 3 Quality and comparability of antimicrobial susceptibility test results 21
0
20
40
60
80
100
120
AT BE BU CZ DE DK EE ES FI FR GR HR HU IE IL IS IT LU MT NL PL PT RO SE SI SK UK
Countries
Nu
mb
er
of
lab
ora
tori
es in
vite
d
did not participate
participated
Figure 3.1 Participation in the 2003 external quality assurance (EQA) exercise.
MethodsIn September 2003, UK-NEQAS distributed a set of six strains to the laboratories participating inEARSS that were provided by the ‘French Reference Centre for Antibiotics-Institut Pasteur’ and theCanisius Wilhelmina Hospital, Nijmegen, The Netherlands (Table 3.1). The strains were charact-erised and tested by the two reference laboratories in France and The Netherlands and additionallyby two laboratories in the United Kingdom appointed by UK-NEQAS. Each reference laboratoryidentified the minimal inhibitory concentrations and provided results according to breakpointsrecommended by different national guidelines such as: CA-SFM, CRG/NCCLS, and BSAC (see listof abbreviations and acronyms on page 8). The reference laboratories agreed on a referenceinterpretation as an acceptable test result of each compound-pathogen combination (Table 3.1). Thestrains were distributed by UK-NEQAS to 737 laboratories participating in EARSS, and thelaboratories were asked to report species identification, methods and guidelines used, and clinicalsusceptibility results (S, I, R) according to their routine laboratory procedures. Results were consi-dered ‘concordant’ if the susceptibility results agreed with the designated reference interpretation.
Results and DiscussionIn Figure 3.1 the number of participating laboratories returning reports specified per country isshown. As in the previous years, the overall response rate was extremely satisfactory (91%). Theadherence to guidelines, by number of laboratories per country is shown in Table 3.2. The majority(72%) of laboratories used NCCLS guidelines. Most laboratories used E-test for the determinationof MICs (86%). Of the laboratories that used automated laboratory systems (n = 197), VITEKsystems were most frequently utilised (59%).
22 CHAPTER 3 Quality and comparability of antimicrobial susceptibility test results
CHAPTER 3 Quality and comparability of antimicrobial susceptibility test results 23
Table 3.1 Reference laboratory results: MICs, susceptibility as determined by the reference laboratories
(reference interpretation), and overall concordance
Reference laboratory Reference Overall
range (MICs in mg/L) interpretation concordance (%)
Specimen U2A 166 S. aureus
Species identification 99
Oxacillin 0.25 - 0.5 S 99
Gentamicin ≤ 0.5 S 99
Erythromycin 0.25 - 0.5 S 98
Tetracycline 0.25 - 0.5 S 99
Rifampicin < 0.016 S 99
Vancomycin 1 - 2 S 100
Teicoplanin 0.25 - 1 S 100
Penicillin 0.016 - 0.064 S 96
Ciprofloxacin 1 S 85
Cefoxitin 1 - 2 S 99
Specimen U2A 1786 S. aureus (mecA positive)
Species identification 100
Oxacillin 2 - 4 R 81
Gentamicin 0.12 -0.5 S 98
Erythromycin > 128 R 99
Tetracycline 0.25 - 1 S 99
Rifampicin ≤ 0.016 S 100
Vancomycin 1 - 2 S 99
Teicoplanin 0.25 - 2 S 99
Penicillin 8 - 64 R 98
Ciprofloxacin ≥ 16 R 94
Cefoxitin 4 - 16 R 78
Specimen U2A 961 S. pneumoniae
Species identification 98
Oxacillin 0.064 S 97
Penicillin-G ≤ 0.016 S 98
Ceftriaxone 0.016 S 98
Cefotaxime 0.016 S 99
Ciprofloxacin 1 S/I* 84
Erythromycin 8 - 16 R 96
Clindamycin 0.125 - 0.5 S 95
Table continues on next page
24 CHAPTER 3 Quality and comparability of antimicrobial susceptibility test results
Reference laboratory Reference Overall
range (MICs in mg/L) interpretation concordance (%)
Specimen U2A 1787 S. pneumoniae
Species identificatio 99
Oxacillin 2 I/R* 86
Penicillin-G 0.25 I 77
Ceftriaxone 0.064 - 0.125 S 98
Cefotaxime 0.016 - 0.064 S 96
Ciprofloxacin 0.5 - 1 S/I* 88
Erythromycin 0.064 - 0.125 S 98
Clindamycin 0.125 - 0.5 S 99
Specimen U2A 1789 E. coli
Species identification 99
Ampicillin > 256 R 97
Gentamicin 1 S 99
Tobramycin 16 R 80
Ciprofloxacin 0.008-0.016 S 99
Cefotaxime ≥16 I/R* 91
Ceftriaxone ≥16 I/R* 90
Ceftazidime >256 R 91
Piperacillin >256 R 93
Piperacillin/Tazobactam 2 S 76
ESBL positive 94
Specimen U2A 604 E. gallinarum (vanC positive)
Species identification 51
Amoxicillin NT S 97
Ampicillin 0.5-2 S 99
Vancomycin 16 I/R* 58
Gentamicin 8 Non-HLR** 97
Teicoplanin 0.5-1 S 98
* Depending on the guideline used
** Investigated for high-level resistance to aminoglycosides.
For the S. aureus strain U2A166, the overall concordance was > 95% for all antibiotic compoundstested, except for ciprofloxacin (85%, Table 3.1). The S. aureus strain U2A1786 was mecA positiveand heterogeneously expressing this resistance determinant. This MRSA strain (sequence type 45 orBerlin strain) has caused hospital outbreaks in The Netherlands and Germany due to this ‘stealth’resistance behaviour. Only 81% of the laboratories identified the oxacillin-resistance of this MRSAstrain correctly. Another rare feature of this strain was the low specificity of the cefoxitin test,otherwise known to be a good screening test for MRSA [1]. These results underline the importanceof a high degree of suspicion where quinolone-resistance and/or erythromycin resistance isidentified in what prima vista appears to be a MSSA isolate. Strains of this nature are difficult to
CHAPTER 3 Quality and comparability of antimicrobial susceptibility test results 25
Table 3.2 Guidelines used by laboratories
Guideline*
Country BSAC CA-SFM CRG CZECH DIN FIRE MENSURA NCCLS SRGA > 1 Other** Missing Total
AT 11 11
BE 1 72 4 3 19 99
BU 21 3 24
CZ 1 8 5 28 2 44
DE 8 4 3 1 7 23
DK 3 2 5
EE 9 1 10
ES 2 29 2 7 40
FI 2 9 4 15
FR 20 2 22
GR 1 40 5 46
HR 23 3 26
HU 29 1 30
IE 2 14 7 3 26
IL 5 5
IS 2 2
IT 48 1 8 57
LU 6 1 2 9
MT 1 1
NL 5 14 3 2 24
PL 52 6 1 10 69
PT 18 2 3 23
RO 1 17 1 2 7 28
SE 22 22
SI 11 11
SK 11 4 15
UK 22 9 2 11 6 50
Total 25 22 5 8 8 2 3 460 25 57 27 95 737
* For explanation of acronyms, see page 8
** Including Stokes method
detect, which partly explains their success as epidemic clones in hospitals. The concordance forgentamicin, vancomycin, teicoplanin, penicillin and ciprofloxacin was ≥ 94% (Table 3.1).
S. pneumoniae strain U2A961 was characterised by an erythromycin efflux mechanism. This traitwas correctly detected by 94% of laboratories (Table 3.1). S. pneumoniae strain U2A1787 wasintermediately resistant to penicillin, which was correctly detected by only 77% of the laboratories(Table 3.1). Instead of identifying penicillin intermediate susceptibility correctly, 12% of thelaboratories called this strain penicillin-resistant. This feature may lead to an overprescription ofalternative antibiotics, such as macrolides and may lead to a further increase in resistance to thisantibiotic class as currently observed in many European countries. The ESBL expressed by the E.coli strain U2A1789 was correctly identified by 94% of the laboratories (Table 3.1). However, 10%of the laboratories failed to detect cefotaxime/ceftriaxone resistance associated with ESBL-pro-duction. This type of ESBL (SHV-5) has become very prevalent in Europe in the past 15 years andis mostly encountered in Klebsiella pneumoniae, rendering host cells highly resistant to ceftazidime.Rather unexpectedly, 20% of the laboratories also missed the tobramycin resistance in the same E.coli strain.
Specimen U2A604 was an Enterococcus gallinarum with a vanC resistance. The identification ofenterococci by automated systems is notoriously unreliable, as pigment production and motility arenot identified by these instruments. Sadly, only 51% of the laboratories were able to identify thespecies correctly. Most laboratories (90%) identified reduced susceptibility to vancomycin (I = 58%/ R = 32%) and susceptibility to teicoplanin, which is typical for vanC resistance (Table3.1).
Conclusions
The fourth EARSS external quality assessment showed that laboratories participating in EARSS arein general capable of delivering susceptibility data of good quality. However, 19% of laboratoriesfailed to detect an epidemic MRSA known to cause outbreaks in hospitals. The strain is difficult todetect due to the fact that the resistance phenotype is heterogeneously expressed. However,laboratories should take this opportunity to re-evaluate the methodology used for the detection ofMRSA.
Twenty-three per cent of laboratories failed to correctly categorize penicillin non-susceptibility in S.pneumoniae. In the E. coli strain 20% missed overt tobramycin resistance and although 94%identified the ESBL phenotype, 10% missed the cefotaxime/ceftriaxone resistance. The results showthat there is room for re-evaluation, calibration and improvement of methodology. At the same timethey illustrate that routinely reported results as collected by EARSS in most instances havesufficient accuracy to provide good estimates of overall resistance prevalences and trends.
References1 Skov, R., Smyth, R., Clausen, M. et al. (2003). Evaluation of a cefoxitin 30 µg disc on Iso-Sensitest agar for detection of methicillin-resistant Staphylococcus aureus, Journal of AntimicrobialChemotherapy 52, 204-207
26 CHAPTER 3 Quality and comparability of antimicrobial susceptibility test results
Chapter 4. The antimicrobial resistance situation in Europe in 2003
Introduction
European countries are characterised by a high degree of diversity, be it cultural, economic, orsocial. The heterogeneity of values and administrative strategies is reflected by different health careseeking behaviour and fundamentally different health care systems; all of which influence theemergence, dissemination, and introduction of infectious diseases caused by antibiotic-resistantorganisms in a complex manner.
During the past five years (1999-2003), EARSS has collected antimicrobial susceptibility test(AST) results of invasive isolates of five bacterial species that serve as indicators for thedevelopment of AMR in Europe. The species included are S. pneumoniae, S. aureus, E. coli, E.faecalis, and E. faecium. At the end of 2003, the EARSS database contained information on 178,040isolates from 791 laboratories serving 1300 hospitals in 28 countries. This chapter will discuss thecurrent dimension and pertinent trends of antimicrobial resistance that became visible by the end of2003. We also report the demographic characteristics of patients for whom antibiotic-resistantindicator organisms were reported to EARSS.
Methods
In table 4.1 clinically and epidemiologically relevant antibiotic compound-pathogen combinationsrequired for EARSS reporting are listed. For all five pathogens, laboratories determined andinterpreted their susceptibility results according to national or international guidelines as S(sensitive), I (intermediately resistant), and R (resistant), using routine procedures. AST breakpointsfrom the different guidelines used by participating laboratories can be found on the EARSS websiteat www.earss.rivm.nl.
Table 4.1. Pathogens and antibiotic compounds
Pathogen Antimicrobial susceptibility
S. pneumoniae Penicillin non-susceptibility, defined as Pen I or Pen R
Erythromycin resistance
S. aureus Methicillin resistance
E. faecalis/ E. faecium Vancomycin non-susceptibility
Aminoglycoside high-level resistance (HLR)
E. coli Ampicillin resistance
3rd generation cephalosporin (cefotaxime, ceftriaxone and ceftazidime) resistance
Fluoroquinolone (ofloxacin or ciprofloxacin) resistance
Aminoglycoside (gentamicin or tobramycin) resistance
Data analysis of AST results reported and approved by the National Representatives and DataManagers was carried out using SAS software (SAS Institute Inc, Cary, NC, USA, release 8.02).
CHAPTER 4 The antimicrobial resistance situation in Europe in 2003 27
The countries represented in the maps had to report at least 10 isolates of a specific pathogen in2003. For trend analysis a Cochran-Armitage trend test was used, considering only the laboratoriesthat permanently provided data from 2000 through 2003 for S. aureus and S. pneumoniae and from2001 through 2003 for E. coli, E. faecalis and E. faecium. In addition, at least 20 isolates per yearhad to be reported per country to be included into the analysis for trend.
Results and discussion
Streptococcus pneumoniae
Streptococcus pneumoniae is the single most important cause of community-acquired pneumoniaand acute otitis media and is one of the most important pathogens leading to bloodstream infectionsand meningitis in children and adults. Increasing prevalence of resistant strains in the past 15 yearsis now threatening the successful treatment of these infections [1, 2]. Country-specific resistanceproportions were shown to be associated with antibiotic prescription habits [3], which emphasisesthe importance of judicious antibiotic use and the possible need for alternative control strategiessuch as vaccination.
Penicillin non-susceptibilityBetween 1999-2003, 653 laboratories from 26 countries reported susceptibility results for 30,374invasive S. pneumoniae isolates to EARSS, of which 93% were recovered from blood cultures. The average proportion of penicillin non-susceptibility was 10% for all isolates reported in 2003. InFigure 4.1 the proportions for penicillin non-susceptible S. pneumoniae (PNSP) in 2003 by countryare illustrated in a map format with different colours indicating various levels of resistance. Thehighest proportions of penicillin non-susceptibility were observed in the Mediterranean countries(Figure 4.1). Most of the penicillin non-susceptible invasive S. pneumoniae isolates (79%) showedintermediate resistance to penicillin. Infections caused by these strains can still be treated withappropriately dosed beta-lactams. The ratio between penicillin intermediate (I) and full resistance(R) differed largely between countries. Countries that reported the highest proportions of fullresistance were Romania (19%), Poland (19%), Bulgaria (11%), and Spain (10%, Figure 4.2).
From 2000 to 2003, an increase of penicillin non-susceptibility was observed in Sweden (from 2%to 5%) and in Austria (from 2% to 11%). Austria reported low numbers of isolates each year (whenconsidering only the laboratories that permanently provided data from 2000 through 2003 for trendanalysis). This limitation in sample size warrants caution when interpreting the results for the wholecountry. A decrease in the proportion of fully penicillin-resistant isolates from 2000 to 2003 wasobserved in Belgium (from 5% to 1%), Ireland (from 4% to 2%), Spain (from 11% to 8%), and theUK (from 5% to 3%). Even though this decreasing trend was only significant for Belgium, it is unlikely that thissimultaneous development has happened by chance alone.
28 CHAPTER 4 The antimicrobial resistance situation in Europe in 2003
Figure 4.1 Streptococcus pneumoniae: invasive isolates non-susceptible to penicillin (PNSP) in 2003.
Figure 4.2 Streptococcus pneumoniae: invasive isolates with intermediate and full resistance to penicillin reported for the
entire EARSS observation period (all isolates with reported penicillin susceptibility were included).
CHAPTER 4 The antimicrobial resistance situation in Europe in 2003 29
< 1%No data
1 – 5%5 – 10%10 – 25%25 – 50%> 50
LU MT
0%
5%
10%
15%
20%
25%
30%
35%
40%
45%
RO
(32
)
IL(5
27
)
ES
(25
45
)
HU
(23
1)
PT
(64
8)
HR
(19
8)
PL
(32
)
SI(
46
9)
LU
(14
7)
BE
(55
46
)
IE(1
24
1)
SK
(49
)
BG
(76
)
IT(9
11
)
FI(
17
86
)
IS(2
10
)
CZ
(61
3)
UK
(32
25
)
MT
(44
)
AT
(33
6)
DK
(18
88
)
SE
(41
42
)
NO
(41
6)
DE
(11
19
)
NL
(38
76
)
EE
(67
)
Country (number of isolates)
Pro
po
rtio
n
resis
tan
t
% resistant
% intermediate
Erythromycin resistanceAST results for erythromycin were reported for 24,980 of the isolates (82%). Erythromycin resistance is more frequent (18%) than penicillin non-susceptibility (10%) andfollows the same geographical pattern in Europe (Figure 4.3). Significant changes were remarkablefor Finland, which showed an increase in erythromycin resistance from 9% to 18%. This trend isknown and was already reported in 2002 by the Finnish surveillance system FINRES [4] butremained unabated in 2003. Austria also witnessed a similar trend from 4% to 16% which tallieswith the increase penicillin-non-susceptibility in laboratories that reported for the entire observationperiod to EARSS. The predominance of erythromycin resistance in most European countriesindicates that either selective constraints due to the amount of macrolide consumption favours theemergence and spread of this phenotype or the fact that acquisition of macrolide resistancedeterminants are less costly to the ecological fitness than target modification of penicillin bindingprotein that result from DNA recombination events.
Figure 4.3 Streptococcus pneumoniae: invasive isolates resistant to erythromycin (ENSP) in 2003.
Single and dual resistance to penicillin and erythromycinIn 2003, the proportion of single non-susceptibility to penicillin among isolates collected from allparticipating laboratories in Europe was 5%, whereas erythromycin single resistance was 12%. Dualresistance to both erythromycin and penicillin (I+R) was 6%. Figure 4.4 shows the proportion ofpenicillin and/or erythromycin resistance by country for the aggregated 1999-2003 data set. Thehighest proportions of dual resistance were found in Spain (18%; CI95 17-20%), Luxembourg (12%;CI95 7-18%), Hungary (12%; CI95 8-17%), Israel (11%; CI95 8-14%), and Belgium (10%; CI95 9-11%). High proportions were also found in Romania (16%; CI95 5-36%) and Poland (18%; CI95 6-
30 CHAPTER 4 The antimicrobial resistance situation in Europe in 2003
< 1%No data
1 – 5%5 – 10%10 – 25%25 – 50%> 50
LU MT
37%), but the low numbers of isolates resulted in wide confidence intervals and render conclusionsdifficult (Figure 4.4). On the basis of the recorded resistance developments (until 2002), EARSS used a nominalregression model to extrapolate the pertinent trends and concluded that single non-susceptibility topenicillin will further decrease, while erythromycin resistance and dual resistance will increase ifthe ecological forces that shape the current population structure will remain unchanged [5].
Figure 4.4 Streptococcus pneumoniae: invasive isolates with dual resistance to penicillin and erythromycin and single
resistance to erythromycin and penicillin reported for the entire EARSS observation period (penicillin-resistant isolates
include both intermediate and fully resistant isolates).
Demographic characteristicsSimilar proportions of single and dual resistance were observed between male and female patientsfor identical age groups. The highest proportions of single resistance (both substances) and dualresistance to penicillin (I+R) and erythromycin has been recorded for the age group less than fiveyears of age (Figure 4.5). It is known that the paediatric age group is most vulnerable to pneumo-coccal infections [2, 6, 7], which is substantiated by the highest relative number of S. pneumoniaeisolates reported to EARSS in the under five-years-olds. It appears that this age group represents thereservoir for antibiotic-resistant pneumococci, and thus extra benefit might be expected, if it couldbe shown that protein conjugate vaccine is able to reduce carriage in young children.
Figures 4.6 A and B show the relative proportions of single and dual resistance by age group andcountry. The illustration also shows that the highest percentage of erythromycin resistance (bothsingle erythromycin and dual resistance) was consistently reported for the youngest age groups bymost of the countries. This may be a consequence of common prescribing of oral paediatricerythromycin formulation.
CHAPTER 4 The antimicrobial resistance situation in Europe in 2003 31
0%
5%
10%
15%
20%
25%
30%
35%
40%
45%
ES
(24
10
)
IL(5
00
)
RO
(25
)
IT(8
23
)
BE
(55
46
)
HU
(20
4)
MT
(42
)
HR
(18
7)
LU
(13
7)
PL
(28
)
PT
(21
6)
SI(
39
9)
IE(9
95
)
UK
(19
77
)
BG
(65
)
FI(
17
06
)
SK
(38
)
AT
(25
9)
DE
(84
5)
IS(1
94
)
DK
(18
88
)
SE
(32
72
)
CZ
(57
6)
NL
(25
91
)
EE
(57
)
Country (number of isolates)
Pro
po
rtio
n r
esis
tan
t
single ery
dual
single pen
Figure 4.5 Streptococcus pneumoniae: Proportion single and dual resistance to penicillin (I+R) and erythromycin by age
groups for the period 1999-2003.
ConclusionsNon-susceptibility to penicillins, with or without concomitant resistance to erythromycin, is stillhigh in many European countries. In Germany, Czech Republic, Estonia, the UK, the Netherlandsand most Scandinavian countries it is below 5% and for some hitherto unexplained reason the ratesin full penicillin resistance have been declining for several countries. However, the high overallerythromycin resistance, 18%, is remarkable (single erythromycin resistance 12% and dual peni-cillin and erythromycin resistance 6%). The marked differences in the distribution of single and dualpenicillin and macrolide resistance between countries is noteworthy, but not yet understood. Conservative use of macrolides is especially important in situations where penicillin and erythro-mycin resistance is common and appropriately dosed beta-lactams should remain the preferredempirical treatment. Vaccination, especially of young children may affect antibiotic resistance inpneumococcal disease in Europe. Whether vaccine use will slow the expansion of resistantpneumococci, or whether resistant strains not included in the vaccine will replace vaccine serotypes,remains to be explored.
32 CHAPTER 4 The antimicrobial resistance situation in Europe in 2003
0%
5%
10%
15%
20%
25%
< = 4 y (3334) 5-19 y (1051) 20-64 y (9123) > = 65 y (10620)
Agegroups (total number of isolates)
Pro
po
rtio
n r
esis
tan
t
single pen
dual
single ery
CHAPTER 4 The antimicrobial resistance situation in Europe in 2003 33
0%
10%
20%
30%
40%
50%
60%
70%
<=
4 y
(39
8)
5-1
9 y
(84)
20-6
4 y
(897)
>=
65 y
(992)
<=
4 y
(20
1)
5-1
9 y
(56)
20-6
4 y
(120)
>=
65 y
(119)
<=
4 y
(1079)
5-1
9 y
(307)
20-6
4 y
(1643)
>=
65 y
(2517)
<=
4 y
(96
)
5-1
9 y
(28)
20-6
4 y
(272)
>=
65 y
(282)
<=
4 y
(14
4)
5-1
9 y
(59)
20-6
4 y
(343)
>=
65 y
(432)
<=
4 y
(77
)
5-1
9 y
(25)
20-6
4 y
(164)
>=
65 y
(133)
<=
4 y
(21
0)
5-1
9 y
(78)
20-6
4 y
(867)
>=
65 y
(551)
Agegroups (number of isolates) by country
Pro
po
rtio
n r
esis
tan
t
single ery
dual
single pen
Spain Israel Belgium Italy Ireland Slovenia Finland
A
0%
10%
20%
30%
40%
50%
60%
70%
<=
4 y
(20
0)
5-1
9 y
(73)
20-6
4 y
(490)
>=
65 y
(733)
<=
4 y
(81
)
5-1
9 y
(24)
20-6
4 y
(355)
>=
65 y
(377)
<=
4 y
(15
4)
5-1
9 y
(42)
20-6
4 y
(735)
>=
65 y
(957)
<=
4 y
(21
1)
5-1
9 y
(69)
20-6
4 y
(904)
>=
65 y
(1322)
<=
4 y
(70
)
5-1
9 y
(48)
20-6
4 y
(285)
>=
65 y
(173)
<=
4 y
(16
4)
5-1
9 y
(74)
20-6
4 y
(1430)
>=
65 y
(1602)
Agegroups (number of isolates) by Country
Pro
po
rtio
n r
esis
tan
t
UK Germany Denmark Netherlands Czech R Sweden
B
single ery
dual
single pen
Figure 4.6 A/B Streptococcus pneumoniae: Proportion single and dual resistance to penicillin (I+R) and erythromycin
by age group per country for the period 1999-2003. Countries are displayed in descending order of resistance. (Only the
countries with at least 20 isolates in each age groups were included).
