Download SOCIETY Assembly of Members 2008 - UEMS

2 /2008
ESCMID
NEWS
SOCIETY
Assembly of Members 2008 –
Minutes
SCIENCE AND EDUCATION
The Best of the 18th ECCMID 2008
125-Year Anniversary of
Christian Gram’s Staining Method
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Editorial
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Editorial
Assembly of Members 2008 – Minutes
ESCMID Awards, Fellowships and Grants
2009
From the Executive
18th ECCMID 2008: Results of the
Opinion Poll
First European Day of Fighting Infection
ECCMID Photo Gallery Barcelona
From the CMI Editorial Office
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European Council Meeting 2008 – Minutes
UEMS: Medical Microbiology Now an
Independent Section
Moving forward in Co-operation: Join the
Debate on Our Professional Future
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The Best of the 18th ECCMID 2008
Workshop Report: Latin American Workshop
on Mechanisms of Resistance to Antimicrobial Agents
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Course Reports:
– Postgraduate Education Course on
Infections with Multiresistant Pathogens:
Microbiological, Clinical and Therapeutic
Aspects
– Postgraduate Technical Workshop on
Gene Expression during Infection
ESCMID Young Investigator Awardees for
Research in Clinical Microbiology and
Infectious Diseases 2008:
– Profile of Sylvain Brisse
– Profile of William Hope
Reports on Training in a Foreign Institution:
– Infections Susceptibility in Senescent
Microglial Cells
– A View into Communicable Disease
Control in Malaysia
125-Year Anniversary of Christian Gram’s
Staining Method
Making Sense of Microbial Typing for
Infection Control: ESGEM and the New
Guidelines
GRACE and ECCMID
Erratum
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Forthcoming Events
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Gunnar Kahlmeter,
Chairman of EUCAST and
ESCMID Professional Affairs
Officer for Clinical Microbiology,
[email protected]
A microorganism can be categorized as susceptible to an antibiotic only after phenotypic antimicrobial susceptibility testing
(AST) based on MIC determination. Antimicrobial resistance
can be detected by phenotypic methods and /or by the detection
of a specific gene or resistance mechanism. The absence of a
specific resistance mechanism or gene can never be taken to imply that a microorganism is susceptible.
Through MIC determination or disk diffusion testing, the
drug’s ability to inhibit the growth of the microorganism is quantified. To categorize bacteria as susceptible or resistant, an AST
system requires the definition of breakpoint concentrations. In
Europe there are six national breakpoint committees (France,
Germany, Norway, Sweden, Netherlands and United Kingdom).
Together with ESCMID and the European Centre for Disease
Prevention and Control (ECDC) they organize EUCAST (read
about EUCAST on www.eucast.org). It is tasked with harmonizing European breakpoints and methods and with working closely
with the European Medicines Agency (EMEA) to determine
breakpoints for new antimicrobials. In the USA, the CLSI (Clinical Laboratory Standards Institute; formerly NCCLS) and FDA
(Food and Drug Administration) both determine breakpoints and
CLSI defines methodology and zone-diameter correlates.
EUCAST and its subcommittee on antifungal susceptibility
testing have harmonized breakpoints for existing antimicrobial
agents and, together with EMEA, have set breakpoints for several new drugs. EUCAST breakpoints are now the only breakpoints in the European Specifications of Product Characteristics
(SPCs).
European countries without national committees have often
subscribed to CLSI breakpoints and AST methodology. Only
rarely has this been a national decision; more often it has evolved
as a tradition among colleagues because there was no obvious
alternative. This resulted in the use of seven systems in Europe.
With the gradual harmonization of European breakpoints, this is
now reduced to two – European breakpoints in France, Germany,
Norway, Sweden, the Netherlands and the United Kingdom and
CLSI breakpoints in most other European countries. Manufacturers of devices for automated AST estimate that EUCAST
breakpoints will be available in the machines during 2009.
In the light of the disastrous developments in antimicrobial
resistance, the lack of truly new antimicrobial drugs in the pipeline and the failure to decisively reduce the consumption of antimicrobials, it is time for coherent European strategies and coun-
termeasures. Patient care in Europe can only benefit from
common definitions. Antimicrobial resistance surveillance programmes can only gain in stature and credibility when resistance
rates from different countries mean the same thing. The European Antimicrobial Resistance Surveillance System (EARSS) collects antimicrobial resistance data in the form of S, I or R on selected invasive pathogens from all European countries. The fact
that the categorizations are based on different breakpoints rules
out the use of some of the collected data. Analysis of the relationship between consumption and resistance is hampered by the
lack of international agreement.