Staphylococcus aureus
Staphylococcus aureus is the main cause of bone, joint and soft-tissue infections acquired in hospitaland in the community. It also causes blood stream infections and endocarditis, and it is a frequentcause of food poisoning. S. aureus resistant to penicillinase-fast beta-lactam antibiotics such asmethicillin, oxacillin, cloxacillin, flucloxacillin, nafcillin and cephalosporins is conventionallytermed MRSA (for methicillin-resistant S. aureus) and is genetically determined by the presence andexpression of the mecA gene located within a staphylococcal cassette chromosome SCCmec thatinserts at a specific recombination site in the bacterial chromosome. MRSA has become a notoriouscause of hospital-acquired infections and thrives in hospitals worldwide [8, 9]. Recently, novelMRSA clones have been described that cause infections in the community. These are mainly skinand soft tissue infections caused by strains that express a particular virulence marker termed Panton-Valentin Leukocidin.
Methicillin resistanceBetween 1999-2003, 702 laboratories from 27 countries reported susceptibility results for 73,609 S.aureus blood isolates to EARSS. PCR detection of the mecA gene or MIC-values for oxacillin as aconfirmation of oxacillin-resistance were available for 68% of the reported isolates (n = 15,537).The geographical variation of MRSA in 2003 is shown in Figure 4.7. It demonstrates a north-southgradient, with the lowest MRSA prevalence in northern Europe and highest in southern Europe andIsrael, but also in the United Kingdom and Ireland. MRSA proportions varied almost 100-fold, withthe lowest proportion in Iceland (< 1%) and the highest proportion in Greece (51%).
Figure 4.7 Staphylococcus aureus: invasive isolates resistant to methicillin (MRSA) in 2003.
34 CHAPTER 4 The antimicrobial resistance situation in Europe in 2003
< 1%No data
1 – 5%5 – 10%10 – 25%25 – 50%> 50
LU MT
For the observation period 2000-2003, a significant increase in the proportions of MRSA wasobserved in Belgium, Germany, The Netherlands, Portugal and The United Kingdom. The increasereported by the Scandinavian countries is at a much lower level but the trend must be taken seriouslysince a low threshold for ‘losing control’ may exist but is not well defined. For the British Isles therelentless increase of MRSA proportions among bloodstream infections that occurred between 1992and 2000 seems to have petered out and consistent with the mandatory Staphylococcus aureusbacteraemia surveillance scheme in England and Wales, EARSS data show no further increase inthe last three years (Figure 4.8).
Figure 4.8 Staphylococcus aureus: invasive isolates resistant to methicillin (MRSA) from 2000 to 2003.
The proportion of outpatient samples increased from 7% in 2000 to 12% in 2003 (only consideringthe laboratories participating for the full period) (p trend < 0.0001), specifically in Northern coun-tries (Sweden, Denmark and the Netherlands) and Ireland and Belgium. Presently, the EARSSdatabase does not distinguish between certain clones or the expression of certain virulence markersand therefore it is impossible to decide whether this increase is due to the dissemination of hospitalMRSA among returning patients who are sampled in outpatient settings or due to an increase ingenuine community-acquired MRSA.
ConclusionsRates of MRSA in invasive infections vary between < 1% and 50% over Europe. The trends areconsistent with those reported in previous EARSS annual reports. The persistent increase, althoughat a low and much envied level, is worrying to the Scandinavian countries. The proportion of MRSAreported per year seems to have stabilised in the United Kingdom and Ireland, which might be theresult of increased efforts in these countries to contain the MRSA epidemic, or a saturation effect asa result of fitness thresholds that limit the spread of typically hospital-acquired MRSA outside
CHAPTER 4 The antimicrobial resistance situation in Europe in 2003 35
0%
10%
20%
30%
40%
50%
60%
AT
(275)
BE
(76
6)
BG
(86
)
CZ
(93
0)
DE
(43
0)
DK
(52
0)
ES
(81
6)
FI(
50
7)
GR
(21
4)
IE(6
97
)
IS(5
3)
IT(1
75
)
LU
(62
)
MT
(92)
NL
(12
38
)
PT
(273)
SE
(16
24
)
SI(
24
6)
UK
(15
24
)
Country (average nr of isolates per year)
Pro
po
rtio
n r
esis
tan
t
2000
2001
2002
2003
hospitals. Slovenia still shows decreasing MRSA proportions, which indicate that the interventionsimplemented in the last years still produce effects.
Enterococci
Among all EARSS indicator organisms, enterococci are regarded as the least virulent pathogens andare a constitutive part of the natural gut flora of vertebrates. When causing infections, enterococciare mainly involved in urinary tract infection and contribute to abdominal infections such asabscess-forming peritonitis. Despite their mainly benign habits, some lineages exist that haveaccumulated a genetic repertoire that make them particularly successful in the hospital environmentand may cause serious infections in debilitated patients. They can cause severe forms of endocarditisas well as blood stream or bone infections and occasionally meningitis. Their opportunisticbehaviour is complemented by an extreme ability to survive environmental stress such asdesiccation, temperatures up to 65°C, and they show some degree of tolerance to disinfectants. Bynature, enterococci are also resistant to many antibiotic compounds and they were the first gram-positive bacteria for which the acquisition of resistance to third-line glycopeptide antibiotics(vancomycin and teicoplanin) was described. Ever since, vancomycin-resistant enterococci (VRE)have served as the paradigm for the post-anti-microbial era [10].
Vancomycin non-susceptible Enterococcus faeciumBetween 2001-2003, 495 laboratories from 25 countries reported susceptibility results from 3931 E.faecium blood isolates to EARSS. The highest proportions of vancomycin non-susceptible E.faecium in 2003 were reported by Portugal (50%; n = 103), Italy (25%; n = 112), Greece (23%; n = 93), and Ireland (19%; n = 134) (Figure 4.9). As the number of E. faecium isolates reported issmall, trend analyses of the proportion of vancomycin non-susceptibility do not yield reliableconclusions.
High-level aminoglycoside-resistant Enterococcus faecalisAST results for high-level aminoglycoside were reported by 495 laboratories from 25 countries of12,065 E. faecalis blood isolates between 2001-2003. In 2003, the highest proportions of amino-glycoside high-level resistance among E. faecalis isolates were observed for Hungary (87%; totalnumber of isolates n = 69) and Greece (57%; n = 81) (Figure 4.10). From Iceland no high-levelresistance to aminoglycosides was reported, but this was only based on a total of 15 isolates.
Among the 10 countries that reported ≥ 20 E. faecalis isolates per year (after considering only thelaboratories that permanently provided data from 2001 through 2003), the Czech Republic observeda significant trend of increased high-level aminoglycoside resistance from 38% (n = 388) in 2001to 45% (n = 472) in 2003. A significant increase was also observed in Finland, 23% in 2001 (n =26) to 39% in 2003 (n = 72), and Israel, 24% in 2001 (n = 63) to 43% in 2003 (n = 196). On theother hand, a significant decrease was observed for Croatia, 48% in 2001 (n = 31) to 26% in 2003(n = 57). However, due to the low number of isolates leading to wide confidence intervals,conclusions should be drawn with caution.
36 CHAPTER 4 The antimicrobial resistance situation in Europe in 2003
CHAPTER 4 The antimicrobial resistance situation in Europe in 2003 37
< 1%No data
1 – 5%5 – 10%10 – 25%25 – 50%> 50
LU MT
Figure 4.9 Enterococcus faecium: invasive isolates non-susceptible to vancomycin in 2003*.
* Vancomycin non-susceptibility in E. faecalis is not displayed in the map as proportion for the majority of countries did
not exceed 1%.
< 1%No data
1 – 5%5 – 10%10 – 25%25 – 50%> 50
LU MT
Figure 4.10 Enterococcus faecalis: invasive isolates resistant to high-level aminoglycoside (gentamicin) in 2003.
Demographic characteristicsEnterococci were more frequently isolated from male patients (Table 4.2). The AMR proportionsdid not differ by gender. Only in young females (ageband 5-19 years) VRE and high-level amino-glycoside-resistant enterococci were more frequently isolated than in males of the same age whichmay reflect the higher proportion of bacteraemias originating from ascending urinary tract infect-ions in young females compared to males of the same age band.
ConclusionsVancomycin resistance appears to be still rare in E. faecalis and below 5% in E. faecium in mostcountries that contribute to the EARSS database. A complete picture for Europe can however notbeen provided as data from Bulgaria, Denmark, England, Norway, Northern Ireland, and Scotlandwere still not available in 2003. Nevertheless, four countries reported resistance proportions above15%. It appears that countries reporting high levels of VRE, are witnessing outbreaks of E. faeciumin several care facilities. The overall low number of isolates reported to EARSS does not yet permita country-specific trend analysis. High-level aminoglycoside resistance has become commonamong E. faecalis in all countries, the majority reporting levels between 25 and 50%.
Table 4.2 Proportion of antibiotic resistance by gender and age group.
Vancomycin non-susceptible E. faecium Aminoglycoside HL resistant E. faecalis
Age group � � � �
N %R N %R N %R N %R
≤ 4 y 117 4% 88 1% 295 14% 238 15%
5-19 y 35 6% 35 11% 66 27% 41 37%
20-64 y 803 7% 545 8% 1687 38% 944 33%
≥ 65 y 1024 5% 738 7% 2330 33% 1394 36%
Total 1979 6% 1406 7% 4378 34% 2617 33%
Escherichia coli
Escherichia coli is the most frequently gram-negative bacterium isolated from blood cultures inclinical settings. It is the most frequent cause of community and hospital-acquired urinary tractinfections. It is associated with spontaneous and surgical peritonitis, it causes synergistic woundinfections and it is one of the most important food-borne pathogens. Broad-spectrum penicillinssuch as ampicillin and amoxicillin were the treatment of choice before plasmid-coded TEM1 beta-lactamases became an almost ubiquitous component of genetic equipment of this species, andaminopenicillin resistance has exceeded 40% in most European countries. Since the early 90’sfluoroquinolones have been widely used for therapy of invasive enteric pathogens. For yearsfluoroquinolones have been effective in the treatment of infections caused by Escherichia coli, butrecently resistance has been spreading in several European countries, including countries withoverall low resistance levels [11-14].Between 2001-2003, 502 laboratories from 25 countries reported susceptibility results for 58,061invasive E. coli isolates to EARSS. Susceptibility test results for aminopenicillin, 3rd generationcephalosporins, fluoroquinolones, and aminoglycosides, were reported for 53,126 (92%), 55,086(95%), 52,899 (91%), and 56,501 (97%) respectively.
38 CHAPTER 4 The antimicrobial resistance situation in Europe in 2003
Aminopenicillin resistanceThe overall proportion of aminopenicillin resistance in Europe among invasive E. coli in Europe hasreached 47% in 2003. Sweden reported the lowest proportion of this type of resistance (28%),whereas Romania, Ireland and Israel reported > 60% (Figure 4.11). In the last three years (2001-2003), aminopenicillin resistance has remained relatively stable. Only in Germany a significantincrease was observed from 43% in 2001 to 48% in 2003 (p < 0.05).
Figure 4.11 Escherichia coli: invasive isolates resistant to aminopenicillin in 2003
3rd generation Cephalosporin resistanceAmong the four antibiotic groups under EARSS surveillance for E. coli, the lowest overallproportion of resistance was reported for 3rd gen. cephalosporins (3%). Nevertheless, highfrequencies were observed in Bulgaria (18%) and Romania (19%) (Figure 4.12). Furthermore,seven countries (AT, BG, CZ, DE, ES, HU and SE) witnessed a significant increase from 2001 to2003 (Figure 4.13). The overall spread of 3rd gen. cephalosporin resistance coincides with numerousreports of CTX-M ESBL in E. coli, and should serve as an early warning.
CHAPTER 4 The antimicrobial resistance situation in Europe in 2003 39
< 1%No data
1 – 5%5 – 10%10 – 25%25 – 50%> 50
LU MT
Figure 4.12 Escherichia coli: invasive isolates resistant to 3rd generation cephalosporins in 2003
Figure 4.13 Escherichia coli: invasive isolates resistant to 3rd gen. cephalosporins from 2001 to 2003.
40 CHAPTER 4 The antimicrobial resistance situation in Europe in 2003
< 1%No data
1 – 5%5 – 10%10 – 25%25 – 50%> 50
LU MT
0%
5%
10%
15%
20%
25%
AT
(35
0)
BE
(72
1)
BG
(93
)
CZ
(14
66
)
DE
(51
2)
EE
(63
)
ES
(19
21
)
FI(
12
89
)
GR
(42
9)
HR
(34
0)
HU
(29
9)
IL(7
90
)
IS(8
9)
LU
(18
9)
MT
(77
)
NL
(16
50
)
PL
(95
)
PT
(42
6)
SE
(29
37
)
SI(
39
7)
SK
(10
1)
Country (average number of isolates per year)
Pro
po
rtio
n r
esis
tan
t
2001
2002
2003
Fluoroquinolone resistanceIn 2003, Fluoroquinolone resistance was the second most prevalent phenotype after aminopenicillinresistance, reaching an average of 12.5% overall. Israel, Italy, Malta, Portugal, Spain and Slovakiareported fluoroquinolone resistance proportions of ≥ 20%. The lowest proportions were reportedfrom Finland and Estonia (5%) (Figure 4.14). This trend already observed from 2001 to 2002,continued in 2003 and was statistically significant in seven countries (AT, BG, CZ, DE, ES, HU,SE). At the same time it seems unlikely that sampling error could account for the statistically non-significant but consistent increase in eight other countries (Figure 4.15).
Figure 4.14 Escherichia coli: invasive isolates resistant to fluoroquinolones in 2003
Aminoglycoside resistanceAminoglycoside resistance is rare as a single resistance trait in E. coli. The proportion ofaminoglycoside-resistant E. coli in Europe is still quite low, with an average of 5%, but has reachedmore than 10% in Israel, Bulgaria, Romania, and Malta (Figure 4.16). In the last three years (2001-2003), aminoglycoside resistance has remained relatively stable. Only Finland witnessed anincrease, albeit at low levels from 0.2% in 2001 to 1.2% in 2003 (p < 0.05).
Combined resistanceIn total 46,948 of the 58,061 invasive E. coli isolates (81%) reported to EARSS were tested for all4 antibiotic classes included in the EARSS protocol. Overall 4% of these isolates were resistant to≥ 3 antibiotics reported to EARSS. Resistance to aminopenicillin + fluoroquinolone + amino-glycoside occurred in 2.5% of the E.coli. Approximately 1% of all isolates were resistant to all 4antibiotics reported to EARSS. (Table 4.3).
CHAPTER 4 The antimicrobial resistance situation in Europe in 2003 41
< 1%No data
1 – 5%5 – 10%10 – 25%25 – 50%> 50
LU MT
42 CHAPTER 4 The antimicrobial resistance situation in Europe in 2003
< 1%No data
1 – 5%5 – 10%10 – 25%25 – 50%> 50
LU MT
Figure 4.16 Escherichia coli: invasive isolates resistant to aminoglycosides in 2003
Figure 4.15. Escherichia coli: invasive isolates resistant to fluoroquinolones from 2001 to 2003.
0%
5%
10%
15%
20%
25%
30%A
T(3
32
)
BE
(62
1)
BG
(93
)
CZ
(14
70
)
DE
(50
3)
EE
(58
)
ES
(19
25)
FI(
12
84
)
GR
(43
1)
HR
(39
0)
HU
(28
2)
IL(7
91
)
IS(8
2)
LU
(17
9)
MT
(77
)
NL
(18
50
)
PL
(93
)
PT
(37
2)
SE
(25
43
)
SI(
39
7)
SK
(10
1)
Country (average number of isolates per year)
Pro
po
rtio
n r
esis
tan
t
2001
2002
2003
Fifty per cent of the invasive E.coli isolates were susceptible to the four drugs recorded in theEARSS database. A recent study on E.coli in urinary tract infections in Europe came to very similarconclusions. Just over half the isolates were susceptible to 12 antibiotic substances included in thatinvestigation [14]. However, figures suggested in the current analysis for single aminopenicillinresistance have to be used with caution as resistance to aminopenicillins is frequently coupled withresistance to trimethoprim and/or sulphonamide which is not reported by EARSS network [15].
Even though the prevalence of combined resistance to three or all four of the antibiotics reported toEARSS is still low in Europe (4%), five countries witnessed an increase over the last three years(BG, FI, HU, NL, and SE). Several countries that did not observe resistance to three or moreantibiotics in 2001, reported multiple combined resistance in the following two years (AT, FI, HU,and SE) (Figure 4.17). The countries with the highest proportions of combined resistance areBulgaria and Israel (> 15%). In Bulgaria the reporting is still increasing, whereas Israel reporteddecreasing figures in the past three years.
CHAPTER 4 The antimicrobial resistance situation in Europe in 2003 43
0%
5%
10%
15%
20%
25%A
T(3
27
)
BE
(45
4)
BG
(89
)
CZ
(14
65
)
DE
(49
9)
EE
(52
)
ES
(19
10
)
FI(
10
31
)
GR
(42
6)
HR
(39
0)
HU
(25
2)
IL(7
72
)
IS(8
1)
LU
(17
5)
MT
(76
)
NL
(15
69
)
PL
(91
)
PT
(36
8)
SE
(77
4)
SI(
39
7)
SK
(99
)
Country (average number of isolates per year)
Pro
po
rtio
n r
esis
tan
t
2001
2002
2003
Figure 4.17 Escherichia coli: invasive isolates with multiresistance (≥ 3 antibiotic groups) reported from 2001 to 2003.
Only the isolates with reported data for all 4 antibiotic groups were included.
Demographic characteristicsBoth the patient’s age and gender was available for 53,887 (93%) of all 58,061 E. coli isolatesreported to EARSS respectively. The overall age distribution of invasive E. coli isolates reported,clearly indicates that most E. coli blood strain infections are found among the elderly (≥ 65 years).Overall the E. coli isolates were more frequently isolated from female patients (56%) especiallyamong adults and elderly. In addition, women develop urinary tract infections more frequently thanmen, which will have a bearing on the occurrence of blood stream infections. Conversely, in theunder five-years-old, male patients were more frequent, indicating that at this age boys are morelikely to develop an invasive E. coli infection. The proportion of aminopenicillin, aminoglycoside, and 3rd gen cephalosporin resistance was com-parable between age groups and gender, whereas in the under five-year-olds fluoroquinoloneresistance was significantly lower compared to the older patients independent of gender (Table 4.4).In addition, above the age of five, fluoroquinolone resistance among males was significantly lowercompared to females (Table 4.4). The low resistance rates in those aged under five years confirmsrecently published findings [16] and could be explained by the restricted fluoroquinolone use ininfants.
44 CHAPTER 4 The antimicrobial resistance situation in Europe in 2003
Table 4.3 Single resistance and resistance combinations among invasive Escherichia coli isolates for the period 2001-2003
in Europe (n = 46,948).
Single resistance and resistance combinations Number (% of total)
Fully susceptible 23,653 (50.38)
Aminopenicillin 16,445 (35.03)
Fluoroquinolones 732 (1.56)
3rd gen. Cephalosporins 14 (0.03)
Aminoglycosides 172 (0.37)
Aminopenicillin + Fluoroquinolones 3,014 (6.42)
Aminopenicillin + 3rd gen. Cephalosporins 289 (0.62)
Aminopenicillin + Aminoglycosides 577 (1.23)
Fluoroquinolones + 3rd gen. Cephalosporins 1 (0.00)
Fluoroquinolones + Aminoglycosides 94 (0.20)
3rd gen. Cephalosporins + Aminoglycosides 2 (0.00)
Aminopenicillin + Fluoroquinolones + Aminoglycosides 1,181 (2.52)
Aminopenicillin + Fluoroquinolones + 3rd gen. Cephalosporins 231 (0.49)
Aminopenicillin + Aminoglycosides + 3rd gen. Cephalosporins 121 (0.26)
Aminopenicillin + Fluoroquinolones + Aminoglycosides + 3rd gen. Cephalosporins 422 (0.90)
Total 46,948 (100)
ConclusionE. coli is rapidly becoming a ‘difficult-to-treat’ organism in many countries. Aminopenicillin resist-ance is so high that it renders the drug useless for empirical therapy unless combined with anaminoglycoside. Resistance rates to fluoroquinolones and to 3rd generation cephalosporins are alsoincreasing and threaten to jeopardize the usefulness of these drugs too. A further disquieting trendis the increased finding of strains with co-resistance to several drugs.
References1. Moellering, R. C. (2002). The continuing challenge of lower respiratory tract infections.
Clinical Infectious Diseases 34, S1-3.2. Whitney, C. G., Farley, M. M., Hadler , J., et al. (2000). Increasing prevalence of multidrug-
resistant Streptococcus pneumoniae in the United States. New England Journal of Medicine343, 1917-24
3. Bronzwaer, S. L. A. M., Cars, O., Buchholz, U. et al (2002). A European study on therelationship of antimicrobial use and antimicrobial resistance. Emerging Infectious Diseases 8,278-82.
4. Pihlajamaki, M., Kaijalainen, T., Huovinen, P., et al. (2002). Rapid increase in macrolideresistance among penicillin non-susceptible pneumococci in Finland, 1996-2000. Journal ofAntimicrobial Chemotherapy 49, 785-92.
5. Bruinsma, N., Kristinsson, K. G., Bronzwaer, S., et al. (2004). Trends in penicillin and erythro-mycin resistance among invasive Streptococcus pneumoniae in Europe. Journal of Antimicro-bial Chemotherapy. In press.
6. Mbelle, N., Huebner, R. E., Wasas, A. D., et al. (1999). Immunogenicity and impact onnasopharyngeal carriage of a nonavalent pneumococcal conjugate vaccine. Journal of InfectiousDiseases 180, 1171-6.
7. Obaro, S. K., Adegbola, R. A., Banya, W. A., et al. (1996). Carriage of pneumococci afterpneumococcal vaccination. The Lancet 348, 271-2.