It is little to ask that we all use the same yardstick when measuring antimicrobial resistance. The national breakpoint committees in Europe, ESCMID and the EU (DG Sanco and ECDC)
have invested much time and resources to achieve a common set
of European breakpoints, and now we are almost ready to provide what is needed. There is an internationally agreed International Standards Organisation (ISO) reference method for the
determination of MICs. Clinical breakpoints for existing drugs
have been harmonized and are available on the EUCAST website, together with documents describing the rationale for our
decision and links to distributions of MIC values for microorganisms without resistance mechanisms. The website also provides rules for interpretative reading of susceptibility test results;
the rules have been assembled and assessed by a EUCAST subcommittee. The manufacturers of automated devices for AST are
working hard to provide systems with European breakpoints by
2009.
But two more things are needed:
– Each country needs to adopt a national strategy for susceptibility testing. Many countries have some form of “National
Antibiotic Committee (NAC)” and those that do not are encouraged to form one during 2008 / 2009. The NAC may be
empowered to develop national strategies and recommendations for one or more fields related to antimicrobials. One of
these fields should be antimicrobial susceptibility testing. A
person from the NAC would be a natural representative on
the EUCAST General Committee. EUCAST and ESCMID
will, if requested, help form NACs.
– EUCAST needs to provide the many laboratories using disk
diffusion for AST with a method with zone diameter correlates for the European breakpoints. The decision to develop a
European disk diffusion test has been taken and work has
commenced. It will be based on Mueller-Hinton medium with
an inoculum corresponding to a 0.5 McFarland standard. It is
our intention to provide zone diameter correlates for European clinical breakpoints during 2009.
Several countries have already started the process of forming national strategies. These processes will be backed by EUCAST,
ESCMID and ECDC. It is in the interest of all to have a coherent
European plan to guarantee that we all mean one and the same
thing when we proclaim a particular microorganism susceptibility or resistance to an antimicrobial drug.
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tion of his outstanding achievements in the field of pathogenesis, diagnosis and treatment of fungal infections. Title of his
award lecture: Antifungal pharmacokinetics and pharmacodynamics: the optimisation of antifungal therapy for immunocompromised patients
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Meeting during the 18th ECCMID in Barcelona on 20 April from
18:15 h – 19:30 h
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Giuseppe Cornaglia welcomed the 82 ESCMID members attending the Assembly 2008. He noted that the minutes of the Assembly 2007 have been published in ESCMID News 2-2007 and that
the invitation and agenda for the Assembly 2008 had been correctly sent out as stated in the Statutes and also published in
ESCMID News 1-2008.
As an introduction to the reports by the individual officers,
Giuseppe Cornaglia made a few general comments about the Society’s major strategic developments. In our own view, ESCMID
now clearly represents the entire scientific and medical community in the field of clinical microbiology and infectious diseases
in Europe. At the same we plan to pay more attention to our
membership by increasing the direct benefits for ESCMID members.
During the reporting period, the composition of the Executive
Committee changed: Hélène Aubry-Damon, Paris, FR, resigned
from her position as Professional Affairs Officer in Clinical
Microbiology in July 2007; she was replaced by Gunnar Kahlmeter, Vaxjo, SE, who was co-opted as a new member to the Executive Committee. For the changes of the CMI Editors see item
10 below. Pentti Huovinen will be the 19th ECCMID 2009 President; he joined the Executive Committee as an ad hoc member
at the day of the Assembly, while Bernhard Ruf, 17th ECCMID
President, left the Committee at the end of 2007.
A Commission for Equal Opportunities was founded to sensitize our organization about a proper balance about gender, geographical area or field of expertise. A first report will be presented at the next Assembly in 2009.
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Javier Garau presented the current membership figures. As of
end 2007, ESCMID had 3’549 regular members, 500 more than
one year ago. Interestingly, this increase in membership is a consistent trend in almost all countries. The best-represented country is still the UK with 263 members, followed by Germany
(225) and the Netherlands (210). Currently 52 societies are affiliated with ESCMID.
The age distribution shows that 60% of our membership is
between 33 and 52 years old, with a sharp decline in the number
of younger or older members.
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Hartmut Lode, DE, asked whether ESCMID considers introducing a joint membership between national societies and ESCMID.
Javier Garau responded that our approach is the affiliation of national societies. We already represent about 20’000 clinical
microbiology and infectious diseases specialists across Europe.
Roger Finch, UK, referred to the encouraging increase in members and suggested running a survey among new members about
the reason for joining ESCMID. Javier Garau agreed and speculated that the increase of ECCMID participants also helps
ESCMID to grow due to the combined registration.