8. Diekema, D. J., Pfaller, M. A. , Schmitz, F. J., et al. (2001). Survey of infections due toStaphylococcus species: frequency of occurrence and antimicrobial susceptibility of isolatescollected in the United States, Canada, Latin America, Europe, and the Western Pacific regionfor the SENTRY Antimicrobial Surveillance Program, 1997-1999. Clinical Infectious Diseases32 (Suppl 2), S114-32.
CHAPTER 4 The antimicrobial resistance situation in Europe in 2003 45
Table 4.4 Proportion of antibiotic resistance by age group.
Aminopenicillin Fluoroquinolones* Aminoglycosides 3rd gen. Ceph
Age group N % N % N % N %
≤ 4 y 1701 49 1696 4 1694 7 1757 4
5-19 y 673 58 676 9 671 7 705 4
20-64 y 15881 49 16367 11 15960 5 16794 2
≥ 65 y 32066 44 33563 11 31807 5 34444 2
* For fluoroquinolones there was a small but significant difference (≤ 4%) between males and females. For the other
investigated drugs there were no differences between males and females.
9. Muto, C. A., Jernigan, J. A., Ostrowsky, B. E., et al. (2003). SHEA guideline for preventingnosocomial transmission of multidrug-resistant strains of Staphylococcus aureus andenterococcus. Infection Control and Hospital Epidemiology 24, 362-86.
10. Cohen ML. (1992) Epidemiology of drug resistance: implications for a post-antimicrobial era.Science 257, 1050-5.
11. Schmitz, F. J., Verhoef, J., Fluit, A. (1999). Geographical distribution of quinolone resistanceamong Staphylococcus aureus, Escherichia coli and Klebsiella spp. isolates from 20 Europeanuniversity hospitals. SENTRY Participants Group. Journal of Antimicrobial Chemotherapy 43,431-4.
12. Oteo, J., Campos, J., Baquero, F., et al. (2002). Antibiotic resistance in 1962 invasive isolates ofEscherichia coli in 27 Spanish hospitals participating in the European Antimicrobial ResistanceSurveillance System (2001). Journal of Antimicrobial Chemotherapy 50, 945-52.
13. Kresken, M., Hafner, D., Mittermayer, H., et al. (1994). Prevalence of fluoroquinolone resist-ance in Europe. Infection 22 (Suppl 2), S90-8.
14. Kahlmeter, G. (2003). An international survey of the antimicrobial susceptibility of pathogensfrom uncomplicated urinary tract infections: the ECO-SENS project. Journal of AntimicrobialChemotherapy 51, 69-76.
15. Kahlmeter, G. and Menday, P. (2003). Cross-resistance and associated resistance in 2478Escherichia coli isolates from the pan-European ECO-SENS project surveying the anti-microbial susceptibility of pathogens from uncomplicated urinary tract infections. Journal ofAntimicrobial Chemotherapy 52, 128-131.
16. Abelson Storby, K. Österlund, A. and Kahlmeter, G. (2004). Antimicrobial resistance inEscherichia coli in urine samples from children and adults: a 12 year analysis. Acta Pediatrica93, 487-491.
46 CHAPTER 4 The antimicrobial resistance situation in Europe in 2003
Chapter 5. Conclusions
The geographic diversity in antimicrobial resistance across Europe is evident and appears to followtime worn cultural boundaries. Although national borders are drawn along historical lines ofpolitical and military disposition, they may indeed circumscribe country-specific values includingbeliefs shared by patients and their doctors concerning the treatment of disease. Undeniably,European countries have different health care-, administration-, and reimbursement systems. Theseinfluence prescription and antimicrobial consumption patterns as well as infection control policiesin the community and health care facilities in various ways. Results illustrated in map formats asdisplayed by EARSS undoubtedly oversimplify the occurrence of antimicrobial resistance inEurope and are vulnerable to several types of bias. Thus the selection of hospitals varies betweenparticipating national networks, as does the number of laboratories, which if small, may not berepresentative for the country as a whole. Moreover, differences exist in antimicrobial susceptibilitytesting methodology and antimicrobial breakpoints between countries and laboratories, affecting theconsistency with which resistance is ascertained. Finally, diagnostic habits influence the reportingof resistance. Hospitals in which microbiological investigations are performed only after the initialempirical treatment has failed are bound to report higher resistance rates as institutions thatconventionally sample patients before the administration of antimicrobial chemotherapy.
Despite these differences between and within countries a credible overall picture emerges. Thenumber of participating laboratories is convincing and the fact that the number of countries andlaboratories continue to increase adds to the value of EARSS. Over 90% of all laboratoriesrepeatedly participate in the EARSS programs for external quality assessment. It is indisputable thatthis commitment to quality will continuously improve the accuracy and usefulness of thissurveillance initiative. The fourth EARSS external quality assessment showed that laboratoriesparticipating in EARSS are in general capable of delivering susceptibility data of good quality (over90% concordance between laboratories). However, when challenged with a difficult MRSA, 19%of the laboratories failed to detect an epidemic MRSA which had caused outbreaks in Dutch andGerman hospitals. The strain is notorious in that it is easily misclassified due to the fact that theresistance phenotype is heterogeneously expressed and this has probably contributed to its dissemi-nation in hospitals. All laboratories should take this opportunity to re-evaluate the methodologyused for the detection of MRSA. Twenty-three per cent of laboratories either over- or understatedpenicillin resistance in a penicillin non-susceptibility in S. pneumoniae. In the E. coli strain 20%missed overt tobramycin resistance and although 94% identified the ESBL phenotype, 10% missedthe cefotaxime/ceftriaxone resistance. The results show that there is room for re-evaluation, cali-bration and improvement of methodology. At the same time they illustrate that routinely reportedresults as collected by EARSS in most instances have sufficient accuracy to provide good estimatesof overall resistance prevalences and trends and that pooling of reported resistance data as done byEARSS is justified. Especially trend analyses for a stable and representative set of laboratorieswithin each country provide a reliable indication for resistance developments since diagnostichabits, methods and standards usually remain unchanged; and with a continuously growingdatabase, EARSS is able to report trends with increasing confidence.
In 2003 non-susceptibility to penicillins in S. pneumoniae with or without concomitant resistanceto erythromycin, was still high in many European countries. In Germany, Czech Republic, Estonia,the UK, the Netherlands and most Scandinavian countries the rate was still below 5%, and for some
CHAPTER 4 The antimicrobial resistance situation in Europe in 2003 47
hitherto unexplained reason penicillin resistance has been declining for several countries. However,the high overall erythromycin resistance remains remarkable (single erythromycin resistance 12%and dual Pen+Ery resistance 6%). The pronounced differences in the ratios of penicillin tomacrolide resistance between countries are noteworthy, but not yet understood. Conservative use ofmacrolides is especially important in situations where penicillin and erythromycin resistance iscommon and appropriately dosed beta-lactams should remain the preferred empirical treatment.Vaccination, especially of young children may affect antibiotic resistance in pneumococcal diseasein Europe. Whether vaccine use will slow the expansion of resistant pneumococci, or whetherresistant strains not covered by the vaccine will replace vaccine serotypes, remains to be explored.
For S. aureus rates of MRSA in invasive infections varied between < 1% and 50% in 2003. Thetrends are consistent with those reported in previous EARSS annual reports. The relentless increase,although at a low and much envied level, is reason for concern to the Scandinavian countries. Theproportion of MRSA reported per year seems to have stabilised in the United Kingdom and Ireland,which might be the result of increased efforts in these countries to contain the hospital MRSAepidemic, or a saturation effect as a result of fitness thresholds that limit the spread of MRSAoutside hospitals. Slovenia still shows decreasing MRSA proportions, which indicate that theinterventions implemented in the last years still produce effects.
In contrast to MRSA, which has become established at various endemic levels in many Europeanhospitals, epidemiology of vancomycin resistance was still unstable. In E. faecalis vancomycinresistance is low and it remained below 5% in E. faecium in most countries although 4 countriesreported resistance above 15%. Six countries that regularly provide AST data for S. pneumoniae andS. aureus were still unable to report data for enterococci by 2003 and conclusions drawn by EARSSremain incomplete for this important indicator organism. It appears that in countries reportinghigher levels of VRE, these were likely due to outbreaks of E. faecium in care facilities. The lownumber of reports did not permit far-reaching statistical conclusions. High-level aminoglycosideresistance has become frequent among E. faecalis in all countries, the majority reporting levelsbetween 25 and 50%.
E. coli is rapidly becoming a ‘difficult-to-treat’ organism in many countries. Aminopenicillin resist-ance has become so high that it renders the drug useless for empirical therapy unless combined withan aminoglycoside. Resistance rates to fluoroquinolones and to 3rd generation cephalosporins conti-nued to increase in 2003. The usefulness of these drugs in the empirical treatment of severeinfections is thus increasingly threatened. A further disquieting trend was the increased finding ofstrains with co-resistance to several drugs. Since E. coli is an important pathogen responsible formany hospital as well as community-acquired infections the steady increase of multiple-resistantstrains warrants a watchful eye.
CHAPTER 5 Conclusions’ 49
50 CHAPTER 5 Conclusions’
Appendix A. Country Summary Sheets
In the following appendix, country-specific resistance information is presented together withdenominator data and the characteristics of the participating laboratories and hospitals.
Explanation to the country summary sheets:
Table 1 and 2 and Figures 1 and 2 give an indication of the sample size and the representativenessof the country-specific resistance data available to EARSS. Table 1 displays results of the laboratories and hospitals that provided denominator data in 2002 (i.e.that responded to the questionnaire) and thus only includes the laboratories that reported AST resultsto EARSS in 2002, and provided blood culture information and the hospitals that reported ASTresults to EARSS in 2002, and provided their number of hospital beds. For details about thecalculation of the average annual occupancy rate, the estimated catchment population and thepercentage of the total population covered, we refer to the technical notes (Appendix B). If datawere not available this is stated as ‘na’.Figure 1 gives and indication about the degree of specialisation of the participating hospitals, andFigure 2 shows the geographic location of the laboratories reporting in 2003. The size of the dots inthe maps represents the number of laboratories in that area:
DotNumber of labs 1 5 10 15
Antibiotic resistance 1999-2003. Table 3 provides information on the proportion of invasivebacterial isolates not susceptible to the antibiotic classes mentioned in the EARSS protocols. Fromthe majority of all non susceptible S. pneumoniae and S. aureus isolates we received thecorresponding MIC or Etest result, according to the EARSS protocols, however for some of the nonsusceptible isolates this information is missing. Resistance proportions in Table 3 are based on thereported number of isolates given in Table 2. Table 4 gives details about the origin of the isolate (patient, source and hospital department). Theabbreviations used in this table stand for; PNSP = pencillin non-susceptible S. pneumoniae MRSA= methicillin-resistant S. aureus, FREQ = fluoroquinolone-resistant E. coli, and VRE = vanco-mycin-resistant (I+R) E. faecalis or E. faecium. If the number of isolates in a certain categoryaccounts for less than 0.5% of the total number of isolates, the percentage total is set at 0 and thepercentage resistance is not shown.
Local variation. Figures 3 and 4 show local variation in the proportions of PNSP and MRSA bydisplaying these by laboratory and by hospital, respectively. For both Figures, a minimum of 5 isolates and at least 2 years of participation in EARSS for eachlaboratory or hospital was required, before being included in the figure. The total number oflaboratories or hospitals (included in the figure), the minimum, maximum, median, 1st and 3rdquartile of the proportion of resistance is displayed in a box in the Figures. If an ‘X’ is displayed atthe end of a hospital code this means that the hospital code is not provided; consequently, this canencompass one or more unknown hospitals.
APPENDIX A 51
APPENDIX A 53
Countries
54 APPENDIX A
Table 1. Reference data of 2002
Total
Labs/Hosps reporting to EARSS 10/46
Labs/Hosps providing denom.data 10/33
Number of blood culture sets 29000
Number of hospital beds 21772
Average annual occupancy rate naAverage annual occupancy rate
Estimated catchment population 3500000
% total population covered 43%
Table 2. Number of laboratories and number of isolates reported for the period 1999-2003
Year S. pneumoniae
Labs Isolates
S. aureus
Labs Isolates
E. coli
Labs Isolates
Enterococci
Labs Isolates
1999 0 0 0 0 0 0 0 0
2000 9 53 9 156 0 0 0 0
2001 9 63 9 277 9 269 8 74
2002 9 71 10 404 9 417 9 166
2003 18 149 19 773 20 930 18 293
Table 3. Proportion of antibiotic non-susceptible isolates in percent
Pathogen Antimicrobial classes 1999 2000 2001 2002 2003
S. pneumoniae Penicillin R . <1 <1 <1 1
Penicillin I+R . 2 3 1 6
Macrolides I+R . 4 10 10 13
S. aureus Oxacillin/Methicillin R . 5 8 11 14
E. coli Aminopenicillins R . . 35 33 40
Aminoglycosides R . . 1 4 5
Fluoroquinolones R . . 8 10 14
3rd gen. Cephalosporins R . . <1 1 2
E. faecalis Aminopenicillins I+R . . 10 3 <1
Aminoglycosides (high-level resistance) . . 35 17 35
Glycopeptides I+R . . <1 <1 <1
E. faecium Aminopenicillins I+R . . 86 83 87
Aminoglycosides (high-level resistance) . . 13 20 23
Glycopeptides I+R . . 5 8 1
University/tertiary care
General/secondary care
Other
Figure 1. Type of hospitals in 2002
Figure 2. Geographic distribution of laboratories in 2003
AustriaDenominators
Antibiotic resistance in 1999-2003
* Based on labs/hospitals providing denominator data
*
*
*
*
*
*
APPENDIX A 55
Table 4.Details on the origin of invasive isolates in the reporting period
Characteristic S. pneumoniae
n=336
S. aureus
n=1610
E. coli
n=1550
E. faecalis
n=395
E. faecium
n=133
%total %PNSP %total %MRSA %total %FREC %total %VRE %total %VRE
Isolate source
Blood 89 4 100 11 100 12 100 1 100 4
CSF 11 3 0 . 0 . 0 . 0 .
Sex
Male 59 5 60 12 37 12 59 1 57 1
Female 40 2 39 10 62 11 38 0 40 6
Unknown 1 0 1 0 1 29 3 0 3 25
Age (years)
0-4 9 3 3 2 2 5 5 0 5 0
5-19 5 0 3 0 1 9 1 0 2 0
20-64 43 3 38 11 33 12 44 0 56 7
65 and over 44 5 56 13 63 12 49 1 38 0
Unknown 0 . 0 . 0 . 0 . 0 .
Hospital department
ICU 14 6 13 24 7 13 25 2 33 7
Internal Medicine 50 3 43 8 54 11 34 0 28 3
Surgery 2 0 12 17 9 9 12 0 13 0
Other 29 4 29 9 27 14 28 0 26 3
Unknown 4 8 2 3 2 6 2 0 1 0
PNSP at laboratory level MRSA at hospital level
no of hospitals : 31Minimum : 0.01st quartile : 0.0Median : 5.73rd quartile : 10.3Maximum : 62.5
no of labs : 10Minimum : 0.01st quartile : 0.0Median : 5.03rd quartile : 11.1Maximum : 14.3
Figure 4.Proportion (%) MRSA by hospital (1999-2003)
0 25 50 75 100
0/22AT001K
0/7AT001R
0/6AT003B
0/6AT003N
0/11AT005K
0/5AT005R
0/6AT006M
0/7AT006O
0/26AT010B
0/18AT012D
0/11AT012G
1/75AT001S
2/79AT010F
4/99AT001E
1/23AT008T
3/53AT003G
6/105AT006S
1/17AT006N
3/49AT001B
12/187AT007K
1/13AT008S
1/12AT005H
1/10AT005Z
3/29AT005L
5/45AT012W
1/7AT006H
31/176AT002A
50/179AT005I
4/9AT006B
5/9AT012H
5/8AT005C
Figure 3.Proportion (%) PNSP by laboratory (1999-2003)
0 25 50 75 100
0/7AT004
0/29AT005
0/54AT006
0/17AT007
2/75AT001
2/27AT002
1/12AT008
4/36AT010
1/9AT012
2/14AT003
56 APPENDIX A
Table 1. Reference data of 2002
Total
Labs/Hosps reporting to EARSS 102/102
Labs/Hosps providing denom.data 0/0
Number of blood culture sets na
Number of hospital beds na
Average annual occupancy rate naAverage annual occupancy rate
Estimated catchment population na
% total population covered na
Table 2. Number of laboratories and number of isolates reported for the period 1999-2003
Year S. pneumoniae
Labs Isolates
S. aureus
Labs Isolates
E. coli
Labs Isolates
Enterococci
Labs Isolates
1999 92 846 47 442 0 0 0 0
2000 90 909 42 657 0 0 0 0
2001 89 1093 47 941 23 226 19 42
2002 98 1210 48 1092 27 1184 23 205
2003 107 1488 47 1133 24 1326 16 146
Table 3. Proportion of antibiotic non-susceptible isolates in percent
Pathogen Antimicrobial classes 1999 2000 2001 2002 2003
S. pneumoniae Penicillin R 4 5 <1 <1 <1
Penicillin I+R 13 16 13 14 12
Macrolides I+R 31 34 35 34 34
S. aureus Oxacillin/Methicillin R 23 21 23 28 29
E. coli Aminopenicillins R . . 53 47 50
Aminoglycosides R . . 4 6 5
Fluoroquinolones R . . 9 13 12
3rd gen. Cephalosporins R . . 2 3 3
E. faecalis Aminopenicillins I+R . . <1 <1 1
Aminoglycosides (high-level resistance) . . 20 20 17
Glycopeptides I+R . . <1 3 1
E. faecium Aminopenicillins I+R . . 60 56 78
Aminoglycosides (high-level resistance) . . <1 5 <1
Glycopeptides I+R . . <1 <1 <1
University/tertiary care
General/secondary care
Other
Figure 1. Type of hospitals in 2002
Figure 2. Geographic distribution of laboratories in 2003
BelgiumDenominators
Antibiotic resistance in 1999-2003
* Based on labs/hospitals providing denominator data
*
*
*
*
*
*
APPENDIX A 57
Table 4.Details on the origin of invasive isolates in the reporting period
Characteristic S. pneumoniae
n=5546
S. aureus
n=4265
E. coli
n=2362
E. faecalis
n=330
E. faecium
n=54
%total %PNSP %total %MRSA %total %FREC %total %VRE %total %VRE
Isolate source
Blood 94 14 100 26 100 12 100 2 100 0
CSF 6 10 0 . 0 . 0 . 0 .
Sex
Male 56 13 59 26 44 13 62 2 54 0
Female 43 14 40 25 55 11 36 1 43 0
Unknown 1 13 1 21 1 18 2 13 4 0
Age (years)
0-4 19 17 4 8 3 1 4 8 4 0
5-19 6 4 3 6 1 0 1 0 0 .
20-64 30 9 33 20 28 12 28 0 39 0
65 and over 45 16 59 31 68 13 67 3 57 0
Unknown 0 . 2 20 0 . 0 . 0 .
Hospital department
ICU 13 13 16 35 9 9 24 4 33 0
Internal Medicine 34 13 33 19 32 12 38 2 28 0
Surgery 2 16 11 27 6 8 11 0 7 0
Other 27 13 25 29 52 13 25 1 28 0
Unknown 23 14 16 22 1 9 2 0 4 0
PNSP at laboratory level MRSA at hospital level
no of hospitals : 48Minimum : 4.31st quartile : 19.5Median : 28.03rd quartile : 36.4Maximum : 84.6
no of labs : 98Minimum : 0.01st quartile : 9.1Median : 12.13rd quartile : 18.2Maximum : 66.7
Figure 4.Proportion (%) MRSA by hospital (1999-2003)
0 25 50 75 100
2/47BE007X
15/177BE060X
11/128BE002X
2/19BE012X
4/32BE014X
15/114BE115X
32/232BE061X
10/69BE030X
6/41BE057X
20/125BE001X
7/42BE031X
2/11BE004X
39/188BE016X
52/243BE074X
33/150BE024X
8/36BE005X
10/45BE075X
39/171BE077X
12/49BE058X
29/117BE112X
45/172BE008X
9/34BE109X
6/22BE125X
37/134BE006X
72/254BE063X
9/31BE045X
7/24BE003X
26/89BE022X
26/88BE019X
8/27BE114X
43/143BE041X
107/346BE070X
5/16BE040X
13/41BE033X
13/41BE072X
22/61BE029X
123/334BE097X
6/15BE042X
36/86BE032X
44/100BE056X
9/20BE059X
15/30BE017X
4/8BE107X
4/7BE143X
3/5BE068X
17/25BE026X
10/14BE018X
11/13BE065X
Figure 3.Proportion (%) PNSP by laboratory (1999-2003)
0 25 50 75 100
0/5BE0680/7BE1500/5BE156
2/79BE0021/33BE0121/31BE0091/28BE1002/51BE0371/25BE014
1/20BE0211/19BE1163/53BE0042/30BE1143/43BE1033/40BE0548/105BE0018/105BE02414/182BE0708/100BE0308/97BE0614/47BE0053/34BE1184/45BE0137/78BE0931/11BE0819/99BE10413/142BE1158/87BE0064/43BE1105/53BE0232/21BE0446/62BE0576/61BE0906/58BE0519/87BE13911/106BE07710/96BE0634/38BE0174/38BE05918/170BE0563/28BE0207/65BE0221/9BE1291/9BE1526/52BE0495/43BE0263/25BE01010/83BE0584/33BE10214/115BE05512/96BE0321/8BE1459/70BE06041/311BE1087/52BE1016/43BE06411/78BE07420/140BE1129/60BE0198/53BE1097/45BE07218/115BE0973/19BE07115/92BE0088/49BE1057/42BE0037/42BE04110/60BE0483/18BE14136/212BE0926/35BE03512/67BE0758/44BE0314/22BE07631/169BE0915/27BE0439/48BE007
1/5BE12128/133BE016
17/77BE0987/31BE0698/35BE033
9/37BE0842/8BE131
19/69BE0959/31BE029
9/29BE06510/31BE143
3/9BE0182/6BE137
6/15BE0406/15BE0832/5BE1342/5BE135
9/20BE1075/9BE113
3/5BE1464/6BE046
58 APPENDIX A
Table 1. Reference data of 2002
Total
Labs/Hosps reporting to EARSS 22/22
Labs/Hosps providing denom.data 19/18
Number of blood culture sets 15549
Number of hospital beds 9168
Average annual occupancy rate 76%Average annual occupancy rate
Estimated catchment population 7621000
% total population covered 100%
Table 2. Number of laboratories and number of isolates reported for the period 1999-2003
Year S. pneumoniae
Labs Isolates
S. aureus
Labs Isolates
E. coli
Labs Isolates
Enterococci
Labs Isolates
1999 0 0 0 0 0 0 0 0
2000 8 13 16 111 0 0 0 0
2001 8 16 17 103 15 98 11 30
2002 11 25 21 116 20 135 16 42
2003 13 22 20 157 20 158 16 49
Table 3. Proportion of antibiotic non-susceptible isolates in percent
Pathogen Antimicrobial classes 1999 2000 2001 2002 2003
S. pneumoniae Penicillin R . 23 6 8 9
Penicillin I+R . 23 6 8 14
Macrolides I+R . 25 9 9 11
S. aureus Oxacillin/Methicillin R . 37 27 33 31
E. coli Aminopenicillins R . . 48 52 56
Aminoglycosides R . . 16 17 22
Fluoroquinolones R . . 8 14 19
3rd gen. Cephalosporins R . . 7 13 18
E. faecalis Aminopenicillins I+R . . 5 26 7
Aminoglycosides (high-level resistance) . . 30 63 36
Glycopeptides I+R . . <1 4 <1
E. faecium Aminopenicillins I+R . . 50 71 60
Aminoglycosides (high-level resistance) . . 33 83 60
Glycopeptides I+R . . <1 <1 <1
University/tertiary care
General/secondary care
Other
Figure 1.Type of hospitals in 2002
Figure 2. Geographic distribution of laboratories in 2003
BulgariaDenominators
Antibiotic resistance in 1999-2003
* Based on labs/hospitals providing denominator data
*
*
*
*
*
*
APPENDIX A 59
Table 4.Details on the origin of invasive isolates in the reporting period
Characteristic S. pneumoniae
n=76
S. aureus
n=487
E. coli
n=379
E. faecalis
n=97
E. faecium
n=24
%total %PNSP %total %MRSA %total %FREC %total %VRE %total %VRE
Isolate source
Blood 50 8 100 32 98 15 100 1 100 0
CSF 50 16 0 . 2 0 0 . 0 .
Sex
Male 67 16 61 31 47 22 66 2 58 0
Female 32 4 39 33 53 9 34 0 42 0
Unknown 1 0 0 . 0 . 0 . 0 .
Age (years)
0-4 13 40 13 48 12 11 10 0 8 0
5-19 14 18 7 19 4 20 1 0 0 .
20-64 51 3 55 31 48 13 48 2 67 0
65 and over 16 17 22 27 35 17 37 0 13 0
Unknown 5 0 4 40 1 40 3 0 13 0
Hospital department
ICU 12 0 17 51 9 14 21 0 46 0
Internal Medicine 43 12 37 22 45 8 42 0 21 0
Surgery 8 0 15 34 16 24 14 7 13 0
Other 37 18 32 33 30 20 23 0 21 0
Unknown 0 . 0 . 0 . 0 . 0 .
PNSP at laboratory level MRSA at hospital level
no of hospitals : 19Minimum : 0.01st quartile : 8.3Median : 25.93rd quartile : 41.9Maximum : 100
no of labs : 5Minimum : 0.01st quartile : 0.0Median : 12.53rd quartile : 22.2Maximum : 25.0
Figure 4.Proportion (%) MRSA by hospital (1999-2003)
0 25 50 75 100
0/12BG014A
0/8BG018A
0/11BG023A
1/38BG013A
1/12BG004A
1/8BG002A
1/7BG022A
4/19BG021A
2/8BG026A
7/27BG011A
3/10BG024A
15/49BG003A
10/30BG008A
7/19BG007A
18/43BG005A
13/30BG006A
52/116BG001A
6/11BG009A
6/6BG015A
Figure 3.Proportion (%) PNSP by laboratory (1999-2003)
0 25 50 75 100
0/5BG011
0/8BG013
1/8BG003
2/9BG007
3/12BG016
60 APPENDIX A
Table 1. Reference data of 2002
Total
Labs/Hosps reporting to EARSS 15/15
Labs/Hosps providing denom.data 15/15
Number of blood culture sets 34742
Number of hospital beds 8533
Average annual occupancy rate 91%Average annual occupancy rate
Estimated catchment population 3775000
% total population covered 86%
Table 2. Number of laboratories and number of isolates reported for the period 1999-2003
Year S. pneumoniae
Labs Isolates
S. aureus
Labs Isolates
E. coli
Labs Isolates
Enterococci
Labs Isolates
1999 0 0 0 0 0 0 0 0
2000 0 0 0 0 0 0 0 0
2001 10 20 14 149 13 182 7 33
2002 14 90 14 279 15 490 13 96
2003 12 88 14 360 16 570 11 101
Table 3. Proportion of antibiotic non-susceptible isolates in percent
Pathogen Antimicrobial classes 1999 2000 2001 2002 2003
S. pneumoniae Penicillin R . . <1 <1 1
Penicillin I+R . . 15 19 20
Macrolides I+R . . 15 23 18
S. aureus Oxacillin/Methicillin R . . 32 37 37
E. coli Aminopenicillins R . . 51 47 47
Aminoglycosides R . . 6 7 7
Fluoroquinolones R . . 5 5 7
3rd gen. Cephalosporins R . . 2 3 4
E. faecalis Aminopenicillins I+R . . 13 5 4
Aminoglycosides (high-level resistance) . . 50 40 28
Glycopeptides I+R . . 3 <1 <1
E. faecium Aminopenicillins I+R . . 100 56 47
Aminoglycosides (high-level resistance) . . 100 67 41
Glycopeptides I+R . . <1 22 6
University/tertiary care
General/secondary care
Other
Figure 1. Type of hospitals in 2002
Figure 2. Geographic distribution of laboratories in 2003
CroatiaDenominators
Antibiotic resistance in 1999-2003
* Based on labs/hospitals providing denominator data
*
*
*
*
*
*
APPENDIX A 61
Table 4.Details on the origin of invasive isolates in the reporting period
Characteristic S. pneumoniae
n=198
S. aureus
n=788
E. coli
n=1214
E. faecalis
n=179
E. faecium
n=51
%total %PNSP %total %MRSA %total %FREC %total %VRE %total %VRE
Isolate source
Blood 86 19 100 36 100 6 100 1 100 12
CSF 14 18 0 . 0 . 0 . 0 .
Sex
Male 63 21 65 35 40 8 65 0 61 13
Female 37 16 35 37 59 5 35 2 39 10
Unknown 0 . 0 . 1 13 0 . 0 .
Age (years)
0-4 31 23 3 12 7 0 11 0 10 20
5-19 8 27 3 12 2 15 2 0 4 50
20-64 37 16 48 35 34 6 34 0 37 11
65 and over 23 15 46 40 57 7 53 1 49 8
Unknown 1 100 0 . 0 . 0 . 0 .
Hospital department
ICU 16 19 16 64 7 6 17 0 14 0
Internal Medicine 22 16 41 26 41 5 33 0 47 13
Surgery 1 100 12 68 3 5 9 0 4 0
Other 62 20 30 21 49 7 41 1 35 17
Unknown 0 . 0 . 0 . 0 . 0 .
PNSP at laboratory level MRSA at hospital level
no of hospitals : 14Minimum : 0.01st quartile : 14.3Median : 24.53rd quartile : 46.2Maximum : 71.4
no of labs : 8Minimum : 0.01st quartile : 11.1Median : 13.13rd quartile : 23.4Maximum : 25.0
Figure 4.Proportion (%) MRSA by hospital (1999-2003)
0 25 50 75 100
0/22HR014A
2/24HR009A
2/20HR010A
2/14HR018A
2/12HR020A
7/33HR016A
19/82HR002A
17/66HR011A
24/65HR004A
49/119HR007A
18/39HR005A
129/272HR001A
6/11HR013A
5/7HR012A
Figure 3.Proportion (%) PNSP by laboratory (1999-2003)
0 25 50 75 100
0/7HR011
1/9HR005
1/9HR016
1/8HR004
4/29HR007
20/87HR002
5/21HR001
3/12HR014
62 APPENDIX A
Table 1.Reference data of 2002
Total
Labs/Hosps reporting to EARSS 42/95
Labs/Hosps providing denom.data 42/82
Number of blood culture sets 76188
Number of hospital beds 44322
Average annual occupancy rate 78%Average annual occupancy rate
Estimated catchment population 8283000
% total population covered 81%
Table 2.Number of laboratories and number of isolates reported for the period 1999-2003
Year S. pneumoniae
Labs Isolates
S. aureus
Labs Isolates
E. coli
Labs Isolates
Enterococci
Labs Isolates
1999 0 0 0 0 0 0 0 0
2000 26 111 31 515 0 0 0 0
2001 32 154 39 1074 36 1176 34 461
2002 34 144 41 1168 40 1587 39 587
2003 32 204 45 1387 43 1766 44 630
Table 3.Proportion of antibiotic non-susceptible isolates in percent
Pathogen Antimicrobial classes 1999 2000 2001 2002 2003
S. pneumoniae Penicillin R . <1 <1 <1 <1
Penicillin I+R . 4 7 8 2
Macrolides I+R . 1 2 4 2
S. aureus Oxacillin/Methicillin R . 4 6 6 6
E. coli Aminopenicillins R . . 42 45 45
Aminoglycosides R . . 6 6 5
Fluoroquinolones R . . 8 10 13
3rd gen. Cephalosporins R . . 2 1 1
E. faecalis Aminopenicillins I+R . . 3 2 4
Aminoglycosides (high-level resistance) . . 38 39 44
Glycopeptides I+R . . 2 <1 <1
E. faecium Aminopenicillins I+R . . 67 73 80
Aminoglycosides (high-level resistance) . . 33 35 48
Glycopeptides I+R . . 2 9 3
University/tertiary care
General/secondary care
Other
Figure 1.Type of hospitals in 2002
Figure 2.Geographic distribution of laboratories in 2003
Czech RepublicDenominators
Antibiotic resistance in 1999-2003
* Based on labs/hospitals providing denominator data
*
*
*
*
*
*
APPENDIX A 63
Table 4.Details on the origin of invasive isolates in the reporting period
Characteristic S. pneumoniae
n=613
S. aureus
n=4144
E. coli
n=4524
E. faecalis
n=1428
E. faecium
n=238
%total %PNSP %total %MRSA %total %FREC %total %VRE %total %VRE
Isolate source
Blood 72 6 100 6 100 11 100 1 100 5
CSF 28 4 0 . 0 . 0 . 0 .
Sex
Male 62 5 59 6 42 12 62 1 59 4
Female 38 6 41 5 58 10 38 0 41 5
Unknown 0 . 0 . 0 . 0 . 0 .
Age (years)
0-4 12 10 4 4 5 3 6 0 5 0
5-19 8 0 3 5 1 6 1 0 3 0
20-64 50 5 45 6 34 12 46 1 49 6
65 and over 30 5 47 6 61 11 47 1 44 4
Unknown 0 . 0 . 0 . 0 . 0 .
Hospital department
ICU 18 4 15 10 10 11 28 0 30 3
Internal Medicine 40 6 49 4 54 11 32 1 31 3
Surgery 2 15 13 8 10 11 15 1 9 5
Other 39 4 22 5 25 10 25 1 29 7
Unknown 0 . 0 . 0 . 0 . 0 .
PNSP at laboratory level MRSA at hospital level
no of hospitals : 72Minimum : 0.01st quartile : 0.0Median : 2.03rd quartile : 5.8Maximum : 40.0
no of labs : 30Minimum : 0.01st quartile : 0.0Median : 4.03rd quartile : 9.1Maximum : 25.0
Figure 4.Proportion (%) MRSA by hospital (1999-2003)
0 25 50 75 100
0/7CZ004B0/11CZ007D0/7CZ007E0/24CZ009B0/40CZ011A0/19CZ012B0/10CZ012C0/15CZ012D0/6CZ014B0/14CZ015B0/21CZ017D0/14CZ022B0/111CZ023A0/32CZ025A0/5CZ027B0/35CZ028A0/6CZ028B0/46CZ029A0/8CZ031E0/10CZ031F0/6CZ031J0/6CZ031N0/15CZ031P0/5CZ031S0/7CZ031Y0/38CZ038A0/20CZ039A0/6CZ039C0/16CZ040A0/6CZ040B0/6CZ040C1/120CZ002A1/86CZ027A3/233CZ009A1/67CZ026A2/105CZ015A1/48CZ013A2/93CZ004A1/44CZ037A1/42CZ030A2/80CZ012A1/35CZ036A2/58CZ019A5/142CZ016A11/299CZ006A1/27CZ017C2/51CZ022A6/147CZ021A2/45CZ034A1/22CZ019B1/21CZ008A2/42CZ032A4/81CZ007A2/40CZ014A
14/211CZ017A9/127CZ031A9/123CZ005A1/13CZ031C13/164CZ020A1/12CZ031K2/23CZ041A9/103CZ024A
9/91CZ035A9/72CZ017B
52/348CZ018A14/90CZ003A
4/24CZ042A21/100CZ033A
3/12CZ039B4/15CZ031V
5/14CZ043A2/5CZ031M
Figure 3.Proportion (%) PNSP by laboratory (1999-2003)
0 25 50 75 100
0/10CZ008
0/10CZ013
0/9CZ014
0/60CZ016
0/15CZ019
0/10CZ022
0/22CZ024
0/33CZ027
0/7CZ029
0/12CZ030
0/8CZ032
0/15CZ033
0/8CZ036
1/28CZ015
1/26CZ002
3/71CZ006
1/21CZ031
1/19CZ004
1/18CZ023
3/44CZ009
2/26CZ012
2/24CZ007
1/11CZ005
1/11CZ026
4/30CZ017
1/7CZ021
3/17CZ003
1/5CZ020
1/5CZ037
2/8CZ025
64 APPENDIX A
Table 1. Reference data of 2002
Total
Labs/Hosps reporting to EARSS 5/35
Labs/Hosps providing denom.data 0/35
Number of blood culture sets na
Number of hospital beds na
Average annual occupancy rate naAverage annual occupancy rate
Estimated catchment population 2490000
% total population covered 46%
Table 2. Number of laboratories and number of isolates reported for the period 1999-2003
Year S. pneumoniae
Labs Isolates
S. aureus
Labs Isolates
E. coli
Labs Isolates
Enterococci
Labs Isolates
1999 0 0 5 718 0 0 0 0
2000 5 410 4 501 0 0 0 0
2001 5 506 4 520 0 0 0 0
2002 5 366 5 752 0 0 0 0
2003 5 606 5 671 0 0 0 0
Table 3. Proportion of antibiotic non-susceptible isolates in percent
Pathogen Antimicrobial classes 1999 2000 2001 2002 2003
S. pneumoniae Penicillin R . <1 <1 <1 <1
Penicillin I+R . 4 3 4 3
Macrolides I+R . 5 5 5 5
S. aureus Oxacillin/Methicillin R < 1 <1 <1 <1 <1
E. coli Aminopenicillins R . . . . .
Aminoglycosides R . . . . .
Fluoroquinolones R . . . . .
3rd gen. Cephalosporins R . . . . .
E. faecalis Aminopenicillins I+R . . . . .
Aminoglycosides (high-level resistance) . . . . .
Glycopeptides I+R . . . . .
E. faecium Aminopenicillins I+R . . . . .
Aminoglycosides (high-level resistance) . . . . .
Glycopeptides I+R . . . . .
University/tertiary care
General/secondary care
Other
Figure 1. Type of hospitals in 2002
Figure 2. Geographic distribution of laboratories in 2003
DenmarkDenominators
Antibiotic resistance in 1999-2003
* Based on labs/hospitals providing denominator data
*
*
*
*
*
*
APPENDIX A 65
Table 4.Details on the origin of invasive isolates in the reporting period
Characteristic S. pneumoniae
n=1888
S. aureus
n=3162
E. coli
n=0
E. faecalis
n=0
E. faecium
n=0
%total %PNSP %total %MRSA %total %FREC %total %VRE %total %VRE
Isolate source
Blood 91 3 100 1 . . . . . .
CSF 9 2 0 . . . . . . .
Sex
Male 49 3 58 1 . . . . . .
Female 51 3 39 0 . . . . . .
Unknown 0 . 2 1 . . . . . .
Age (years)
0-4 8 5 1 0 . . . . . .
5-19 2 5 3 1 . . . . . .
20-64 39 3 41 1 . . . . . .
65 and over 51 3 54 1 . . . . . .
Unknown 0 . 0 . . . . . . .
Hospital department
ICU 0 . 5 0 . . . . . .
Internal Medicine 0 . 49 1 . . . . . .
Surgery 0 . 18 0 . . . . . .
Other 0 . 16 1 . . . . . .
Unknown 100 3 11 1 . . . . . .
PNSP at laboratory level MRSA at hospital level
no of hospitals : 28Minimum : 0.01st quartile : 0.0Median : 0.03rd quartile : 0.4Maximum : 1.7
no of labs : 5Minimum : 1.91st quartile : 2.5Median : 3.93rd quartile : 3.9Maximum : 3.9
Figure 4.Proportion (%) MRSA by hospital (1999-2003)
0 25 50 75 100
0/82DK005B
0/59DK008A
0/85DK009A
0/16DK009C
0/30DK009D
0/41DK009F
0/7DK009G
0/47DK014A
0/149DK014B
0/114DK014C
0/22DK014E
0/12DK014F
0/16DK014G
0/122DK014N
0/114DK016B
0/73DK016C
0/37DK016D
0/29DK016F
0/41DK016G
0/15DK016H
1/462DK016A
1/152DK005A
2/231DK002A
3/339DK002B
6/525DK009B
1/82DK014D
2/127DK002E
2/119DK002F
Figure 3.Proportion (%) PNSP by laboratory (1999-2003)
0 25 50 75 100
7/370DK016
12/487DK014
17/439DK002
8/206DK005
15/386DK009
66 APPENDIX A
Table 1.Reference data of 2002
Total
Labs/Hosps reporting to EARSS 8/12
Labs/Hosps providing denom.data 7/7
Number of blood culture sets 4217
Number of hospital beds 3021
Average annual occupancy rate 75%Average annual occupancy rate
Estimated catchment population 1416000
% total population covered 100%
Table 2.Number of laboratories and number of isolates reported for the period 1999-2003
Year S. pneumoniae
Labs Isolates
S. aureus
Labs Isolates
E. coli
Labs Isolates
Enterococci
Labs Isolates
1999 0 0 0 0 0 0 0 0
2000 0 0 0 0 0 0 0 0
2001 5 20 6 79 4 52 4 21
2002 5 21 8 81 6 67 3 13
2003 8 26 9 98 9 98 6 27
Table 3.Proportion of antibiotic non-susceptible isolates in percent
Pathogen Antimicrobial classes 1999 2000 2001 2002 2003
S. pneumoniae Penicillin R . . <1 <1 <1
Penicillin I+R . . <1 <1 <1
Macrolides I+R . . 5 <1 10
S. aureus Oxacillin/Methicillin R . . 5 1 4
E. coli Aminopenicillins R . . 43 42 42
Aminoglycosides R . . 8 10 3
Fluoroquinolones R . . <1 5 5
3rd gen. Cephalosporins R . . 6 2 1
E. faecalis Aminopenicillins I+R . . 8 10 4
Aminoglycosides (high-level resistance) . . <1 50 22
Glycopeptides I+R . . <1 <1 5
E. faecium Aminopenicillins I+R . . 63 33 75
Aminoglycosides (high-level resistance) . . 63 67 50
Glycopeptides I+R . . <1 <1 <1
University/tertiary care
General/secondary care
Other
Figure 1.Type of hospitals in 2002
Figure 2.Geographic distribution of laboratories in 2003
EstoniaDenominators
Antibiotic resistance in 1999-2003
* Based on labs/hospitals providing denominator data
*
*
*
*
*
*
APPENDIX A 67
Table 4.Details on the origin of invasive isolates in the reporting period
Characteristic S. pneumoniae
n=67
S. aureus
n=258
E. coli
n=193
E. faecalis
n=45
E. faecium
n=15
%total %PNSP %total %MRSA %total %FREC %total %VRE %total %VRE
Isolate source
Blood 48 0 100 3 99 4 100 2 100 0
CSF 52 0 0 . 1 0 0 . 0 .
Sex
Male 69 0 56 6 34 5 49 5 73 0
Female 28 0 38 1 64 3 44 0 27 0
Unknown 3 0 6 0 2 0 7 0 0 .
Age (years)
0-4 6 0 10 11 5 0 29 8 13 0
5-19 9 0 7 6 2 0 0 . 7 0
20-64 34 0 35 1 33 2 16 0 27 0
65 and over 4 0 11 4 31 5 24 0 40 0
Unknown 46 0 37 3 29 5 31 0 13 0
Hospital department
ICU 36 0 18 2 20 8 18 0 33 0
Internal Medicine 13 0 29 1 27 2 9 0 7 0
Surgery 3 0 16 5 10 5 16 0 13 0
Other 48 0 37 5 41 3 58 4 47 0
Unknown 0 . 0 . 2 0 0 . 0 .
PNSP at laboratory level MRSA at hospital level
no of hospitals : 7Minimum : 0.01st quartile : 0.0Median : 1.13rd quartile : 2.7Maximum : 18.2
no of labs : 5Minimum : 0.01st quartile : 0.0Median : 0.03rd quartile : 0.0Maximum : 0.0
Figure 4.Proportion (%) MRSA by hospital (1999-2003)
0 25 50 75 100
0/11EE003R
0/9EE004P
0/9EE005P
1/88EE001A
1/43EE002M
1/37EE006K
4/22EE002L
Figure 3.Proportion (%) PNSP by laboratory (1999-2003)
0 25 50 75 100
0/22EE001
0/22EE002
0/5EE003
0/8EE006
0/5EE009
68 APPENDIX A
Table 1. Reference data of 2002
Total
Labs/Hosps reporting to EARSS 16/16
Labs/Hosps providing denom.data 13/12
Number of blood culture sets 121484
Number of hospital beds 8880
Average annual occupancy rate 86%Average annual occupancy rate
Estimated catchment population 4242000
% total population covered 82%
Table 2. Number of laboratories and number of isolates reported for the period 1999-2003
Year S. pneumoniae
Labs Isolates
S. aureus
Labs Isolates
E. coli
Labs Isolates
Enterococci
Labs Isolates
1999 14 242 13 316 0 0 0 0
2000 9 176 12 362 0 0 0 0
2001 13 425 13 606 14 1284 13 274
2002 15 453 15 721 15 1330 14 278
2003 16 490 16 727 15 1450 15 266
Table 3. Proportion of antibiotic non-susceptible isolates in percent
Pathogen Antimicrobial classes 1999 2000 2001 2002 2003
S. pneumoniae Penicillin R < 1 <1 1 2 2
Penicillin I+R 4 5 9 6 10
Macrolides I+R 6 8 12 14 20
S. aureus Oxacillin/Methicillin R < 1 1 <1 <1 1
E. coli Aminopenicillins R . . 33 30 33
Aminoglycosides R . . <1 <1 1
Fluoroquinolones R . . 5 6 5
3rd gen. Cephalosporins R . . <1 <1 <1
E. faecalis Aminopenicillins I+R . . 1 2 <1
Aminoglycosides (high-level resistance) . . 23 13 39
Glycopeptides I+R . . <1 <1 <1
E. faecium Aminopenicillins I+R . . 66 80 79
Aminoglycosides (high-level resistance) . . <1 <1 4
Glycopeptides I+R . . <1 1 <1
University/tertiary care
General/secondary care
Other
Figure 1. Type of hospitals in 2002
Figure 2. Geographic distribution of laboratories in 2003
FinlandDenominators
Antibiotic resistance in 1999-2003
* Based on labs/hospitals providing denominator data
*
*
*
*
*
*
APPENDIX A 69
Table 4.Details on the origin of invasive isolates in the reporting period
Characteristic S. pneumoniae
n=1786
S. aureus
n=2732
E. coli
n=3984
E. faecalis
n=539
E. faecium
n=278
%total %PNSP %total %MRSA %total %FREC %total %VRE %total %VRE
Isolate source
Blood 95 8 100 1 100 6 100 0 100 0
CSF 5 6 0 . 0 . 0 . 0 .