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Ragnar Norrby, Chair of the ESCMID Awards Subcommittee,
first referred to the new programme of training fellowships and
research grants with substantially increased funding in 2008
compared to previous years. The list of recipients thus grew considerably. He had the pleasure to first introduce the ESCMID
Awardees and then the recipients of a grant and a fellowship:
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- Pentti Olavi Huovinen, born 1956 in Helsinki, Finland; MD,
PhD, Professor and Director of the Department of Bacterial
and Infl ammatory Diseases at the National Public Health Institute (KTL), Finland, in recognition of his outstanding contributions to understanding antibiotic resistance, especially
resistance towards macrolides. Title of his award lecture: Microbes and man; from unexpected to unknown
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B^XgdW^dad\nVcY>c[ZXi^djh9^hZVhZh
- Sylvain Brisse, born 1968 in Sète (Hérault), France; PhD, Research scientist at the Unit for Biodiversity of Emerging Bacterial Pathogens at the Institut Pasteur in Paris, in recognition
of his outstanding achievements in the fieldmicrobial phylogenomics, population genetics and epidemiological typing. Title of his award lecture: Diversity and virulence in microbial
pathogens: an evolutionary perspective
- William Hope, born 1969 in Alice Springs, Australia; MBBS,
FRACP, FRCPA, PhD, Senior Research Fellow in Department of Medicine at the University of Manchester, in recogni-
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- Ivan Nikolaev Ivanov, born 1978 in Sofia, Bulgaria; researcher at the National Reference Centre for Diagnosis and Control
of Nosocomial Infections, Sofia, in recognition of his outstanding contribution to improving PCR assays for rapid detection and typing of microbial DNA in clinical and environmental samples
:H8B>9GZhZVgX]<gVcih
- Richard M. Anthony
Royal Tropic Institute, KIT Biomedical Research, Amsterdam, The Netherlands
Project: The effect of sequential acquisition of mutations associated with resistance to the primary drugs of M. tuberculosis in vitro
- Máire Begley
Department of Microbiology and Alimentary Pharmabiotic
Centre, University College Cork, Cork, Ireland
Project: Bile as an environmental cue for the regulation of
Listeria monocytogenes virulence-associated characteristics
- Frank Breinig
Department of Applied Molecular Biology, Saarland University, Saarbrücken, Germany
Project: Recombinant yeast as novel mucosal live vaccine
- Geraldine Canny
Mucosal Immunity Laboratory, Central University Hospital
of Vaud, Lausanne, Switzerland
Project: The role of bactericidal permeability increasing protein (BPI) in intestinal infl ammation and infection
- Marie Hallin
Service de Microbiologie Hôpital Erasme, Brussels, Belgium
Project: Exploration of resistance and virulence factors harboured by methicillin-resistant S. aureus of animal and human origin
- Christine Imbert
Faculty of Medicine and Pharmacy, University of Poitiers,
Poitiers, France
Project: Isolation and characterisation the modulating factor
responsible for the Candida albicans biofilm inhibition
- Lucia Pallecchi
Department of Molecular Biology, University of Siena, Siena, Italy
Project: Mechanisms of acquired antibiotic resistance in bacteria from very remote human communities with minimal antibiotic exposure
- Spyros Pournaras
Department of Microbiology, University Hospital of Larissa,
Larissa, Greece
Project: Clinical impact and molecular analysis of linezolidand vancomycin-resistant Enterococcus faecium (VRE) clinical strains from Greece
- Dóra Szabó
Institute of Medical Microbiology, Semmelweis University,
Budapest, Hungary
Project: Molecular mechanisms and epidemiology of the qui-
nolone resistance in Gram-negative nosocomial bacteria
- Martin Sundqvist
Department of Clinical Microbiology, Central Hospital, Vaxjo, Sweden
Project: Clonal analysis of uropathogenic Escherichia coli to
trace bacterial population changes in response to a large scale
antibiotic intervention study in the community
- Pierre Tattevin
Infectious Diseases and ICU, Pontchaillou University Hospital, Rennes, France
Project: Streptococcus and Enterococcus sp. isolated from
blood culture and/or valves in patients with infective endocarditis: molecular epidemiology and comprehensive susceptibility testing
- Alma C. van de Pol
Department of Virology, University Medical Center Utrecht,
The Netherlands
Project: Is the viral load of respiratory viruses associated with
the severity of respiratory symptoms in young children with
lower respiratory tract infections at the paediatric intensive
care unit?
- Willem van Schaik
Department of Medical Microbiology, University Medical
Center Utrecht, Utrecht, The Netherlands
Project: Functional genomics of hospital-acquired Enterococcus faecium
- Anne Vergison
Paediatric Infectious Diseases Department, Université Libre
de Bruxelles, Brussels, Belgium
Project: Evolution of Streptococcus pneumoniae epidemology
in Belgian children
:H8B>9IgV^c^c\;Zaadlh]^eh
- Esther Heikens
University Medical Center Utrecht, The Netherlands
- Christoph Steininger
Medical University of Vienna, Austria
- Carolina Berglund
Orebro University Hospital, Sweden
- Didier Hocquet
University Hospital, Besancon, France
- Zornitsa Valentinova Mladenova
National Center of Infectious and Parasitic Diseases, Sofia,
Bulgaria
- Ihab Habib
Ghent University, Belgium
- Eveline Snelders
Radboud University Nijmegen, The Netherlands
- Sabeena Ahmed
International Centre for Diarrhoeal Disease Research, Dhaka,
Bangladesh
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Elisabeth Nagy pointed out that our independent auditor from
BDO, Freiburg, DE, has examined the annual accounts 2006 and
2007 and recommends approval without any objection. For the
first time an Assembly can thus approve the accounts of the preceding year. The treasurer further stated that there are no tax arrears of payments and that the non-profit status of the Society
has never been contested. She then presented the final operational results for 2006 and 2007 (Tables 1 and 2) and the balance
sheets for 2006 and 2007 (Tables 3 and 4).