Sex
Male 56 6 61 1 35 5 63 0 61 0
Female 44 10 39 1 65 6 37 1 39 1
Unknown 0 . 0 . 0 . 0 . 0 .
Age (years)
0-4 13 12 3 0 3 0 6 0 2 0
5-19 5 6 6 1 1 4 1 0 2 0
20-64 50 6 44 1 31 3 33 1 45 0
65 and over 32 8 46 1 65 7 60 0 51 1
Unknown 0 . 1 10 0 . 0 . 0 .
Hospital department
ICU 2 9 2 0 0 . 0 . 2 0
Internal Medicine 15 5 17 1 10 6 13 3 17 0
Surgery 4 4 11 1 10 8 11 0 8 0
Other 40 7 30 1 34 5 32 0 31 0
Unknown 38 9 40 1 46 6 44 0 42 1
PNSP at laboratory level MRSA at hospital level
no of hospitals : 22Minimum : 0.01st quartile : 0.0Median : 0.83rd quartile : 1.7Maximum : 4.5
no of labs : 17Minimum : 0.01st quartile : 5.8Median : 6.53rd quartile : 9.1Maximum : 16.3
Figure 4.Proportion (%) MRSA by hospital (1999-2003)
0 25 50 75 100
0/129FI003A
0/63FI004A
0/55FI008A
0/54FI009A
0/161FI00HX
0/63FI010X
0/37FI015X
0/52FI017X
1/323FI002A
1/143FI00HA
1/136FI001X
1/123FI00CX
1/105FI012A
2/197FI005X
1/66FI00EX
7/455FI002X
1/60FI009X
1/57FI010A
2/92FI011A
3/121FI00CA
3/79FI014A
2/44FI015A
Figure 3.Proportion (%) PNSP by laboratory (1999-2003)
0 25 50 75 100
0/38FI008
0/9FI00L
1/78FI012
5/125FI00C
8/138FI001
11/178FI00H
4/64FI017
7/111FI005
6/93FI003
3/40FI00E
5/56FI015
6/67FI009
2/22FI004
52/560FI002
6/64FI011
6/52FI014
7/43FI010
70 APPENDIX A
Table 1. Reference data of 2002
Total
Labs/Hosps reporting to EARSS 21/21
Labs/Hosps providing denom.data 21/21
Number of blood culture sets 242938
Number of hospital beds 18804
Average annual occupancy rate 84%Average annual occupancy rate
Estimated catchment population na
% total population covered na
Table 2. Number of laboratories and number of isolates reported for the period 1999-2003
Year S. pneumoniae
Labs Isolates
S. aureus
Labs Isolates
E. coli
Labs Isolates
Enterococci
Labs Isolates
1999 0 0 0 0 0 0 0 0
2000 0 0 0 0 0 0 0 0
2001 329 1337 21 1714 0 0 0 0
2002 296 1132 21 1663 21 2495 21 467
2003 298 547 21 1708 21 2267 21 483
Table 3. Proportion of antibiotic non-susceptible isolates in percent
Pathogen Antimicrobial classes 1999 2000 2001 2002 2003
S. pneumoniae Penicillin R . . 11 8 8
Penicillin I+R . . 47 48 41
Macrolides I+R . . 49 53 48
S. aureus Oxacillin/Methicillin R . . 33 33 29
E. coli Aminopenicillins R . . . 52 48
Aminoglycosides R . . . 4 5
Fluoroquinolones R . . . 8 9
3rd gen. Cephalosporins R . . . <1 <1
E. faecalis Aminopenicillins I+R . . . 5 3
Aminoglycosides (high-level resistance) . . . 15 16
Glycopeptides I+R . . . <1 1
E. faecium Aminopenicillins I+R . . . 34 30
Aminoglycosides (high-level resistance) . . . 10 23
Glycopeptides I+R . . . 2 <1
University/tertiary care
General/secondary care
Other
Figure 1. Type of hospitals in 2002
Figure 2. Geographic distribution of laboratories in 2003
The Observatoires Regionaux du Pneumocoque (ORP) and the NRCinvolved in invasive pneumococcal infections survey are nationwidedistributed.
FranceDenominators
Antibiotic resistance in 1999-2003
* Based on labs/hospitals providing denominator data
*
*
*
*
*
*
*
**
* aggregated data ** Two first quarters of 2003
*
*
*
* Two first quarters of 2003
APPENDIX A 71
Table 4.Details on the origin of invasive isolates in the reporting period
Characteristic S. pneumoniae
n=2469
S. aureus
n=5085
E. coli
n=4754
E. faecalis
n=671
E. faecium
n=246
%total %PNSP %total %MRSA %total %FREC %total %VRE %total %VRE
Isolate source
Blood 77 48 100 32 100 9 100 1 100 1
CSF 23 46 0 . 0 . 0 . 0 .
Sex
Male . . 59 31 40 10 61 1 56 0
Female . . 32 33 48 7 30 0 39 2
Unknown . . 10 35 12 10 9 3 5 0
Age (years)
0-4 29 60 3 10 2 6 4 0 4 0
5-19 6 26 3 9 1 5 1 0 2 0
20-64 30 37 44 26 41 9 42 0 47 2
65 and over 34 49 50 39 55 9 52 1 46 0
Unknown 1 90 0 . 0 . 0 . 0 .
Hospital department
ICU . . 23 37 13 9 29 0 20 0
Internal Medicine . . 31 34 31 9 19 2 22 0
Surgery . . 20 32 14 11 24 1 26 2
Other . . 26 25 42 8 28 2 32 1
Unknown . . 0 . 0 . 0 . 1 0
PNSP at laboratory level MRSA at hospital level
**
** for 2001 and 2002
no of hospitals : 21Minimum : 21.91st quartile : 28.2Median : 30.63rd quartile : 35.0Maximum : 48.1
Figure 4.Proportion (%) MRSA by hospital (1999-2003)
0 25 50 75 100
35/160FR164A
11/49FR095A
152/606FR248A
33/125FR126A
92/329FR010A
121/429FR226A
11/38FR208A
43/147FR362A
108/355FR238A
79/259FR165A
67/219FR121A
50/159FR194A
68/206FR105A
35/104FR252A
167/496FR263A
143/409FR138A
36/95FR211A
154/381FR246A
34/83FR120A
41/97FR037A
25/52FR046A
Figure 3.Proportion (%) PNSP by laboratory (1999-2003)
0 25 50 75 100
Data per laboratory were not transmitted
72 APPENDIX A
Table 1. Reference data of 2002
Total
Labs/Hosps reporting to EARSS 19/19
Labs/Hosps providing denom.data 2/0
Number of blood culture sets 10317
Number of hospital beds na
Average annual occupancy rate naAverage annual occupancy rate
Estimated catchment population na
% total population covered na
Table 2. Number of laboratories and number of isolates reported for the period 1999-2003
Year S. pneumoniae
Labs Isolates
S. aureus
Labs Isolates
E. coli
Labs Isolates
Enterococci
Labs Isolates
1999 23 417 25 1239 0 0 0 0
2000 18 204 19 890 0 0 0 0
2001 21 211 22 1220 21 1269 20 295
2002 16 232 18 1039 16 1026 13 282
2003 9 55 12 225 12 221 8 84
Table 3. Proportion of antibiotic non-susceptible isolates in percent
Pathogen Antimicrobial classes 1999 2000 2001 2002 2003
S. pneumoniae Penicillin R < 1 <1 1 <1 <1
Penicillin I+R 2 2 4 1 <1
Macrolides I+R 7 10 17 14 13
S. aureus Oxacillin/Methicillin R 8 12 16 19 18
E. coli Aminopenicillins R . . 46 50 47
Aminoglycosides R . . 5 5 5
Fluoroquinolones R . . 11 15 15
3rd gen. Cephalosporins R . . <1 <1 <1
E. faecalis Aminopenicillins I+R . . 8 9 7
Aminoglycosides (high-level resistance) . . 31 42 38
Glycopeptides I+R . . <1 1 <1
E. faecium Aminopenicillins I+R . . 79 79 69
Aminoglycosides (high-level resistance) . . 43 68 38
Glycopeptides I+R . . 1 6 <1
University/tertiary care
General/secondary care
Other
Figure 1. Type of hospitals in 2002
Figure 2. Geographic distribution of laboratories in 2003
GermanyDenominators
Antibiotic resistance in 1999-2003
* Based on labs/hospitals providing denominator data
*
*
*
*
*
*
APPENDIX A 73
Table 4.Details on the origin of invasive isolates in the reporting period
Characteristic S. pneumoniae
n=1119
S. aureus
n=4613
E. coli
n=2470
E. faecalis
n=479
E. faecium
n=164
%total %PNSP %total %MRSA %total %FREC %total %VRE %total %VRE
Isolate source
Blood 93 2 100 14 100 13 100 1 100 3
CSF 7 3 0 . 0 . 0 . 0 .
Sex
Male 50 3 52 16 37 14 60 1 58 3
Female 38 2 35 13 50 13 33 1 40 3
Unknown 13 1 13 7 13 12 7 0 2 0
Age (years)
0-4 9 4 3 7 2 0 2 0 4 0
5-19 3 7 2 8 1 13 0 . 1 0
20-64 43 3 39 13 27 14 38 2 43 1
65 and over 44 1 55 15 70 13 59 0 52 5
Unknown 1 0 1 15 0 . 1 0 1 0
Hospital department
ICU 17 4 19 26 12 13 26 0 30 6
Internal Medicine 48 1 44 10 53 11 38 1 31 2
Surgery 2 0 9 12 6 14 8 3 10 0
Other 22 2 18 12 22 17 23 1 26 0
Unknown 12 1 10 10 8 15 5 0 3 20
PNSP at laboratory level MRSA at hospital level
no of hospitals : 24Minimum : 0.01st quartile : 4.9Median : 8.93rd quartile : 18.5Maximum : 37.5
no of labs : 22Minimum : 0.01st quartile : 0.0Median : 0.33rd quartile : 3.4Maximum : 16.7
Figure 4.Proportion (%) MRSA by hospital (1999-2003)
0 25 50 75 100
0/85DE0703X
0/56DE0802X
0/25DE1401X
4/160DE0701X
3/67DE1402X
2/44DE0702X
10/190DE0902X
13/239DE1301X
2/36DE0206X
17/276DE1203X
8/123DE0501X
63/716DE0803X
13/143DE0102X
24/205DE0905X
11/87DE0202X
13/82DE0901X
5/31DE0105X
56/329DE0306X
154/772DE0302X
31/145DE0301X
20/91DE0101X
160/552DE0204X
7/22DE0801X
24/64DE0303X
Figure 3.Proportion (%) PNSP by laboratory (1999-2003)
0 25 50 75 100
0/93DE0102
0/6DE0103
0/13DE0206
0/12DE0301
0/154DE0302
0/47DE0306
0/47DE0501
0/14DE0702
0/14DE0703
0/26DE0901
0/6DE1402
1/173DE0803
1/85DE1301
1/43DE0303
2/84DE0902
1/41DE0905
4/116DE0204
1/26DE0802
1/21DE0701
2/33DE0101
4/26DE1203
3/18DE0801
74 APPENDIX A
Table 1. Reference data of 2002
Total
Labs/Hosps reporting to EARSS 36/36
Labs/Hosps providing denom.data 0/0
Number of blood culture sets na
Number of hospital beds na
Average annual occupancy rate naAverage annual occupancy rate
Estimated catchment population na
% total population covered na
Table 2. Number of laboratories and number of isolates reported for the period 1999-2003
Year S. pneumoniae
Labs Isolates
S. aureus
Labs Isolates
E. coli
Labs Isolates
Enterococci
Labs Isolates
1999 0 0 19 192 0 0 0 0
2000 0 0 15 356 0 0 0 0
2001 0 0 25 358 26 619 25 304
2002 0 0 33 368 35 588 28 293
2003 0 0 30 321 30 507 30 320
Table 3. Proportion of antibiotic non-susceptible isolates in percent
Pathogen Antimicrobial classes 1999 2000 2001 2002 2003
S. pneumoniae Penicillin R . . . . .
Penicillin I+R . . . . .
Macrolides I+R . . . . .
S. aureus Oxacillin/Methicillin R 31 51 40 44 51
E. coli Aminopenicillins R . . 46 46 43
Aminoglycosides R . . 5 7 7
Fluoroquinolones R . . 8 13 10
3rd gen. Cephalosporins R . . 5 6 5
E. faecalis Aminopenicillins I+R . . 8 4 3
Aminoglycosides (high-level resistance) . . 57 60 57
Glycopeptides I+R . . 10 15 9
E. faecium Aminopenicillins I+R . . 86 75 88
Aminoglycosides (high-level resistance) . . 45 52 38
Glycopeptides I+R . . 18 19 23
University/tertiary care
General/secondary care
Other
Figure 1. Type of hospitals in 2002
Figure 2. Geographic distribution of laboratories in 2003
GreeceDenominators
Antibiotic resistance in 1999-2003
* Based on labs/hospitals providing denominator data
*
*
*
*
*
*
APPENDIX A 75
Table 4.Details on the origin of invasive isolates in the reporting period
Characteristic S. pneumoniae
n=0
S. aureus
n=1595
E. coli
n=1662
E. faecalis
n=633
E. faecium
n=254
%total %PNSP %total %MRSA %total %FREC %total %VRE %total %VRE
Isolate source
Blood . . 100 44 100 11 100 11 100 20
CSF . . 0 . 0 . 0 . 0 .
Sex
Male . . 16 39 12 11 15 11 18 27
Female . . 11 42 19 7 13 12 11 33
Unknown . . 73 46 69 11 72 11 72 16
Age (years)
0-4 . . 0 . 0 . 0 . 0 .
5-19 . . 1 0 0 . 0 . 0 .
20-64 . . 1 42 2 13 1 0 1 33
65 and over . . 1 48 2 17 3 5 2 33
Unknown . . 97 45 96 10 96 12 96 20
Hospital department
ICU . . 17 70 3 16 42 18 39 23
Internal Medicine . . 59 37 78 10 39 4 44 15
Surgery . . 11 55 10 14 12 13 8 19
Other . . 5 21 2 4 1 0 1 50
Unknown . . 7 45 7 16 5 7 8 30
PNSP at laboratory level MRSA at hospital level
no of hospitals : 24Minimum : 0.01st quartile : 29.2Median : 38.23rd quartile : 49.5Maximum : 71.4
Figure 4.Proportion (%) MRSA by hospital (1999-2003)
0 25 50 75 100
0/9GR026A
1/13GR042A
1/7GR024A
2/10GR043A
9/39GR044A
6/24GR013A
12/36GR015A
21/62GR028A
13/36GR007A
4/11GR032A
16/43GR027A
24/63GR030A
23/60GR047A
36/91GR033A
20/45GR001A
16/35GR035A
7/15GR018A
26/53GR012A
14/28GR039A
147/277GR040A
68/115GR014A
7/10GR004A
33/47GR005A
5/7GR046A
Figure 3.Proportion (%) PNSP by laboratory (1999-2003)
0 25 50 75 100
Not enough data per laboratory to provide a graph
76 APPENDIX A
Table 1. Reference data of 2002
Total
Labs/Hosps reporting to EARSS 26/69
Labs/Hosps providing denom.data 26/56
Number of blood culture sets 19656
Number of hospital beds 34569
Average annual occupancy rate 78%Average annual occupancy rate
Estimated catchment population 9312000
% total population covered 92%
Table 2. Number of laboratories and number of isolates reported for the period 1999-2003
Year S. pneumoniae
Labs Isolates
S. aureus
Labs Isolates
E. coli
Labs Isolates
Enterococci
Labs Isolates
1999 0 0 0 0 0 0 0 0
2000 0 0 0 0 0 0 0 0
2001 14 36 18 301 18 264 17 121
2002 17 61 24 413 24 354 23 169
2003 20 134 27 858 27 842 25 279
Table 3. Proportion of antibiotic non-susceptible isolates in percent
Pathogen Antimicrobial classes 1999 2000 2001 2002 2003
S. pneumoniae Penicillin R . . 8 3 3
Penicillin I+R . . 22 23 24
Macrolides I+R . . 19 21 25
S. aureus Oxacillin/Methicillin R . . 5 9 15
E. coli Aminopenicillins R . . 47 45 49
Aminoglycosides R . . 4 6 8
Fluoroquinolones R . . 5 10 15
3rd gen. Cephalosporins R . . <1 2 <1
E. faecalis Aminopenicillins I+R . . 5 2 <1
Aminoglycosides (high-level resistance) . . . 100 87
Glycopeptides I+R . . <1 3 <1
E. faecium Aminopenicillins I+R . . 100 89 91
Aminoglycosides (high-level resistance) . . . 100 96
Glycopeptides I+R . . <1 <1 <1
University/tertiary care
General/secondary care
Other
Figure 1. Type of hospitals in 2002
Figure 2. Geographic distribution of laboratories in 2003
HungaryDenominators
Antibiotic resistance in 1999-2003
* Based on labs/hospitals providing denominator data
*
*
*
*
*
*
APPENDIX A 77
Table 4.Details on the origin of invasive isolates in the reporting period
Characteristic S. pneumoniae
n=231
S. aureus
n=1572
E. coli
n=1397
E. faecalis
n=481
E. faecium
n=77
%total %PNSP %total %MRSA %total %FREC %total %VRE %total %VRE
Isolate source
Blood 67 26 100 11 98 12 100 1 100 0
CSF 33 18 0 . 2 0 0 . 0 .
Sex
Male 66 24 61 12 53 14 56 1 53 0
Female 33 24 37 11 46 10 44 2 47 0
Unknown 1 0 1 6 1 0 1 0 0 .
Age (years)
0-4 13 39 2 9 3 0 2 0 9 0
5-19 5 8 2 11 1 12 2 0 1 0
20-64 55 21 50 11 41 12 50 1 42 0
65 and over 27 24 45 12 55 13 45 2 48 0
Unknown 0 . 0 . 0 . 0 . 0 .
Hospital department
ICU 17 15 15 29 10 12 25 0 35 0
Internal Medicine 29 25 37 6 42 11 28 2 14 0
Surgery 2 20 12 17 7 12 9 2 18 0
Other 41 23 19 8 29 14 22 0 27 0
Unknown 11 32 17 8 12 11 16 3 5 0
PNSP at laboratory level MRSA at hospital level
no of hospitals : 40Minimum : 0.01st quartile : 1.0Median : 9.83rd quartile : 16.7Maximum : 36.8
no of labs : 15Minimum : 11.81st quartile : 16.7Median : 25.03rd quartile : 28.6Maximum : 75.0
Figure 4.Proportion (%) MRSA by hospital (1999-2003)
0 25 50 75 100
0/18HU002H
0/6HU004G
0/13HU005W
0/8HU005Y
0/5HU006C
0/8HU007C
0/14HU019D
0/19HU020L
0/9HU023E
0/24HU024A
1/49HU027A
4/138HU019A
3/86HU021A
2/54HU016A
1/21HU007B
2/41HU009B
4/65HU020A
1/11HU016D
3/31HU006B
6/62HU014A
1/10HU004Y
2/18HU015A
1/9HU020C
5/44HU017A
3/25HU001U
7/56HU026A
2/15HU021C
7/51HU005A
5/31HU023B
2/12HU006A
2/12HU008C
9/52HU023L
2/10HU002X
20/96HU009A
5/24HU023C
25/105HU004Z
10/42HU013A
5/21HU023D
4/15HU002R
7/19HU003A
Figure 3.Proportion (%) PNSP by laboratory (1999-2003)
0 25 50 75 100
2/17HU020
1/7HU005
2/13HU026
5/30HU019
3/17HU009
2/11HU027
2/10HU007
2/8HU016
3/12HU025
2/8HU028
3/11HU021
2/7HU014
6/20HU006
4/11HU002
6/8HU013
78 APPENDIX A
Table 1. Reference data of 2002
Total
Labs/Hosps reporting to EARSS 2/2
Labs/Hosps providing denom.data 2/2
Number of blood culture sets 8647
Number of hospital beds 1139
Average annual occupancy rate 92%Average annual occupancy rate
Estimated catchment population 279000
% total population covered 100%
Table 2. Number of laboratories and number of isolates reported for the period 1999-2003
Year S. pneumoniae
Labs Isolates
S. aureus
Labs Isolates
E. coli
Labs Isolates
Enterococci
Labs Isolates
1999 1 48 1 32 0 0 0 0
2000 1 36 1 40 0 0 0 0
2001 2 48 2 63 2 86 2 18
2002 2 43 2 60 2 83 2 25
2003 2 35 2 64 2 100 2 22
Table 3. Proportion of antibiotic non-susceptible isolates in percent
Pathogen Antimicrobial classes 1999 2000 2001 2002 2003
S. pneumoniae Penicillin R < 1 <1 <1 2 <1
Penicillin I+R 2 8 6 5 9
Macrolides I+R 3 11 8 5 20
S. aureus Oxacillin/Methicillin R < 1 3 <1 <1 <1
E. coli Aminopenicillins R . . 42 33 42
Aminoglycosides R . . 4 1 2
Fluoroquinolones R . . 4 3 6
3rd gen. Cephalosporins R . . <1 <1 1
E. faecalis Aminopenicillins I+R . . <1 <1 <1
Aminoglycosides (high-level resistance) . . 8 6 <1
Glycopeptides I+R . . <1 <1 <1
E. faecium Aminopenicillins I+R . . 40 29 57
Aminoglycosides (high-level resistance) . . <1 <1 <1
Glycopeptides I+R . . <1 <1 <1
University/tertiary care
General/secondary care
Other
Figure 1. Type of hospitals in 2002
Figure 2. Geographic distribution of laboratories in 2003
Iceland counts 9 hospitals that all report AST-results to EARSS. However,only 2 of these are relevant to EARSS with respect to denominator information,because these are the main hospitals to provide acute and general care.
IcelandDenominators
Antibiotic resistance in 1999-2003
* Based on labs/hospitals providing denominator data
*
*
*
*
*
*
APPENDIX A 79
Table 4.Details on the origin of invasive isolates in the reporting period
Characteristic S. pneumoniae
n=210
S. aureus
n=259
E. coli
n=245
E. faecalis
n=46
E. faecium
n=19
%total %PNSP %total %MRSA %total %FREC %total %VRE %total %VRE
Isolate source
Blood 95 6 100 0 100 4 100 0 100 0
CSF 5 9 0 . 0 . 0 . 0 .