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Operating results 2006
Expenses
Executive Office
-200’223
Membership fees
Membership services
-95’380
ECCMID & other
scientific activities
Executive & other
committees
-66’542
Publications (incl. website)
-231’129
Educational &
scientific activities
-197’785
Awards,
grants & fellowships
-69’790
Professional & public
affairs (incl. ECDC, EU,
EUCAST, GRACE)
-94’476
Taxes
-13’671
Total expenses
Operating results 2007
Income
-968’996
CMI & other journals
Awards
Other (incl. interest
and donations)
Total income
Result
Expenses
38’247
2’324’825
148’234
28’000
128’305
2’667’611
1’698’615
Table 1. Operating results 2006
Income
Executive Office
-434’547
Membership fees
Membership services
-143’439
ECCMID & other
scientific activities
Executive Committee
-88’166
Publications (incl.
subc’tee and website)
-395’894
Educational &
scientific activities
(incl subc’tees)
-284’204
Awards,
grants & fellowships
-67’400
Professional &
public affairs (incl.
ECDC, EU, EUCAST,
GRACE, UEMS, subc’tee)
CMI & other journals
Awards
82’555
1’263’931
202’696
28’000
-274’148
Professional &
public affairs (incl
EUCAST, IPSE, GRACE,
UEMS)
156’029
Other
-20’830
Other (incl. interest
and donations)
181’201
Taxes
2’208
-1’706’420
Total expenses
Total income
Result
1’914’412
207’992
Table 2. Operating results 2007
Balance sheet 2006
Assets
Liabilities
Fixed assets
793’597
Circulating assets:
– Goods
– Cash
– Bank
1’523
381
2’290’811
Accounts receivable
1’383’100
Prepaid expenses
Balance total
Balance sheet 2007
600
4’470’027
Profit carried forward
Free reserve
Provisions
Assets
2’240’228
495’904
19’500
Circulating assets:
– Goods
– Cash
– Bank
Accounts payable
316’784
Accounts receivable
Accrued income
194’900
Prepaid expenses
Balance total
Liabilities
Fixed assets
4’347
0
487
3’815’509
732’057
7’622
Profit carried forward
3’450’931
Free reserve
Provision
695’904
20’085
Accounts payable
229’693
Accrued income
163’409
4’470’027
Balance total
Profit carried forward plus
free reserve as of 31 Dec 2006
3’938’843
Profit carried forward plus
free reserve as of 31 Dec 2007
4’146’835
Profit carried forward as of 31 Dec 2005
2’240’228
Profit carried as of 31 Dec 2006
3’938’843
Result 2006
1’698’615
Result 2007
4’560’022
Balance total
4’560’022
207’992
Table 3. Balance sheet as of 31 Dec 2006
Table 4. Balance sheet as of 31 Dec 2007
Based on the excellent financial situation of ESCMID, the
Executive Committee increased spending in 2007 in most areas
to the benefit of the membership. In addition, the free reserve
was increased by EUR 200’000 to EUR 695’904. Elisabeth Nagy
pointed out that the budget 2008 foresees further increases in the
funding of research grants, training fellowships, medical guideline development and educational and scientific activities.
wondered about the German authorities accepting revenues of
several Mio EUR on the Society’s bank accounts. Giuseppe Cornaglia answered that indeed our assets should not further increase. Peter Schoch confirmed that we will strive in future for
balanced budgets with expenses equalling income. Our current
assets allow ESCMID to survive two years without revenues;
this is the amount accepted by the authorities for a non-profit
society.
Questions from the floor:
Pramod Shah, Frankfurt, Germany, congratulated ESCMID on
these results and asked whether indeed ESCMID spends more
than EUR 0.5 Mio for administration. Elisabeth Nagy confirmed
this figure and mentioned that currently seven people are employed in the Executive Offices to manage and support the increasing number of activities of the Society. Pramod Shah suggested that the financial accounts be published on the ESCMID
website. Elisabeth Nagy referred to the minutes, which will include all figures and be published as in previous years in
ESCMID News and on the website. Hartmut Lode, Berlin, DE,
6
ESCMID NEWS 02/2008
SOCIETY
5 Approval of the accounts (vote)
Giuseppe Cornaglia asked for sequential hand votes of approval
of the financial reports for 2006 and 2007. Both were approved
unanimously.
6 Report of the Education Officer
In 2007 the following educational activities were held as reported by Murat Akova:
i) 6th ESCMID School, Suceava, Romania, 1 – 6 July 2007,
organized by the ESCMID Education Committee, directed
by Roxana Filip and Corina Stanescu, Suceava. A record
number of 53 students attended from 18 different countries.
ii) Nine postgraduate courses (PGC) were held under the auspices of and supported by ESCMID:
1 Conventional and Rapid Diagnostic Approaches to RTI in
Support of More Targeted Therapy (GRACE PGC, organized with ERS)
30 – 31 March 2007, Munich, Germany
2 Practical and Theoretical Course on Bacterial Molecular
Typing (organized with ESGEM)
29 April – 4 May 2007, Oeiras, Portugal
3 Role of Anaerobic Bacteria in Infections: Diagnostics, Antibiotic Resistance and Therapeutic Options (organized with
ESGARAB and ESGCD)
4 June 2007, Szeged, Hungary
4 A Modern Approach to the Management of Sexually Transmitted Diseases (organized with IACMAC)
7 – 8 September 2007, Saint Petersburg, Russia
5 From Cough to Asthma: the Role of Infection
(GRACE PGC, organized with ERS)
15 September 2007, Stockholm, Sweden
6 LRTI – Current Concepts in Pathogenesis, Microbiology,
Epidemiology and Economic Impact (GRACE Workshop,
organized with ERS)
22 – 24 October 2007, Prague, Czech Republic
7 Bacterial Adaptation Mechanisms: Biofilms, Hypermutability and Antibiotic Resistance (organized with ESGB)
7 November 2007, Palma de Mallorca, Spain
8 Update on Invasive Fungal Infections: Epidemiology, Diagnosis and Antifungal Susceptibility Testing (organized with
EFISG)
8 – 9 November 2007, Innsbruck, Austria
9 ESCMID-SHEA Training Course in Hospital Epidemiology
(organized with SHEA)
10 –13 November 2007, Prague, Czech Republic
iii) During the 17th ECCMID 2007 in Munich, in addition to 17
meet-the-expert sessions, eleven pre-ECCMID educational
workshops were organized in collaboration with ESCMID
Study Groups or other organizations:
1 Non-invasive tests for diagnosis of Helicobacter pylori infection (organized with EHSG)
2 Diagnosis and follow-up in lower respiratory tract infections
(organized with ESPRIT)
3 The burden of Toxoplasma gondii infections: congenital or
acquired? (organized with ESGT/ESGCP)
4 Infection control – starting from zero
(organized with ESGNI)
5 Ways to improve the quality of antimicrobial therapy (organized with ESGAP)
6 Interaction of bacterial biofilms with defense mechanisms
and foreign bodies (organized with ESGB)
7 Management of chronic fungal diseases (organized with
EFISG)
8 Case studies in clinical virology: laboratory choices and
challenges in detecting and monitoring viral infections (organized with ASM)
9 Pharmacokinetics and pharmacodynamics of anti-infective
agents (organized with ISAP)
10 Healthcare-associated infection and antimicrobial resistance
– a challenge for organization and management (organized
with IPSE)
11
Infections in the intensive care unit (organized with the ISC
Working Group, “Infections in the ICU”)
According to Murat Akova a standardized course evaluation
form and reporting system was introduced in the reporting period. This will in future allow us to better tailor courses and workshops to the needs of our members.
7/8
Report of the Professional Affairs Officers for Clinical
Microbiology and Infectious Diseases
Due to considerable overlap of their portfolios, Robert Read and
Gunnar Kahlmeter, the Professional Affairs Officers for Infectious Diseases and Clinical Microbiology, respectively, teamed
up in presenting their reports.
Robert Read first referred to the formation of a Professional
Affairs Subcommittee (PAS) with some 19 members from both
specialties. Its prime goal is to advise the Executive and guide
decision making in Professional Affairs. Two meetings took
place so far, which focused, among others, on the preparation of
a Professional Affairs Workshop „Moving Forward in Cooperation“ taking place from 9 – 10 October 2008 in Rome.
He then gave an overview of the ongoing medical guideline
developments:
- International guidelines for management of severe sepsis and
septic shock (in cooperation with the Surving Sepsis Campaign, published in Crit. Care Med. 2008; 36:296–327)
- Guidelines on the diagnosis and management of Clostridium
difficile-associated disease (ESCMID guidelines, ongoing,
led by Ed Kuijpers, Leiden, NL)
- Lower respiratory tract infection (ongoing, in cooperation
with ERS)
- Endocarditis (ongoing, in cooperation with ECS)
- Catheter-related urinary tract infection (ongoing, in cooperation with IDSA)
- Urinary Tract Infection (ongoing, in cooperation with IDSA)
Robert Read encouraged the members to propose suitable topics
for the development of ESCMID guidelines. Suggestions of excellent national guidelines, which can serve as templates for European “expansion”, and of experts willing to lead a writing
committee are also welcome.