Sex
Male 50 5 60 1 42 6 63 0 47 0
Female 50 7 40 0 58 3 37 0 53 0
Unknown 0 . 0 . 0 . 0 . 0 .
Age (years)
0-4 22 6 9 0 2 0 4 0 5 0
5-19 3 0 12 0 2 0 2 0 0 .
20-64 38 5 38 0 31 5 15 0 11 0
65 and over 37 6 41 1 66 4 78 0 84 0
Unknown 0 . 0 . 0 . 0 . 0 .
Hospital department
ICU 4 11 2 0 0 . 0 . 0 .
Internal Medicine 7 0 9 0 6 7 4 0 5 0
Surgery 0 . 3 0 3 14 7 0 0 .
Other 22 7 15 3 3 0 4 0 5 0
Unknown 67 6 71 0 88 4 85 0 89 0
PNSP at laboratory level MRSA at hospital level
no of hospitals : 2Minimum : 0.01st quartile : 0.0Median : 0.23rd quartile : 0.4Maximum : 0.4
no of labs : 2Minimum : 0.01st quartile : 0.0Median : 3.13rd quartile : 6.2Maximum : 6.2
Figure 4.Proportion (%) MRSA by hospital (1999-2003)
0 25 50 75 100
0/16IS003A
1/243IS001A
Figure 3.Proportion (%) PNSP by laboratory (1999-2003)
0 25 50 75 100
0/15IS003
12/195IS001
80 APPENDIX A
Table 1. Reference data of 2002
Total
Labs/Hosps reporting to EARSS 22/22
Labs/Hosps providing denom.data 21/43
Number of blood culture sets na
Number of hospital beds 9643
Average annual occupancy rate 85%Average annual occupancy rate
Estimated catchment population 3500000
% total population covered 90%
Table 2. Number of laboratories and number of isolates reported for the period 1999-2003
Year S. pneumoniae
Labs Isolates
S. aureus
Labs Isolates
E. coli
Labs Isolates
Enterococci
Labs Isolates
1999 10 154 11 511 0 0 0 0
2000 18 202 18 632 0 0 0 0
2001 21 246 19 798 0 0 0 0
2002 20 277 22 998 20 736 15 250
2003 23 362 25 1109 25 976 21 348
Table 3. Proportion of antibiotic non-susceptible isolates in percent
Pathogen Antimicrobial classes 1999 2000 2001 2002 2003
S. pneumoniae Penicillin R 3 5 2 2 3
Penicillin I+R 19 13 12 12 12
Macrolides I+R 14 12 12 13 12
S. aureus Oxacillin/Methicillin R 39 39 42 42 42
E. coli Aminopenicillins R . . . 62 61
Aminoglycosides R . . . 3 4
Fluoroquinolones R . . . 5 10
3rd gen. Cephalosporins R . . . 2 2
E. faecalis Aminopenicillins I+R . . . 8 6
Aminoglycosides (high-level resistance) . . . 39 35
Glycopeptides I+R . . . 2 1
E. faecium Aminopenicillins I+R . . . 89 89
Aminoglycosides (high-level resistance) . . . 17 54
Glycopeptides I+R . . . 11 19
University/tertiary care
General/secondary care
Other
Figure 1. Type of hospitals in 2002
Figure 2. Geographic distribution of laboratories in 2003
IrelandDenominators
Antibiotic resistance in 1999-2003
* Based on labs/hospitals providing denominator data
*
*
*
*
*
*
APPENDIX A 81
Table 4.Details on the origin of invasive isolates in the reporting period
Characteristic S. pneumoniae
n=1241
S. aureus
n=4048
E. coli
n=1671
E. faecalis
n=375
E. faecium
n=215
%total %PNSP %total %MRSA %total %FREC %total %VRE %total %VRE
Isolate source
Blood 98 13 100 41 100 8 100 2 100 16
CSF 2 24 0 . 0 . 0 . 0 .
Sex
Male 54 13 61 43 42 9 66 2 57 12
Female 44 13 36 40 57 7 33 2 42 20
Unknown 2 8 3 32 1 0 1 0 1 33
Age (years)
0-4 15 16 5 17 3 5 6 4 3 0
5-19 6 10 4 14 1 4 1 0 1 33
20-64 36 9 40 36 33 8 42 3 47 16
65 and over 42 15 48 52 61 8 50 1 48 16
Unknown 2 15 2 28 1 0 0 . 1 0
Hospital department
ICU 5 13 8 60 3 8 9 0 16 15
Internal Medicine 36 14 27 43 19 5 21 0 9 37
Surgery 2 14 12 54 6 8 10 3 6 8
Other 29 11 22 28 22 3 14 6 7 7
Unknown 27 13 32 40 49 11 47 2 63 15
PNSP at laboratory level MRSA at hospital level
no of hospitals : 23Minimum : 0.01st quartile : 31.7Median : 38.93rd quartile : 46.5Maximum : 49.7
no of labs : 21Minimum : 4.81st quartile : 9.5Median : 12.93rd quartile : 17.0Maximum : 21.4
Figure 4.Proportion (%) MRSA by hospital (1999-2003)
0 25 50 75 100
0/13IE-CX
2/30IE-VX
7/49IE-PX
7/47IE-AX
1/5IE-UX
20/63IE-ZX
22/66IE-HY
10/29IE-QZ
18/51IE-TY
138/374IE-RX
13/35IE-BX
115/296IE-XX
114/285IE-#X
283/696IE-EX
39/95IE-<X
54/125IE-FX
140/322IE-WX
119/256IE-IX
274/587IE-YX
32/68IE-OX
16/33IE-GX
156/321IE-LY
83/167IE-NX
Figure 3.Proportion (%) PNSP by laboratory (1999-2003)
0 25 50 75 100
1/21IE-V
1/19IE-B
2/31IE-<
10/126IE-L
1/11IE-A
2/21IE-Q
10/102IE-W
11/98IE-R
10/89IE-X
10/84IE-E
12/93IE-#
8/61IE-I
3/21IE-H
9/62IE-F
6/41IE-T
27/159IE-Y
7/40IE-P
5/28IE-G
2/11IE-Z
15/70IE-N
3/14IE-O
82 APPENDIX A
Table 1. Reference data of 2002
Total
Labs/Hosps reporting to EARSS 5/5
Labs/Hosps providing denom.data 5/5
Number of blood culture sets 118289
Number of hospital beds 4409
Average annual occupancy rate 97%Average annual occupancy rate
Estimated catchment population 2430000
% total population covered 40%
Table 2. Number of laboratories and number of isolates reported for the period 1999-2003
Year S. pneumoniae
Labs Isolates
S. aureus
Labs Isolates
E. coli
Labs Isolates
Enterococci
Labs Isolates
1999 0 0 0 0 0 0 0 0
2000 0 0 0 0 0 0 0 0
2001 5 170 5 381 5 741 5 184
2002 5 177 5 468 5 865 5 254
2003 5 180 5 368 5 774 5 244
Table 3. Proportion of antibiotic non-susceptible isolates in percent
Pathogen Antimicrobial classes 1999 2000 2001 2002 2003
S. pneumoniae Penicillin R . . 5 7 11
Penicillin I+R . . 40 38 38
Macrolides I+R . . 11 12 14
S. aureus Oxacillin/Methicillin R . . 39 38 43
E. coli Aminopenicillins R . . 66 62 62
Aminoglycosides R . . 17 16 14
Fluoroquinolones R . . 21 19 20
3rd gen. Cephalosporins R . . 9 8 9
E. faecalis Aminopenicillins I+R . . <1 4 2
Aminoglycosides (high-level resistance) . . 24 44 43
Glycopeptides I+R . . 1 2 <1
E. faecium Aminopenicillins I+R . . 46 50 48
Aminoglycosides (high-level resistance) . . 33 42 38
Glycopeptides I+R . . 12 10 8
University/tertiary care
General/secondary care
Other
Figure 1. Type of hospitals in 2002
Figure 2. Geographic distribution of laboratories in 2003
IsraelDenominators
Antibiotic resistance in 1999-2003
* Based on labs/hospitals providing denominator data
*
*
*
*
*
*
APPENDIX A 83
Table 4.Details on the origin of invasive isolates in the reporting period
Characteristic S. pneumoniae
n=527
S. aureus
n=1217
E. coli
n=2373
E. faecalis
n=567
E. faecium
n=99
%total %PNSP %total %MRSA %total %FREC %total %VRE %total %VRE
Isolate source
Blood 100 39 100 40 100 20 100 1 100 10
CSF 0 . 0 . 0 . 0 . 0 .
Sex
Male 57 36 60 41 41 24 57 1 55 7
Female 43 42 40 38 59 17 43 2 45 13
Unknown 0 . 0 . 0 . 0 . 0 .
Age (years)
0-4 40 54 10 27 5 4 13 0 12 8
5-19 11 22 6 16 2 23 2 0 9 22
20-64 24 20 33 37 26 18 27 3 21 5
65 and over 25 41 51 46 66 22 58 1 58 11
Unknown 1 50 0 . 0 . 0 . 0 .
Hospital department
ICU 5 32 10 45 6 26 16 1 21 10
Internal Medicine 38 31 44 40 58 19 42 1 19 11
Surgery 2 10 14 45 10 28 10 0 14 0
Other 55 46 32 35 26 19 33 2 45 13
Unknown 0 . 0 . 0 . 0 . 0 .
PNSP at laboratory level MRSA at hospital level
no of hospitals : 5Minimum : 21.21st quartile : 24.3Median : 29.43rd quartile : 39.5Maximum : 46.2
no of labs : 5Minimum : 32.41st quartile : 35.1Median : 40.23rd quartile : 41.5Maximum : 53.1
Figure 4.Proportion (%) MRSA by hospital (1999-2003)
0 25 50 75 100
25/118IL001A
28/115IL004A
20/68IL005A
79/200IL003A
331/716IL002A
Figure 3.Proportion (%) PNSP by laboratory (1999-2003)
0 25 50 75 100
12/37IL005
74/211IL003
76/189IL002
17/41IL004
26/49IL001
84 APPENDIX A
Table 1. Reference data of 2002
Total
Labs/Hosps reporting to EARSS 56/56
Labs/Hosps providing denom.data 0/0
Number of blood culture sets na
Number of hospital beds na
Average annual occupancy rate naAverage annual occupancy rate
Estimated catchment population na
% total population covered na
Table 2. Number of laboratories and number of isolates reported for the period 1999-2003
Year S. pneumoniae
Labs Isolates
S. aureus
Labs Isolates
E. coli
Labs Isolates
Enterococci
Labs Isolates
1999 41 177 56 1158 0 0 0 0
2000 36 116 48 456 0 0 0 0
2001 39 121 53 839 0 0 42 297
2002 50 296 53 1343 17 618 49 602
2003 38 201 19 394 16 669 38 425
Table 3. Proportion of antibiotic non-susceptible isolates in percent
Pathogen Antimicrobial classes 1999 2000 2001 2002 2003
S. pneumoniae Penicillin R 2 <1 4 2 5
Penicillin I+R 13 11 9 11 12
Macrolides I+R 29 28 39 32 38
S. aureus Oxacillin/Methicillin R 41 44 41 38 38
E. coli Aminopenicillins R . . . 48 51
Aminoglycosides R . . . 6 7
Fluoroquinolones R . . . 21 25
3rd gen. Cephalosporins R . . . 3 6
E. faecalis Aminopenicillins I+R . . 3 6 3
Aminoglycosides (high-level resistance) . . 31 38 36
Glycopeptides I+R . . 2 <1 2
E. faecium Aminopenicillins I+R . . 69 79 75
Aminoglycosides (high-level resistance) . . 18 37 38
Glycopeptides I+R . . 19 21 25
University/tertiary care
General/secondary care
Other
Figure 1. Type of hospitals in 2002
Figure 2. Geographic distribution of laboratories in 2003
ItalyDenominators
Antibiotic resistance in 1999-2003
* Based on labs/hospitals providing denominator data
*
*
*
*
*
*
APPENDIX A 85
Table 4.Details on the origin of invasive isolates in the reporting period
Characteristic S. pneumoniae
n=911
S. aureus
n=4190
E. coli
n=1286
E. faecalis
n=944
E. faecium
n=370
%total %PNSP %total %MRSA %total %FREC %total %VRE %total %VRE
Isolate source
Blood 81 11 100 40 100 23 100 1 100 22
CSF 19 15 0 . 0 . 0 . 0 .
Sex
Male 53 13 55 41 24 22 49 1 51 19
Female 39 8 35 37 29 22 29 1 34 22
Unknown 9 16 11 44 47 24 22 1 15 30
Age (years)
0-4 12 6 2 16 1 0 4 0 4 6
5-19 3 14 2 14 0 . 1 0 1 0
20-64 35 15 31 33 14 22 23 0 27 22
65 and over 34 9 44 43 35 22 41 2 42 17
Unknown 16 12 21 49 49 25 32 1 25 32
Hospital department
ICU 8 17 13 59 3 19 19 2 16 22
Internal Medicine 33 8 34 35 42 20 33 1 35 17
Surgery 2 16 11 50 6 26 11 3 16 17
Other 42 13 31 33 14 23 16 1 16 22
Unknown 14 13 11 40 36 27 21 0 18 33
PNSP at laboratory level MRSA at hospital level
no of hospitals : 71Minimum : 0.01st quartile : 25.0Median : 36.83rd quartile : 51.3Maximum : 73.0
no of labs : 50Minimum : 0.01st quartile : 0.0Median : 9.93rd quartile : 15.6Maximum : 50.0
Figure 4.Proportion (%) MRSA by hospital (1999-2003)
0 25 50 75 100
0/11IT006X0/7IT013X0/7IT028X
1/14IT026X6/56IT007X
6/41IT077X4/26IT023X
23/128IT019X11/55IT015X6/30IT024X
4/19IT044X2/9IT002X8/35IT029X12/51IT022X23/95IT047X31/127IT061X4/16IT004X2/8IT080X
21/79IT010X7/26IT038X
6/21IT056X75/259IT031X
6/20IT062X8/26IT036X16/52IT074X
7/22IT064X12/37IT073X19/58IT065X5/15IT050X6/18IT075X41/121IT072X
37/106IT042X18/51IT060X18/50IT035X36/100IT041X78/212IT008X24/64IT070X23/61IT059X24/63IT079X
25/64IT045X51/129IT021X28/70IT068X11/27IT052X
17/40IT027X27/63IT034X15/35IT090X
42/94IT009X13/29IT067X
11/23IT051X24/49IT032X
30/60IT016X10/20IT069X3/6IT088X
58/113IT040X73/141IT054X
63/118IT014X52/96IT025X69/126IT037X
37/66IT030X18/32IT071X24/42IT066X8/14IT085X23/40IT049X
61/98IT005X46/73IT012X30/47IT091X
15/23IT011X23/35IT089X24/36IT017X68/101IT092X
27/37IT046X
Figure 3.Proportion (%) PNSP by laboratory (1999-2003)
0 25 50 75 100
0/9IT004
0/11IT017
0/6IT023
0/5IT027
0/9IT028
0/9IT030
0/7IT032
0/17IT047
0/6IT049
0/5IT051
0/35IT061
0/13IT062
0/6IT064
0/15IT078
0/13IT079
0/5IT080
1/18IT040
1/16IT046
1/16IT054
3/45IT037
1/14IT029
1/12IT034
3/31IT019
3/31IT059
4/41IT031
1/10IT039
2/19IT005
2/18IT042
1/9IT067
2/16IT036
1/8IT091
2/15IT014
2/15IT077
3/22IT009
2/14IT070
3/20IT025
2/13IT065
5/32IT060
3/19IT035
2/12IT007
2/12IT038
4/21IT022
2/10IT021
2/10IT024
11/54IT008
5/24IT015
3/14IT072
5/21IT003
6/15IT044
3/6IT012
86 APPENDIX A
Table 1. Reference data of 2002
Total
Labs/Hosps reporting to EARSS 9/14
Labs/Hosps providing denom.data 7/6
Number of blood culture sets 10083
Number of hospital beds 1693
Average annual occupancy rate 76%Average annual occupancy rate
Estimated catchment population 449000
% total population covered 100%
Table 2. Number of laboratories and number of isolates reported for the period 1999-2003
Year S. pneumoniae
Labs Isolates
S. aureus
Labs Isolates
E. coli
Labs Isolates
Enterococci
Labs Isolates
1999 1 9 1 25 0 0 0 0
2000 5 22 4 67 0 0 0 0
2001 8 41 8 85 8 193 7 31
2002 7 27 9 95 9 193 8 30
2003 7 48 8 95 8 227 7 41
Table 3. Proportion of antibiotic non-susceptible isolates in percent
Pathogen Antimicrobial classes 1999 2000 2001 2002 2003
S. pneumoniae Penicillin R 11 <1 7 7 <1
Penicillin I+R 22 14 12 22 15
Macrolides I+R 33 26 23 22 30
S. aureus Oxacillin/Methicillin R 16 18 20 15 21
E. coli Aminopenicillins R . . 44 43 49
Aminoglycosides R . . 5 4 4
Fluoroquinolones R . . 5 10 12
3rd gen. Cephalosporins R . . <1 <1 <1
E. faecalis Aminopenicillins I+R . . <1 <1 5
Aminoglycosides (high-level resistance) . . 13 17 32
Glycopeptides I+R . . <1 <1 <1
E. faecium Aminopenicillins I+R . . <1 60 100
Aminoglycosides (high-level resistance) . . . 14 <1
Glycopeptides I+R . . <1 <1 <1
University/tertiary care
General/secondary care
Other
Figure 1. Type of hospitals in 2002
Figure 2. Geographic distribution of laboratories in 2003
LuxembourgDenominators
Antibiotic resistance in 1999-2003
* Based on labs/hospitals providing denominator data
*
*
*
*
*
*
APPENDIX A 87
Table 4.Details on the origin of invasive isolates in the reporting period
Characteristic S. pneumoniae
n=147
S. aureus
n=367
E. coli
n=574
E. faecalis
n=75
E. faecium
n=12
%total %PNSP %total %MRSA %total %FREC %total %VRE %total %VRE
Isolate source
Blood 88 16 100 18 100 9 100 0 100 0
CSF 12 11 0 . 0 . 0 . 0 .
Sex
Male 56 18 56 16 38 10 55 0 33 0
Female 44 12 40 22 53 7 43 0 58 0
Unknown 0 . 4 19 9 17 3 0 8 0
Age (years)
0-4 13 16 8 20 3 0 3 0 8 0
5-19 3 40 3 9 1 0 1 0 0 .
20-64 41 10 39 14 26 1 37 0 8 0
65 and over 42 19 46 22 62 12 56 0 75 0
Unknown 0 . 4 20 9 17 3 0 8 0
Hospital department
ICU 16 8 11 23 10 4 40 0 33 0
Internal Medicine 27 21 26 21 36 12 17 0 17 0
Surgery 3 0 10 29 4 8 8 0 0 .
Other 24 14 19 17 20 6 17 0 25 0
Unknown 30 18 34 13 30 10 17 0 25 0
PNSP at laboratory level MRSA at hospital level
no of hospitals : 9Minimum : 0.01st quartile : 12.5Median : 18.83rd quartile : 20.0Maximum : 27.4
no of labs : 7Minimum : 0.01st quartile : 12.2Median : 18.83rd quartile : 28.6Maximum : 30.0
Figure 4.Proportion (%) MRSA by hospital (1999-2003)
0 25 50 75 100
0/8LU002W
1/12LU006L
4/32LU004T
7/51LU007Z
3/16LU006A
29/145LU001E
1/5LU002P
3/14LU005I
17/62LU003S
Figure 3.Proportion (%) PNSP by laboratory (1999-2003)
0 25 50 75 100
0/5LU005
9/74LU001
2/16LU004
3/16LU006
4/16LU003
2/7LU002
3/10LU007
88 APPENDIX A
Table 1. Reference data of 2002
Total
Labs/Hosps reporting to EARSS 1/1
Labs/Hosps providing denom.data 1/1
Number of blood culture sets 2863
Number of hospital beds 846
Average annual occupancy rate 83%Average annual occupancy rate
Estimated catchment population 370000
% total population covered 93%
Table 2. Number of laboratories and number of isolates reported for the period 1999-2003
Year S. pneumoniae
Labs Isolates
S. aureus
Labs Isolates
E. coli
Labs Isolates
Enterococci
Labs Isolates
1999 0 0 0 0 0 0 0 0
2000 1 11 1 76 0 0 0 0
2001 1 12 1 83 1 67 1 13
2002 1 12 1 87 1 74 1 33
2003 1 9 1 122 1 91 1 26
Table 3. Proportion of antibiotic non-susceptible isolates in percent
Pathogen Antimicrobial classes 1999 2000 2001 2002 2003
S. pneumoniae Penicillin R . <1 <1 <1 <1
Penicillin I+R . 9 8 <1 <1
Macrolides I+R . 36 18 25 38
S. aureus Oxacillin/Methicillin R . 36 54 43 43
E. coli Aminopenicillins R . . 27 43 39
Aminoglycosides R . . 10 8 18
Fluoroquinolones R . . 15 12 24
3rd gen. Cephalosporins R . . <1 3 2
E. faecalis Aminopenicillins I+R . . 8 <1 5
Aminoglycosides (high-level resistance) . . 8 17 29
Glycopeptides I+R . . <1 <1 <1
E. faecium Aminopenicillins I+R . . 100 33 33
Aminoglycosides (high-level resistance) . . <1 <1 50
Glycopeptides I+R . . <1 <1 <1
University/tertiary care
General/secondary care
Other
Figure 1. Type of hospitals in 2002
Figure 2. Geographic distribution of laboratories in 2003
MaltaDenominators
Antibiotic resistance in 1999-2003
* Based on labs/hospitals providing denominator data
*
*
*
*
*
*
APPENDIX A 89
Table 4.Details on the origin of invasive isolates in the reporting period
Characteristic S. pneumoniae
n=44
S. aureus
n=368
E. coli
n=231
E. faecalis
n=62
E. faecium
n=10
%total %PNSP %total %MRSA %total %FREC %total %VRE %total %VRE
Isolate source
Blood 91 3 100 44 100 18 100 0 100 0
CSF 9 25 0 . 0 . 0 . 0 .
Sex
Male 70 3 57 45 45 26 61 0 30 0
Female 30 8 43 42 55 11 39 0 70 0
Unknown 0 . 1 0 0 . 0 . 0 .
Age (years)
0-4 34 0 8 18 6 13 8 0 10 0
5-19 5 0 7 15 2 20 0 . 10 0
20-64 30 8 42 40 24 18 42 0 40 0
65 and over 32 7 43 57 67 18 50 0 40 0
Unknown 0 . 0 . 1 0 0 . 0 .
Hospital department
ICU 23 10 17 55 10 0 63 0 70 0
Internal Medicine 30 8 43 37 49 21 16 0 20 0
Surgery 0 . 19 52 21 24 13 0 10 0
Other 39 0 13 27 6 7 3 0 0 .
Unknown 9 0 8 65 14 13 5 0 0 .
PNSP at laboratory level MRSA at hospital level
no of hospitals : 2Minimum : 43.41st quartile : 43.4Median : 51.73rd quartile : 60.0Maximum : 60.0
no of labs : 1Minimum : 4.51st quartile : 4.5Median : 4.53rd quartile : 4.5Maximum : 4.5
Figure 4.Proportion (%) MRSA by hospital (1999-2003)
0 25 50 75 100
155/357MT001A
3/5MT001E
Figure 3.Proportion (%) PNSP by laboratory (1999-2003)
0 25 50 75 100
2/44MT001
90 APPENDIX A
Table 1. Reference data of 2002
Total
Labs/Hosps reporting to EARSS 23/39
Labs/Hosps providing denom.data 16/22
Number of blood culture sets 113149
Number of hospital beds 13093
Average annual occupancy rate 65%Average annual occupancy rate
Estimated catchment population 5989000
% total population covered 37%
Table 2. Number of laboratories and number of isolates reported for the period 1999-2003
Year S. pneumoniae
Labs Isolates
S. aureus
Labs Isolates
E. coli
Labs Isolates
Enterococci
Labs Isolates
1999 21 762 20 1224 0 0 0 0
2000 23 740 24 1388 0 0 0 0
2001 20 723 21 1290 20 1864 14 275
2002 23 860 22 1502 22 2427 22 536
2003 21 791 20 1175 21 1915 21 419
Table 3. Proportion of antibiotic non-susceptible isolates in percent
Pathogen Antimicrobial classes 1999 2000 2001 2002 2003
S. pneumoniae Penicillin R < 1 <1 <1 <1 <1
Penicillin I+R 1 1 <1 1 <1
Macrolides I+R . 4 5 7 5
S. aureus Oxacillin/Methicillin R < 1 <1 <1 <1 <1
E. coli Aminopenicillins R . . 39 39 42
Aminoglycosides R . . 2 2 3
Fluoroquinolones R . . 6 5 7
3rd gen. Cephalosporins R . . <1 <1 1
E. faecalis Aminopenicillins I+R . . 2 3 5
Aminoglycosides (high-level resistance) . . 28 33 22
Glycopeptides I+R . . <1 1 2
E. faecium Aminopenicillins I+R . . 64 23 25
Aminoglycosides (high-level resistance) . . 4 11 18
Glycopeptides I+R . . 5 2 4
University/tertiary care
General/secondary care
Other
Figure 1. Type of hospitals in 2002
Figure 2. Geographic distribution of laboratories in 2003
NetherlandsDenominators
Antibiotic resistance in 1999-2003
* Based on labs/hospitals providing denominator data
*
*
*
*
*
*
APPENDIX A 91
Table 4.Details on the origin of invasive isolates in the reporting period
Characteristic S. pneumoniae
n=3876
S. aureus
n=6579
E. coli
n=5773
E. faecalis
n=764
E. faecium
n=427
%total %PNSP %total %MRSA %total %FREC %total %VRE %total %VRE
Isolate source
Blood 90 1 100 1 99 6 100 1 100 3
CSF 10 1 0 . 1 2 0 . 0 .
Sex
Male 54 1 57 1 46 7 61 1 62 2
Female 45 1 42 1 54 5 38 2 37 5
Unknown 1 3 1 0 0 . 1 0 1 0
Age (years)
0-4 8 2 9 1 4 1 10 0 7 0
5-19 3 2 4 0 1 5 2 0 2 0
20-64 35 1 35 1 29 8 41 2 36 3
65 and over 51 1 50 1 62 5 46 1 49 4
Unknown 2 0 2 1 4 9 1 0 5 0
Hospital department
ICU 5 2 6 1 4 10 18 1 10 0
Internal Medicine 11 1 12 0 13 6 13 1 6 8
Surgery 2 0 7 1 6 6 10 1 2 10
Other 19 2 20 0 12 6 16 1 11 0
Unknown 63 1 55 1 65 6 43 2 71 3
PNSP at laboratory level MRSA at hospital level
no of hospitals : 48Minimum : 0.01st quartile : 0.0Median : 0.03rd quartile : 0.8Maximum : 3.6
no of labs : 24Minimum : 0.01st quartile : 0.0Median : 0.63rd quartile : 2.2Maximum : 5.0
Figure 4.Proportion (%) MRSA by hospital (1999-2003)
0 25 50 75 100
0/119NL003A
0/43NL005A
0/32NL005X
0/42NL006A
0/81NL006B
0/161NL009F
0/77NL009I
0/42NL009K
0/447NL010X
0/57NL011A
0/63NL011B
0/61NL011C
0/65NL011D
0/29NL011E
0/43NL011F
0/47NL012A
0/17NL012B
0/57NL012C
0/54NL013A
0/16NL013B
0/65NL015A
0/79NL016A
0/24NL017A
0/21NL017X
0/42NL018X
0/69NL021B
0/62NL021C
1/377NL026A
1/232NL006D
1/217NL029A
1/181NL025A
1/166NL022A
2/311NL020X
1/148NL006C
1/139NL008A
2/249NL002A
1/113NL023A
3/330NL007A
2/178NL002X
4/343NL019X
1/84NL009A
3/224NL014X
5/328NL022X
1/59NL018A
2/99NL011X
2/90NL021A
1/43NL009Z
2/56NL016X
Figure 3.Proportion (%) PNSP by laboratory (1999-2003)
0 25 50 75 100
0/38NL003
0/389NL006
0/153NL007
0/33NL013
0/134NL014
0/57NL018
0/197NL021
0/36NL023
0/138NL029
1/244NL002
1/189NL008
2/364NL011
2/297NL020
3/269NL010
5/394NL009
1/75NL012
1/60NL005
4/214NL019
1/39NL017
2/57NL015
9/228NL022
2/45NL026
4/86NL025
4/80NL016
92 APPENDIX A
Table 1. Reference data of 2002
Total
Labs/Hosps reporting to EARSS 24/24
Labs/Hosps providing denom.data 0/0
Number of blood culture sets na
Number of hospital beds na
Average annual occupancy rate naAverage annual occupancy rate
Estimated catchment population 4552000
% total population covered 100%
Table 2. Number of laboratories and number of isolates reported for the period 1999-2003
Year S. pneumoniae
Labs Isolates
S. aureus
Labs Isolates
E. coli
Labs Isolates
Enterococci
Labs Isolates
1999 1 28 0 0 0 0 0 0
2000 1 388 0 0 0 0 0 0
2001 0 0 0 0 0 0 0 0
2002 25 538 25 726 25 973 25 235
2003 24 514 24 637 24 966 24 252
Table 3. Proportion of antibiotic non-susceptible isolates in percent
Pathogen Antimicrobial classes 1999 2000 2001 2002 2003
S. pneumoniae Penicillin R < 1 <1 . <1 <1
Penicillin I+R <1 2 . <1 <1
Macrolides I+R . . . 5 6
S. aureus Oxacillin/Methicillin R . . . <1 <1
E. coli Aminopenicillins R . . . 27 30
Aminoglycosides R . . . 1 <1
Fluoroquinolones R . . . 2 2
3rd gen. Cephalosporins R . . . <1 <1
E. faecalis Aminopenicillins I+R . . . 1 <1
Aminoglycosides (high-level resistance) . . . 10 14
Glycopeptides I+R . . . <1 <1
E. faecium Aminopenicillins I+R . . . 62 63
Aminoglycosides (high-level resistance) . . . 4 3
Glycopeptides I+R . . . <1 3
University/tertiary care
General/secondary care
Other
Figure 1. Type of hospitals in 2002
Figure 2. Geographic distribution of laboratories in 2003
NorwayDenominators
Antibiotic resistance in 1999-2003
* Based on labs/hospitals providing denominator data
*
*
*
*
*
*
APPENDIX A 93
Table 4.Details on the origin of invasive isolates in the reporting period
Characteristic S. pneumoniae
n=954
S. aureus
n=726
E. coli
n=973
E. faecalis
n=188
E. faecium
n=47
%total %PNSP %total %MRSA %total %FREC %total %VRE %total %VRE
Isolate source
Blood 98 2 100 0 100 2 100 1 100 0
CSF 2 0 0 . 0 . 0 . 0 .
Sex
Male 47 3 . . . . . . . .
Female 52 1 . . . . . . . .
Unknown 1 20 . . . . . . . .
Age (years)
0-4 5 5 . . . . . . . .
5-19 2 0 . . . . . . . .
20-64 44 3 . . . . . . . .
65 and over 48 2 . . . . . . . .
Unknown 0 . . . . . . . . .
Hospital department
ICU 0 . . . . . . . . .
Internal Medicine 0 . . . . . . . . .
Surgery 0 . . . . . . . . .
Other 0 . . . . . . . . .
Unknown 100 2 . . . . . . . .
PNSP at laboratory level MRSA at hospital levelFigure 4.Proportion (%) MRSA by hospital (1999-2003)
0 25 50 75 100
MRSA < 1% for all hospitals
Figure 3.Proportion (%) PNSP by laboratory (1999-2003)
0 25 50 75 100
PNSP < 1% for all laboratories
94 APPENDIX A
Table 1. Reference data of 2002
Total
Labs/Hosps reporting to EARSS 24/24
Labs/Hosps providing denom.data 24/24
Number of blood culture sets 33634
Number of hospital beds 14706
Average annual occupancy rate 77%Average annual occupancy rate
Estimated catchment population 8508000
% total population covered 22%
Table 2. Number of laboratories and number of isolates reported for the period 1999-2003
Year S. pneumoniae
Labs Isolates
S. aureus
Labs Isolates
E. coli
Labs Isolates
Enterococci
Labs Isolates
1999 0 0 0 0 0 0 0 0
2000 0 0 0 0 0 0 0 0
2001 4 6 19 151 20 103 16 57
2002 7 10 21 186 22 135 19 56
2003 11 16 24 166 25 123 16 64
Table 3. Proportion of antibiotic non-susceptible isolates in percent
Pathogen Antimicrobial classes 1999 2000 2001 2002 2003
S. pneumoniae Penicillin R . . <1 30 19
Penicillin I+R . . <1 30 19
Macrolides I+R . . <1 67 14
S. aureus Oxacillin/Methicillin R . . 15 23 19
E. coli Aminopenicillins R . . 58 52 49
Aminoglycosides R . . 5 11 10
Fluoroquinolones R . . 9 11 7
3rd gen. Cephalosporins R . . 7 6 4
E. faecalis Aminopenicillins I+R . . 5 12 <1
Aminoglycosides (high-level resistance) . . 43 41 48
Glycopeptides I+R . . <1 <1 2
E. faecium Aminopenicillins I+R . . 77 80 91
Aminoglycosides (high-level resistance) . . 73 73 55
Glycopeptides I+R . . 7 <1 <1
University/tertiary care
General/secondary care
Other
Figure 1. Type of hospitals in 2002
Figure 2. Geographic distribution of laboratories in 2003
PolandDenominators
Antibiotic resistance in 1999-2003
* Based on labs/hospitals providing denominator data
*
*
*
*
*
*
APPENDIX A 95
Table 4.Details on the origin of invasive isolates in the reporting period
Characteristic S. pneumoniae
n=32
S. aureus
n=503
E. coli
n=346
E. faecalis
n=125
E. faecium
n=52
%total %PNSP %total %MRSA %total %FREC %total %VRE %total %VRE
Isolate source
Blood 84 19 100 19 99 9 100 1 100 2
CSF 16 20 0 . 1 0 0 . 0 .
Sex
Male 53 6 61 23 42 10 62 0 46 0
Female 47 33 39 14 57 8 38 2 54 4
Unknown 0 . 0 . 0 . 0 . 0 .
Age (years)
0-4 16 20 14 17 11 0 9 0 19 0
5-19 9 67 3 36 2 14 3 0 2 0
20-64 56 11 53 22 43 13 38 0 58 3
65 and over 19 17 30 15 44 7 50 2 21 0
Unknown 0 . 0 . 0 . 0 . 0 .
Hospital department
ICU 13 0 14 37 10 12 15 0 29 0
Internal Medicine 47 20 50 16 51 9 42 0 23 8
Surgery 3 100 16 23 17 12 26 3 25 0
Other 38 17 20 14 22 4 17 0 23 0
Unknown 0 . 0 . 0 . 0 . 0 .
PNSP at laboratory level MRSA at hospital level
no of hospitals : 21Minimum : 0.01st quartile : 10.0Median : 16.13rd quartile : 23.5Maximum : 86.7
no of labs : 2Minimum : 0.01st quartile : 0.0Median : 20.03rd quartile : 40.0Maximum : 40.0
Figure 4.Proportion (%) MRSA by hospital (1999-2003)
0 25 50 75 100
0/7PL007A
0/7PL009A
0/22PL019A
0/5PL024A
1/14PL008A
1/10PL020A
2/17PL016A
7/52PL005A
4/29PL017A
6/42PL014A
5/31PL006A
1/6PL015A
8/46PL011A
7/38PL002A
2/9PL021A
4/17PL001A
14/59PL003A
10/37PL022A
3/10PL012A
4/8PL013A
13/15PL023A
Figure 3.Proportion (%) PNSP by laboratory (1999-2003)
0 25 50 75 100
0/8PL022
2/5PL005
96 APPENDIX A
Table 1. Reference data of 2002
Total
Labs/Hosps reporting to EARSS 18/18
Labs/Hosps providing denom.data 15/15
Number of blood culture sets 36481
Number of hospital beds 6577
Average annual occupancy rate 78%Average annual occupancy rate
Estimated catchment population 2305000
% total population covered 23%
Table 2. Number of laboratories and number of isolates reported for the period 1999-2003
Year S. pneumoniae
Labs Isolates
S. aureus
Labs Isolates
E. coli
Labs Isolates
Enterococci
Labs Isolates
1999 12 119 13 369 0 0 0 0
2000 11 97 8 150 0 0 0 0
2001 16 155 16 521 13 418 12 185
2002 14 182 16 543 17 444 13 101
2003 12 95 22 1033 21 792 18 398
Table 3. Proportion of antibiotic non-susceptible isolates in percent
Pathogen Antimicrobial classes 1999 2000 2001 2002 2003
S. pneumoniae Penicillin R < 1 <1 <1 <1 <1
Penicillin I+R 17 29 25 20 20
Macrolides I+R 9 11 . . .
S. aureus Oxacillin/Methicillin R 37 25 32 38 45
E. coli Aminopenicillins R . . 54 58 53
Aminoglycosides R . . 6 9 9
Fluoroquinolones R . . 18 23 26
3rd gen. Cephalosporins R . . 3 6 7
E. faecalis Aminopenicillins I+R . . 5 2 4
Aminoglycosides (high-level resistance) . . 30 25 34
Glycopeptides I+R . . 7 6 6
E. faecium Aminopenicillins I+R . . 76 79 88
Aminoglycosides (high-level resistance) . . 23 33 55
Glycopeptides I+R . . 24 . 50
University/tertiary care
General/secondary care
Other
Figure 1. Type of hospitals in 2002
Figure 2. Geographic distribution of laboratories in 2003
PortugalDenominators
Antibiotic resistance in 1999-2003
* Based on labs/hospitals providing denominator data
*
*
*
*
*
*
*
* Proportion not given, due to very low numbers of isolates.
APPENDIX A 97
Table 4.Details on the origin of invasive isolates in the reporting period
Characteristic S. pneumoniae
n=648
S. aureus
n=2616
E. coli
n=1430
E. faecalis
n=532
E. faecium
n=150
%total %PNSP %total %MRSA %total %FREC %total %VRE %total %VRE
Isolate source
Blood 80 22 100 39 99 23 100 6 100 39
CSF 20 22 0 . 1 25 0 . 0 .
Sex
Male 60 20 63 39 46 28 58 6 55 41
Female 38 24 37 39 54 20 41 7 45 37
Unknown 2 30 0 . 0 . 0 . 0 .
Age (years)
0-4 14 47 3 10 1 10 2 0 3 40
5-19 5 11 3 29 2 13 1 14 1 50
20-64 42 16 43 34 38 23 35 5 47 45
65 and over 27 16 42 49 51 27 52 8 37 38
Unknown 12 33 9 28 8 11 10 2 11 18
Hospital department
ICU 7 20 12 57 6 34 16 4 19 36
Internal Medicine 20 17 27 43 30 25 24 9 15 48
Surgery 0 . 8 55 7 20 11 2 13 30
Other 68 24 53 31 56 22 49 7 52 41
Unknown 5 21 1 26 1 21 0 . 1 0
PNSP at laboratory level MRSA at hospital level
no of hospitals : 19Minimum : 11.11st quartile : 20.8Median : 36.33rd quartile : 47.4Maximum : 63.9
no of labs : 16Minimum : 0.01st quartile : 14.0Median : 19.53rd quartile : 26.1Maximum : 50.0
Figure 4.Proportion (%) MRSA by hospital (1999-2003)
0 25 50 75 100
3/27PT004A
4/30PT021A
13/67PT016A
76/372PT011A
5/24PT022A
32/101PT018A
52/164PT019A
123/379PT003A
38/109PT015A
49/135PT005A
42/106PT008A
6/15PT027A
42/97PT007A
56/124PT012A
64/135PT001A
6/12PT024A
72/136PT002A
7/13PT006A
156/244PT017A
Figure 3.Proportion (%) PNSP by laboratory (1999-2003)
0 25 50 75 100
0/6PT012
0/22PT024
1/11PT016
3/23PT017
3/20PT015
17/102PT003
7/39PT002
7/37PT005
1/5PT013
11/53PT001
5/24PT007
30/127PT011
16/56PT019
13/40PT018
15/42PT008
4/8PT009
98 APPENDIX A
Table 1. Reference data of 2002
Total
Labs/Hosps reporting to EARSS 12/11
Labs/Hosps providing denom.data 8/8
Number of blood culture sets 10515
Number of hospital beds 6201
Average annual occupancy rate 87%Average annual occupancy rate
Estimated catchment population 10243000
% total population covered 46%
Table 2. Number of laboratories and number of isolates reported for the period 1999-2003
Year S. pneumoniae
Labs Isolates
S. aureus
Labs Isolates
E. coli
Labs Isolates
Enterococci
Labs Isolates
1999 0 0 0 0 0 0 0 0
2000 0 0 0 0 0 0 0 0
2001 0 0 0 0 0 0 0 0
2002 6 10 11 81 8 28 4 11
2003 4 22 9 85 9 50 5 12
Table 3. Proportion of antibiotic non-susceptible isolates in percent
Pathogen Antimicrobial classes 1999 2000 2001 2002 2003
S. pneumoniae Penicillin R . . . 10 23
Penicillin I+R . . . 50 36
Macrolides I+R . . . 10 27
S. aureus Oxacillin/Methicillin R . . . 36 46
E. coli Aminopenicillins R . . . 64 66
Aminoglycosides R . . . 19 21
Fluoroquinolones R . . . 21 14
3rd gen. Cephalosporins R . . . 18 19
E. faecalis Aminopenicillins I+R . . . <1 <1
Aminoglycosides (high-level resistance) . . . 40 25
Glycopeptides I+R . . . <1 <1
E. faecium Aminopenicillins I+R . . . 100 86
Aminoglycosides (high-level resistance) . . . 80 63
Glycopeptides I+R . . . 17 <1
University/tertiary care
General/secondary care
Other
Figure 1. Type of hospitals in 2002
Figure 2. Geographic distribution of laboratories in 2003
RomaniaDenominators
Antibiotic resistance in 1999-2003
* Based on labs/hospitals providing denominator data
*
*
*
*
*
*
APPENDIX A 99
Table 4.Details on the origin of invasive isolates in the reporting period
Characteristic S. pneumoniae
n=32
S. aureus
n=166
E. coli
n=78
E. faecalis
n=9
E. faecium
n=14
%total %PNSP %total %MRSA %total %FREC %total %VRE %total %VRE
Isolate source
Blood 78 28 100 41 99 17 100 0 100 7
CSF 22 86 0 . 1 0 0 . 0 .
Sex
Male 63 30 65 40 58 24 33 0 21 33
Female 38 58 35 43 41 6 67 0 79 0
Unknown 0 . 0 . 1 0 0 . 0 .
Age (years)
0-4 28 67 26 49 15 17 22 0 50 0
5-19 16 0 17 17 14 55 11 0 21 0
20-64 41 46 39 45 37 7 22 0 7 100
65 and over 16 20 9 33 29 13 44 0 7 0
Unknown 0 . 8 57 4 0 0 . 14 0
Hospital department
ICU 0 . 4 100 1 0 0 . 0 .
Internal Medicine 0 . 6 20 5 0 0 . 0 .
Surgery 0 . 2 100 1 0 0 . 0 .
Other 69 36 39 36 81 17 56 0 36 0
Unknown 31 50 49 40 12 22 44 0 64 11
PNSP at laboratory level MRSA at hospital level
no of hospitals : 6Minimum : 25.01st quartile : 37.5Median : 41.43rd quartile : 42.4Maximum : 50.0
no of labs : 2Minimum : 38.91st quartile : 38.9Median : 49.43rd quartile : 60.0Maximum : 60.0
Figure 4.Proportion (%) MRSA by hospital (1999-2003)
0 25 50 75 100
4/16RO01EX
6/16RO01CX
11/27RO01BX
8/19RO01FX
14/33RO01AX
4/8RO08AX
Figure 3.Proportion (%) PNSP by laboratory (1999-2003)
0 25 50 75 100
7/18RO01A
3/5RO01B
100 APPENDIX A
Table 1. Reference data of 2002
Total
Labs/Hosps reporting to EARSS 14/14
Labs/Hosps providing denom.data 14/14
Number of blood culture sets 15207
Number of hospital beds 11502
Average annual occupancy rate 67%Average annual occupancy rate
Estimated catchment population 5117000
% total population covered 94%
Table 2. Number of laboratories and number of isolates reported for the period 1999-2003
Year S. pneumoniae
Labs Isolates
S. aureus
Labs Isolates
E. coli
Labs Isolates
Enterococci
Labs Isolates
1999 0 0 0 0 0 0 0 0
2000 0 0 0 0 0 0 0 0
2001 4 6 7 37 8 45 6 17
2002 9 16 14 259 14 215 12 79
2003 14 27 16 267 16 239 10 75
Table 3. Proportion of antibiotic non-susceptible isolates in percent
Pathogen Antimicrobial classes 1999 2000 2001 2002 2003
S. pneumoniae Penicillin R . . <1 19 4
Penicillin I+R . . <1 19 11
Macrolides I+R . . 20 29 <1
S. aureus Oxacillin/Methicillin R . . 5 8 12
E. coli Aminopenicillins R . . 36 51 54
Aminoglycosides R . . 2 4 6
Fluoroquinolones R . . 16 14 20
3rd gen. Cephalosporins R . . 7 2 <1
E. faecalis Aminopenicillins I+R . . <1 4 <1
Aminoglycosides (high-level resistance) . . 58 34 35
Glycopeptides I+R . . <1 3 <1
E. faecium Aminopenicillins I+R . . 67 75 92
Aminoglycosides (high-level resistance) . . 50 75 60
Glycopeptides I+R . . <1 <1 <1
University/tertiary care
General/secondary care
Other
Figure 1. Type of hospitals in 2002
Figure 2.Geographic distribution of laboratories in 2003
SlovakiaDenominators
Antibiotic resistance in 1999-2003
* Based on labs/hospitals providing denominator data
*
*
*
*
*
*
APPENDIX A 101
Table 4.Details on the origin of invasive isolates in the reporting period
Characteristic S. pneumoniae
n=49
S. aureus
n=563
E. coli
n=497
E. faecalis
n=151
E. faecium
n=19
%total %PNSP %total %MRSA %total %FREC %total %VRE %total %VRE
Isolate source
Blood 69 15 100 10 100 17 100 1 100 0
CSF 31 7 0 . 0 . 0 . 0 .