Gunnar Kahlmeter then presented the “road map” towards the
compilation of a “White Book” on Clinical Microbiology and
Infectious Diseases. It is based on an online questionnaire to be
filled in by national representatives. The database containing detailed information about the organizational basis of our specialties in Europe will eventually be published in ESCMID News
and on the internet.
Another project being implemented is related to facilitating
international exchange of ESCMID members: Departments of
Clinical Microbiology or Infectious Diseases can apply for the
status of an “ESCMID Collaborative Centre” and publish their
profile on the ESCMID website. This entitles them to participate
in an “ESCMID Observership Programme” by receiving individuals for one day to one month for professional exchange. Observerships will be reserved for ESCMID members and be funded by ESCMID.
9 Report of the Scientific Affairs Officer
Jordi Vila reported that there were still 16 Study Groups operating under the auspices of ESCMID in the reporting period as one
year ago. The only change relates to the “expansion” of ESGT to
ESGCP, i.e. from “toxoplasmosis” to “clinical parasitology”.
The activities of the Study Groups were reviewed by and dis-
ESCMID NEWS 02/2008
SOCIETY
7
cussed with the members of the Scientific Advisory Subcommittee. The ESCMID Study Groups published 17 papers, submitted
29 abstracts to conferences and congresses, (co-) organized seven scientific meetings, 19 educational courses or workshops and
were involved in 15 research projects. Jordi Vila acknowledged
the increased scientific output of the Study Groups and thanked
them for their commitment.
In the past year ESCMID was involved in the organization of
six scientific conferences:
1 14th International Workshop on Campylobacter, Helicobacter
and Related Organisms (co-organized by EHSG)
2 – 5 September 2007, Rotterdam, The Netherlands
2 FEMS/ESCMID Conference on Streptococcus pneumoniae
7 – 11 October 2007, Villars-sur-Ollon, Switzerland
3 European Meeting on Molecular Diagnostics (co-organized
by ESGMD)
18 – 19 October 2007, Scheveningen, The Netherlands
4 International Symposium: Bacterial Adaptation Mechanisms:
Biofilms, Hypermutability and Antibiotic Resistance (organized by ESGB)
8 – 9 November 2007, Palma de Mallorca, Spain
5 ESCMID Conference on Pseudomonas aeruginosa
18 – 20 November 2007, Barcelona, Spain
6 European Consensus Conference on the Management of
MRSA
13 – 14 December 2007, Ljubljana, Slovenia
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As Chair of the Publication Subcommittee Ragnar Norrby reported another successful year for CMI. In 2007, twelve regular
issues were published, which comprised 1’243 pages, plus four
supplements. The impact factor increased to 3.25, thus ranking
CMI among the leading journals publishing original research in
its field. The time from acceptance to publication remained at a
low of 4 to 5 months. Most pleasing was the usual strong increase of downloads, this year almost exponential, which indicates an increasing readership of our journal.
Kevin Towner, having reached the end of his term, stepped
down from office as Editor-in-Chief of CMI at the end of March
2008. Ragnar Norrby thanked him for his achievements. The
new Editor-in-Chief, in charge of new submissions since 1 April
2008, is Didier Raoult, Marseille, FR.
Another change took place in the editorial office for the CMI
supplements. Carl Erik Nord, who had several functions in the
Society since 1986, resigned from being Supplements Editor and
was replaced by George Schmid, Geneva, CH. Ragnar Norrby
also thanked him for his many contributions to the Society.
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Giuseppe Cornaglia congratulated Fernando Baquero, the President of the 18th ECCMID, on an outstanding congress. Since
Fernando Baquero was unable to attend, Peter Schoch presented
the numbers of this year’s ECCMID, which breaks all records:
- Number of participants: 9’585, thereof: 7’964 delegates, 405
accompanying persons, 1’216 exhibitors’ personnel
- Best countries: ES, UK, GR, US, FR, DE, IT
- Exhibition: 106 exhibiting companies, 2893 m2 net area
- Press: 84 registered journalists, ten press releases.
The contact time during keynote lectures, symposia, educational workshops, meet-the-expert and oral sessions increased to
238 hours.
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Andreas Voss was most pleased by the strong response of the
scientific community to the call to submit abstracts of their original research. ECCMID has received a record number of 3’655
abstracts from 88 different countries. A total of 233 reviewers
conducted a blind review the abstracts, of which 36% were rejected. This high rejection rate has certainly contributed to the
high quality of this year’s poster sessions. The most popular topics were resistance surveillance, non-molecular diagnostic laboratory methods, public health and community-acquired infections, and fungal infections.
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fail to be elected may not be nominated again for the immediate following term.
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Andrew Ullmann, Mainz, DE and Pramod Shah, Frankfurt, DE,
both proposed to drop the latter requirement in order to give full
competence to the membership to nominate whomever they
want. Giuseppe Cornaglia defended the official proposal. It seeks
a balance between strengthening the democratic rights of the
membership and – at the same time – foresees measures to prevent repetitive lobbying campaigns for individual candidates.