Sex
Male 55 11 60 11 43 17 55 1 53 0
Female 45 14 40 8 57 17 45 1 47 0
Unknown 0 . 0 . 0 . 0 . 0 .
Age (years)
0-4 22 27 5 19 4 5 5 0 11 0
5-19 10 0 3 12 1 0 6 0 5 0
20-64 47 4 49 8 38 19 48 3 53 0
65 and over 20 20 43 11 57 17 40 0 32 0
Unknown 0 . 0 . 0 . 0 . 0 .
Hospital department
ICU 10 0 11 13 8 18 18 4 16 0
Internal Medicine 24 17 48 9 45 18 32 0 21 0
Surgery 2 0 11 10 13 15 13 0 16 0
Other 63 13 29 11 34 17 36 2 47 0
Unknown 0 . 0 . 0 . 0 . 0 .
PNSP at laboratory level MRSA at hospital level
no of hospitals : 7Minimum : 0.01st quartile : 0.0Median : 3.83rd quartile : 9.5Maximum : 23.1
no of labs : 5Minimum : 0.01st quartile : 0.0Median : 0.03rd quartile : 11.1Maximum : 40.0
Figure 4.Proportion (%) MRSA by hospital (1999-2003)
0 25 50 75 100
0/7SK001A
0/30SK006A
0/15SK011A
1/26SK005A
3/32SK004A
4/42SK002A
6/26SK003A
Figure 3.Proportion (%) PNSP by laboratory (1999-2003)
0 25 50 75 100
0/8SK005
0/5SK010
0/6SK011
1/9SK002
2/5SK004
102 APPENDIX A
Table 1. Reference data of 2002
Total
Labs/Hosps reporting to EARSS 11/15
Labs/Hosps providing denom.data 11/15
Number of blood culture sets 28092
Number of hospital beds 7960
Average annual occupancy rate 73%Average annual occupancy rate
Estimated catchment population 1933000
% total population covered 100%
Table 2. Number of laboratories and number of isolates reported for the period 1999-2003
Year S. pneumoniae
Labs Isolates
S. aureus
Labs Isolates
E. coli
Labs Isolates
Enterococci
Labs Isolates
1999 0 0 0 0 0 0 0 0
2000 7 40 10 154 0 0 0 0
2001 10 156 10 270 10 398 10 54
2002 11 101 11 276 11 409 9 45
2003 11 172 11 299 11 401 10 76
Table 3. Proportion of antibiotic non-susceptible isolates in percent
Pathogen Antimicrobial classes 1999 2000 2001 2002 2003
S. pneumoniae Penicillin R . <1 <1 <1 2
Penicillin I+R . 23 20 19 15
Macrolides I+R . 12 18 10 9
S. aureus Oxacillin/Methicillin R . 21 20 14 13
E. coli Aminopenicillins R . . 44 43 41
Aminoglycosides R . . 2 3 2
Fluoroquinolones R . . 8 12 11
3rd gen. Cephalosporins R . . <1 1 <1
E. faecalis Aminopenicillins I+R . . <1 <1 <1
Aminoglycosides (high-level resistance) . . 35 50 49
Glycopeptides I+R . . <1 <1 <1
E. faecium Aminopenicillins I+R . . 64 69 83
Aminoglycosides (high-level resistance) . . 50 62 82
Glycopeptides I+R . . <1 <1 4
University/tertiary care
General/secondary care
Other
Figure 1. Type of hospitals in 2002
Figure 2. Geographic distribution of laboratories in 2003
SloveniaDenominators
Antibiotic resistance in 1999-2003
* Based on labs/hospitals providing denominator data
*
*
*
*
*
*
APPENDIX A 103
Table 4.Details on the origin of invasive isolates in the reporting period
Characteristic S. pneumoniae
n=469
S. aureus
n=999
E. coli
n=1208
E. faecalis
n=125
E. faecium
n=50
%total %PNSP %total %MRSA %total %FREC %total %VRE %total %VRE
Isolate source
Blood 92 18 100 16 100 10 100 0 100 2
CSF 8 16 0 . 0 . 0 . 0 .
Sex
Male 65 17 58 18 39 12 58 0 58 0
Female 35 19 42 13 61 9 42 0 42 5
Unknown 0 . 0 . 0 . 0 . 0 .
Age (years)
0-4 21 26 4 0 4 2 17 0 2 0
5-19 6 20 4 5 2 13 1 0 0 .
20-64 40 15 39 14 33 11 28 0 42 0
65 and over 32 16 52 20 62 11 54 0 56 4
Unknown 0 . 0 . 0 . 0 . 0 .
Hospital department
ICU 13 13 14 33 9 17 12 0 22 0
Internal Medicine 36 19 48 12 54 10 35 0 44 5
Surgery 1 0 13 31 6 10 11 0 4 0
Other 50 19 25 6 32 9 42 0 30 0
Unknown 0 . 0 . 0 . 0 . 0 .
PNSP at laboratory level MRSA at hospital level
no of hospitals : 12Minimum : 0.01st quartile : 10.5Median : 17.53rd quartile : 21.1Maximum : 31.6
no of labs : 11Minimum : 0.01st quartile : 14.3Median : 16.73rd quartile : 20.5Maximum : 35.7
Figure 4.Proportion (%) MRSA by hospital (1999-2003)
0 25 50 75 100
0/15SI011A
1/21SI006A
10/119SI003A
3/24SI010A
56/377SI001A
12/70SI009A
7/39SI007A
9/46SI002A
23/115SI008A
2/9SI003B
27/121SI004A
12/38SI005A
Figure 3.Proportion (%) PNSP by laboratory (1999-2003)
0 25 50 75 100
0/9SI005
0/9SI011
1/7SI006
5/32SI009
29/183SI001
4/24SI008
9/47SI010
11/56SI003
15/73SI004
5/15SI007
5/14SI002
104 APPENDIX A
Table 1. Reference data of 2002
Total
Labs/Hosps reporting to EARSS 37/37
Labs/Hosps providing denom.data 28/28
Number of blood culture sets 136260
Number of hospital beds 14043
Average annual occupancy rate 82%Average annual occupancy rate
Estimated catchment population 7714000
% total population covered 19%
Table 2.Number of laboratories and number of isolates reported for the period 1999-2003
Year S. pneumoniae
Labs Isolates
S. aureus
Labs Isolates
E. coli
Labs Isolates
Enterococci
Labs Isolates
1999 0 0 0 0 0 0 0 0
2000 33 584 30 836 0 0 0 0
2001 36 649 35 1013 27 1967 26 371
2002 35 658 36 1196 28 2483 35 566
2003 37 654 39 1391 32 2651 38 608
Table 3. Proportion of antibiotic non-susceptible isolates in percent
Pathogen Antimicrobial classes 1999 2000 2001 2002 2003
S. pneumoniae Penicillin R . 11 11 10 7
Penicillin I+R . 33 37 33 32
Macrolides I+R . 22 31 26 27
S. aureus Oxacillin/Methicillin R . 28 23 23 24
E. coli Aminopenicillins R . . 59 60 58
Aminoglycosides R . . 7 8 7
Fluoroquinolones R . . 17 19 21
3rd gen. Cephalosporins R . . <1 2 4
E. faecalis Aminopenicillins I+R . . 3 2 1
Aminoglycosides (high-level resistance) . . 32 37 36
Glycopeptides I+R . . 2 <1 <1
E. faecium Aminopenicillins I+R . . 49 59 64
Aminoglycosides (high-level resistance) . . 15 16 11
Glycopeptides I+R . . 2 4 4
University/tertiary care
General/secondary care
Other
Figure 1. Type of hospitals in 2002
Figure 2. Geographic distribution of laboratories in 2003
SpainDenominators
Antibiotic resistance in 1999-2003
* Based on labs/hospitals providing denominator data
*
*
*
*
*
*
APPENDIX A 105
Table 4.Details on the origin of invasive isolates in the reporting period
Characteristic S. pneumoniae
n=2545
S. aureus
n=4436
E. coli
n=7079
E. faecalis
n=1264
E. faecium
n=279
%total %PNSP %total %MRSA %total %FREC %total %VRE %total %VRE
Isolate source
Blood 94 34 100 24 100 19 100 1 100 4
CSF 6 37 0 . 0 . 0 . 0 .
Sex
Male 63 32 64 25 49 22 63 1 58 4
Female 37 36 35 23 50 16 37 0 41 4
Unknown 0 . 1 55 0 . 0 . 1 0
Age (years)
0-4 17 53 4 8 3 9 10 0 14 3
5-19 4 22 4 10 2 11 2 0 3 14
20-64 37 26 39 22 29 17 32 1 33 3
65 and over 41 34 52 29 65 21 55 1 50 4
Unknown 2 38 1 19 1 16 0 . 0 .
Hospital department
ICU 7 28 13 36 4 22 24 1 16 2
Internal Medicine 32 32 33 26 34 20 25 1 21 2
Surgery 1 13 11 30 8 16 8 1 14 3
Other 58 36 41 18 53 19 42 1 48 5
Unknown 2 32 2 26 1 15 1 0 2 0
PNSP at laboratory level MRSA at hospital level
no of hospitals : 36Minimum : 0.01st quartile : 12.5Median : 19.13rd quartile : 26.8Maximum : 60.5
no of labs : 37Minimum : 4.01st quartile : 27.8Median : 33.83rd quartile : 42.4Maximum : 55.6
Figure 4.Proportion (%) MRSA by hospital (1999-2003)
0 25 50 75 100
0/17ES045A
0/17ES051A
4/79ES005A
2/38ES020A
4/70ES013A
6/102ES011A
2/24ES015A
6/53ES040A
8/68ES047A
12/90ES021A
14/104ES043A
2/14ES034A
5/31ES018A
6/35ES003A
23/130ES044A
7/38ES046A
26/139ES016A
25/131ES038A
9/47ES032A
7/36ES014A
23/111ES048A
15/71ES031A
23/103ES042A
13/56ES017A
27/115ES008A
31/120ES007A
33/127ES041A
45/163ES001A
19/68ES004A
29/103ES012A
69/217ES019A
55/171ES009A
25/74ES002A
25/63ES029A
59/131ES049A
104/172ES026A
Figure 3.Proportion (%) PNSP by laboratory (1999-2003)
0 25 50 75 100
1/25ES047
9/44ES043
26/107ES011
11/45ES021
6/24ES018
22/88ES044
6/23ES015
8/30ES005
8/30ES031
5/18ES003
10/33ES046
12/39ES002
5/16ES049
50/159ES050
18/57ES009
20/63ES012
40/125ES040
4/12ES034
44/130ES001
17/50ES048
16/47ES014
24/68ES016
63/177ES042
30/81ES019
10/27ES032
38/95ES010
8/20ES045
25/59ES007
6/13ES041
11/23ES017
13/27ES008
4/8ES026
8/15ES029
7/13ES013
26/48ES038
36/65ES020
5/9ES004
106 APPENDIX A
Table 1. Reference data of 2002
Total
Labs/Hosps reporting to EARSS 21/63
Labs/Hosps providing denom.data 20/57
Number of blood culture sets 176079
Number of hospital beds 18447
Average annual occupancy rate 88%Average annual occupancy rate
Estimated catchment population 6276000
% total population covered 71%
Table 2. Number of laboratories and number of isolates reported for the period 1999-2003
Year S. pneumoniae
Labs Isolates
S. aureus
Labs Isolates
E. coli
Labs Isolates
Enterococci
Labs Isolates
1999 24 805 24 1320 0 0 0 0
2000 19 803 19 1478 0 0 0 0
2001 20 788 21 1633 20 2800 20 671
2002 21 830 21 1836 21 3066 21 696
2003 21 916 21 1854 22 3349 21 850
Table 3. Proportion of antibiotic non-susceptible isolates in percent
Pathogen Antimicrobial classes 1999 2000 2001 2002 2003
S. pneumoniae Penicillin R < 1 <1 <1 <1 <1
Penicillin I+R 1 2 3 2 5
Macrolides I+R 6 3 5 6 4
S. aureus Oxacillin/Methicillin R < 1 <1 <1 <1 <1
E. coli Aminopenicillins R . . 27 25 28
Aminoglycosides R . . <1 <1 1
Fluoroquinolones R . . 4 5 7
3rd gen. Cephalosporins R . . <1 <1 <1
E. faecalis Aminopenicillins I+R . . <1 1 <1
Aminoglycosides (high-level resistance) . . . . 17
Glycopeptides I+R . . <1 <1 <1
E. faecium Aminopenicillins I+R . . 75 75 77
Aminoglycosides (high-level resistance) . . . . 11
Glycopeptides I+R . . <1 <1 2
University/tertiary care
General/secondary care
Other
Figure 1. Type of hospitals in 2002
Figure 2. Geographic distribution of laboratories in 2003
SwedenDenominators
Antibiotic resistance in 1999-2003
* Based on labs/hospitals providing denominator data
*
*
*
*
*
*
APPENDIX A 107
Table 4.Details on the origin of invasive isolates in the reporting period
Characteristic S. pneumoniae
n=4142
S. aureus
n=8121
E. coli
n=7807
E. faecalis
n=1418
E. faecium
n=581
%total %PNSP %total %MRSA %total %FREC %total %VRE %total %VRE
Isolate source
Blood 97 3 100 1 100 5 100 0 100 1
CSF 3 4 0 . 0 . 0 . 0 .
Sex
Male 50 3 59 1 45 6 66 0 57 2
Female 48 3 38 1 52 5 30 0 40 0
Unknown 2 2 3 0 3 2 4 0 3 0
Age (years)
0-4 5 2 4 1 1 1 6 0 3 0
5-19 2 2 4 0 1 3 1 0 1 0
20-64 43 2 34 1 24 7 24 0 30 2
65 and over 50 3 58 1 73 5 69 0 65 1
Unknown 0 . 0 . 0 . 0 . 0 .
Hospital department
ICU 9 3 7 1 4 4 8 0 10 0
Internal Medicine 42 3 44 0 40 5 32 0 38 1
Surgery 4 1 15 1 20 4 26 0 28 1
Other 44 3 34 1 35 6 34 0 24 1
Unknown 1 0 1 0 0 . 0 . 0 .
PNSP at laboratory level MRSA at hospital level
no of hospitals : 63Minimum : 0.01st quartile : 0.0Median : 0.03rd quartile : 0.6Maximum : 3.3
no of labs : 21Minimum : 0.81st quartile : 1.6Median : 2.33rd quartile : 3.7Maximum : 17.5
Figure 4.Proportion (%) MRSA by hospital (1999-2003)
0 25 50 75 100
0/50SE100C0/131SE110A0/39SE110B0/82SE200C0/9SE200D0/36SE220C0/17SE220D0/33SE230B0/190SE240A0/40SE240B0/81SE240C0/102SE250B0/26SE300B0/40SE320B0/22SE320C0/51SE350B0/300SE400A0/68SE400C0/6SE400D0/18SE430B0/17SE430C0/41SE430D0/83SE440B0/72SE440C0/247SE450A0/59SE450C0/63SE450D0/30SE450E0/32SE600C0/258SE610A0/75SE610B0/126SE610C0/16SE620B0/78SE620C0/13SE620D0/24SE730A0/28SE730B0/30SE730C0/18SE730D0/37SE730E0/90SE730F1/357SE200A1/275SE430A1/253SE350A2/422SE310A2/413SE120A1/194SE200B1/167SE400B1/147SE220A1/130SE230A3/365SE440A2/225SE320A1/108SE540A3/299SE620A4/358SE600A1/72SE220B1/63SE350C1/52SE120B3/155SE250A6/230SE100B20/721SE100A1/34SE450B6/181SE300A
Figure 3.Proportion (%) PNSP by laboratory (1999-2003)
0 25 50 75 100
2/261SE400
2/194SE600
2/178SE610
3/244SE310
2/126SE300
3/184SE430
3/180SE350
2/115SE250
5/245SE450
4/190SE320
4/171SE240
8/300SE440
5/174SE620
4/139SE220
16/484SE100
13/356SE200
3/78SE730
3/76SE110
4/85SE230
15/255SE120
10/57SE540
108 APPENDIX A
Table 1. Reference data of 2002
Total
Labs/Hosps reporting to EARSS 23/26
Labs/Hosps providing denom.data 18/18
Number of blood culture sets 141543
Number of hospital beds 13664
Average annual occupancy rate 82%Average annual occupancy rate
Estimated catchment population 9685000
% total population covered 16%
Table 2. Number of laboratories and number of isolates reported for the period 1999-2003
Year S. pneumoniae
Labs Isolates
S. aureus
Labs Isolates
E. coli
Labs Isolates
Enterococci
Labs Isolates
1999 22 240 23 653 0 0 0 0
2000 28 503 27 1495 0 0 0 0
2001 26 569 25 1518 0 0 0 0
2002 23 615 21 1706 0 0 0 0
2003 50 1298 51 3493 0 0 0 0
Table 3. Proportion of antibiotic non-susceptible isolates in percent
Pathogen Antimicrobial classes 1999 2000 2001 2002 2003
S. pneumoniae Penicillin R 4 4 3 3 1
Penicillin I+R 7 6 4 5 4
Macrolides I+R 15 18 13 13 13
S. aureus Oxacillin/Methicillin R 33 40 44 44 43
E. coli Aminopenicillins R . . . . .
Aminoglycosides R . . . . .
Fluoroquinolones R . . . . .
3rd gen. Cephalosporins R . . . . .
E. faecalis Aminopenicillins I+R . . . . .
Aminoglycosides (high-level resistance) . . . . .
Glycopeptides I+R . . . . .
E. faecium Aminopenicillins I+R . . . . .
Aminoglycosides (high-level resistance) . . . . .
Glycopeptides I+R . . . . .
University/tertiary care
General/secondary care
Other
Figure 1. Type of hospitals in 2002
Figure 2. Geographic distribution of laboratories in 2003
United KingdomDenominators
Antibiotic resistance in 1999-2003
* Based on labs/hospitals providing denominator data
*
*
*
*
*
*
APPENDIX A 109
Table 4.Details on the origin of invasive isolates in the reporting period
Characteristic S. pneumoniae
n=3225
S. aureus
n=8865
E. coli
n=0
E. faecalis
n=0
E. faecium
n=0
%total %PNSP %total %MRSA %total %FREC %total %VRE %total %VRE
Isolate source
Blood 97 5 100 42 . . . . . .
CSF 3 6 0 . . . . . . .
Sex
Male 45 5 58 44 . . . . . .
Female 41 5 35 40 . . . . . .
Unknown 14 4 6 42 . . . . . .
Age (years)
0-4 11 6 4 8 . . . . . .
5-19 4 4 3 14 . . . . . .
20-64 27 5 34 36 . . . . . .
65 and over 42 5 51 51 . . . . . .
Unknown 16 4 8 39 . . . . . .
Hospital department
ICU 5 5 8 66 . . . . . .
Internal Medicine 33 5 40 41 . . . . . .
Surgery 2 5 11 56 . . . . . .
Other 38 5 33 33 . . . . . .
Unknown 22 5 8 43 . . . . . .
PNSP at laboratory level MRSA at hospital level
no of hospitals : 30Minimum : 8.41st quartile : 33.9Median : 42.03rd quartile : 50.6Maximum : 92.3
no of labs : 27Minimum : 0.01st quartile : 3.0Median : 5.13rd quartile : 8.8Maximum : 18.8
Figure 4.Proportion (%) MRSA by hospital (1999-2003)
0 25 50 75 100
13/155UK030A
26/106UK001A
56/194UK025A
58/195UK020A
57/188UK011A
5/15UK033A
5/15UK038A
230/679UK005A
180/525UK026A
140/395UK017A
28/77UK002A
22/60UK010A
66/171UK015A
30/77UK016A
79/189UK034A
192/456UK038B
84/196UK044A
148/338UK023A
433/966UK007A
14/30UK008A
200/418UK017B
178/358UK032A
243/480UK012A
72/124UK031A
65/111UK037A
6/10UK029A
79/130UK027A
287/464UK022A
21/32UK005B
36/39UK004A
Figure 3.Proportion (%) PNSP by laboratory (1999-2003)
0 25 50 75 100
0/15UK016
1/95UK015
1/66UK034
2/126UK004
3/157UK032
8/347UK007
2/66UK025
3/97UK022
5/121UK023
3/71UK001
2/43UK010
9/182UK038
7/140UK012
5/99UK030
4/79UK027
9/172UK017
3/55UK002
2/35UK026
4/64UK031
4/58UK033
6/68UK020
1/11UK009
6/63UK011
7/71UK008
24/241UK005
4/38UK044
3/16UK037
Appendix B Technical Notes
Notes to Country Summary Sheets (Appendix A)
Inclusion criteria. To be included in the analyses presented in Table 1 of the country summary sheets (Appendix A),countries, laboratories and hospitals had to provide both denominator data and AST results in 2002.Also, a laboratory had to indicate blood culture frequencies and the number of hospital beds for eachhospital served.
Presentation of variables per country.Catchment population, number of beds, and number of blood culture sets were aggregated bycountry. If ranges were given for catchment population, occupancy rate, or number of blood culturebottles per set, means were used instead (e.g. 1 to 3 = 2).
Formulas. From each hospital, either hospital occupancy rate or the number of patient-days was required.Occupancy rates could then be derived from patient-days, and vice versa.Hospital occupancy rate was calculated if not provided or if the occupancy was considered im-plausible (i.e. less than 25% or more than 125%). The following formula was used:
no. of patient-days / (no. of beds � 365). The average occupancy rate per country was calculated as follows:
[∑ (occupancy rate � no. of beds) / ∑ (no. of beds)]
For calculation of the total catchment population, hospitals providing only a specific (superregional)type of care (classified as other, e.g. oncology or psychiatric hospitals) were not included becausewe considered this population as probably overlapping with the catchment populations of thehospitals providing general care.
Population coverage per country was calculated using the following formula:∑ (hospital catchment population) / total population
The total population of mid 2002 was obtained from the CIA World Fact book.
APPENDIX B Technical notes 111
112