The changes of Statutes related to the nominating rights by
the membership were approved by a vast majority with two votes
against the proposal and five abstentions.
The total number of speakers and chairs was 849. They came
from 46 different countries (see Figure 2).
Andreas Voss then acknowledged the members of the 18th
ECCMID Programme Committee, which he called his “dream
team”, for compiling such a superb scientific programme.
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Giuseppe Cornaglia asked for a hand vote to approve the actions
of the Executive Committee in 2007 and to grant discharge to
the Executive Committee. Both were unanimously approved and
granted, respectively.
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The proposed amendments of the Statutes fall into two categories as pointed out by Giuseppe Cornaglia:
i) The current Statutes do not foresee a specific responsibility
for the President-elect, for which reason it is proposed to
unify this position with that of the Secretary General. This
makes sense since the latter position should be held by an
experienced person, which is certainly the case for the President-elect. This corresponding change of the Statutes, § 4
Organization, was unanimously approved.
ii) So far, the candidates for the Executive Committee to be put
on the ballot sheet were selected by a nominating committee. In order to strengthen the democratic basis of our Society and to give more infl uence to our membership, it is proposed, following a proposal from Pramod Shah, Frankfurt,
DE, that candidates be put on the ballot if at least 30 members support the nomination with their signatures. At least
15 supporting members must come from countries other
than the country of the nominated candidate. Nominees who
Giuseppe Cornaglia
ESCMID President
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Giuseppe Cornaglia informed the Assembly that ESCMID has
again concluded a Memorandum of Understanding with the International Society of Chemotherapy (ISC) concerning the conduct of a joint congress ECCMID / ICC in 2011. It will be the
21st ECCMID and the 27th ICC and be held in Milan, Italy.
Comment from the fl oor: Kurt Naber, Straubing, DE, confirmed as current ISC President his enthusiasm for the Memorandum of Understanding. The basis for the continued cooperation is the huge success of the joint 17th ECCMID/25th ICC
2007 in Munich.
There was no further request to speak.
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Giuseppe Cornaglia thanked the members for attending. He adjourned the meeting at 19:30 h.
Basel, 7 July 2008
Javier Garau
ESCMID Secretary General
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Peter Schoch
Managing Director
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This article is the first issue of short column entitled From the Executive to appear from now on
regularly in ESCMID News to inform our members about developments and initiatives within our
Society.
oped by Gunnar Kahlmeter for funding EUCAST by the EU. It is entitled Standardisation
of antimicrobial breakpoints susceptibility tests
for improving surveillance at the European level and runs over three years.
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- Preparations have started for the election of two
new members to the Executive Committee for
the term 2009 – 2013. Members of good standing since at least one year have been asked to
nominated candidates. Members will be asked
to cast their vote in December 2008 through the
Internet.
- The company Association Global Services
(AGS) has been asked by Giuseppe Cornaglia
for a strategic assessment of ESCMID’s position, legal status and governance. The report
will form the basis for planning the future development of ESCMID.
- The ESCMID Bylaws have been recently extensively revised by the Executive under the supervision of the Secretary General, Javier Garau.
For the full new version see the ESCMID website.
- This year’s Assembly of Members took place on
20 April 2008 in Barcelona. The minutes are
published on the ESCMID website and in this
issue of ESCMID News. They include the detailed reports by all Officers including that of
the treasurer Elisabeth Nagy, which demonstrates the financial health of our Society.
- Peter Schoch has announced his resignation
from the position as ESCMID Managing Director. Peter Cologna will be the new Managing
Director as of 1 November 2008.
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- On 25 July 2008 an expert meeting on Chikungunya organized by Jordi Vila took place in
Barcelona under the auspices of ESCMID and
ASM. It addressed epidemiological, diagnostic
and treatment aspects and was recorded for dissemination through the ESCMID and ASM
websites.
- A proposal for a joint ESCMID/bioMérieux
grant for young scientists from East Central and
Eastern Europe for research in the field of diagnostic microbiology has been approved. For details see the ESCMID website.
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- In July and August 2008 an electronic survey on
Clinical Microbiology and Infectious Diseases
will be conducted among national societies affiliated with ESCMID. The data will eventually
be published as a European CM & ID White
Book on the ESCMID website and provide
transparency to the organizational structures of
our specialties across Europe.
- In response to a recent call by the European
CDC, ESCMID has submitted a proposal devel-
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- As a basis for planning ESCMID’s educational
activities, a coherent strategy defining objectives, priorities and procedures was developed
by Murat Akova. Yearly proposals for postgraduate courses and workshops are sought from
ESCMID Study Groups and affiliated societies
and must be received by the end of June of the
preceding year. The plan foresees a maximum
of twelve educational events per year (in addition to the Summer School and educational
workshops at ECCMIDs) and strives for scientific and geographical balance of our educational offer. Additional measures will be taken to
optimise the educational impact through advertisement, by providing financial support and by
making slides available to ESCMID members
through the Internet.
Peter Schoch
for the Executive Committee
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Results of the Opinion Poll
18th ECCMID 2008 Barcelona
Andreas Voss, ECCMID Programme Director
This year 7’964 delegates attended the ECCMID 2008 in Barcelona, an increase of 1’575 delegates (25%) compared to the joint
ECCMID/ICC last year. Hence, the number of congress participants still continues its steady increase with a few dips in the
trend since the first ECCM in 1983 with 850 participants (Figure
1)!
Figure 1. Number of delegates and received abstracts
for the ECCMIDs since 1983
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participants concerning specific content missed at ECCMID.
Among the few mentioned were virology and vaccinology, two
topics which will be given more attention next year at the
ECCMID in Helsinki.
Along with the increasing number of participants over the
years, the scientific programme was also growing and offered in
2008 more topic coverage than ever with a total of 238 hours of
contact during keynote lectures, symposia, oral and meet-theexpert sessions and educational workshops. Eighty-two percent
of responders indicated that the programme met their expectations of getting the latest scientific information in their field
(Figure 2). Naturally a programme with many simultaneous sessions has the disadvantage that individuals cannot attend all the
sessions they would like. The possibility of capturing some or all
sessions to be made available after the congress is being considered again for next year.
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Figure 2.
5. Did the scientific programme meet your expectations of
getting the latest scientific information in your field?
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yes
no
partially
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We are pleased to report that most participants found the poster
session quality either better or the same as in previous years
(Figure 3). The abstract rejection rate, which was 36%, will not
be increased in the near future as a balance seems to have been
struck between quality and giving scientists the opportunity to
present their work.
Some participants complained that there was too little space
between the poster rows to ac-commodate ad hoc discussions
with presenters without interfering with visitors to adjacent posters. We will improve this in future by planning for larger poster
areas. A number of participants also would like poster sessions
to be longer than one hour so as to be able to see more of them
per session. This option will be carefully evaluated for next
year.
improved
worsened
no change
65.6%
2.1%
32.3%
743
24
366
During breaks, when participants crowded into the halls and foyers, seating opportunities and tables were found to be scarce.
This will be kept in mind when setting up the facilities for the
ECCMID conference centre next year in Helsinki. On a positive
note, most lecture halls seem to have been large enough to accommodate the delegates who wanted to attend a given session.
As in previous years there were again comments made about
an insufficient number of catering facilities within the congress
building as well as a low food quality offered. We are almost
sure that this will not be a problem next year. The Conference
Centre in Helsinki has many restaurants and food corners of
good quality which render special measures, such as distributing
lunch boxes, unnecessary.
This year some participants missed hotel shuttles to the congress centre, which were available in some previous years when
the congress centre was less accessible by public transportation.
The decision as to whether to provide shuttle service is dependent on the centre’s accessibility via public transportation.
Finally, we would like to thank all of you who responded to
the opinion poll. Your feedback is invaluable to improving upon
the congress. We look forward to seeing you in Helsinki from
the 16 – 19 May 2008.
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We are happy to report that 1’133 participants filled out the online opinion poll for this year’s ECCMID. Overall, the vast majority of the respondents was highly satisfied with the congress.
Responses from all questions, except for those requiring a written response, can be found on the ESCMID website, “Opinion
Poll”.
As was the case last year most respondents (83%) found that
there was a good balance of the scientific programme between
basic science and practical aspects. It is also encouraging that
this year a much smaller number of suggestions was made by
81.6%
3.1%
15.3%
Figure 3.
7. The quality of the poster sessions is a constant concern. This
year we have significantly increased the abstract rejection rate to
36%. How do you rate the quality of the poster sessions in 2008?
12
ESCMID NEWS 02/2008
SOCIETY
ESCMID NEWS 02/2008
SOCIETY
13
The First European Day of Fighting Infection
The First European Day of Fighting Infection held
on 23 April 2008 in Barcelona was a great success
and it is planned to be the first of many to come. If
you were unable to attend this year, you can find
the Powerpoint presentations on the ESCMID
website (www.escmid.org/presentations). More information about future renditions will be available
on the ESCMID website at a later date.
The ESCMID Executive Committee
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Alasdair Geddes speaking about quarantine and lazarettes from the
Middle Ages through the 20th century
Group photo of speakers (l. to r.): Raul Isturiz, Fernando Baquero,
Didier Raoult, Giuseppe Cornaglia, Franco Cardini, Javier Garau,
Alasdair Geddes, Sherwood Gorbach
14
ESCMID NEWS 02/2008
SOCIETY
Javier Garau gave an interesting talk about the social and cultural
influence of St. George, his importance to Western culture and his
relation to the Day of Fighting Infection
ESCMID NEWS 02/2008
SOCIETY
15
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Following the recent changes in editorial responsibility the
guidelines for authors and instructions for online submission to
Clinical Microbiology and Infection have been revised. In particular, please see the sections below concerning Manuscript
Categories and Authorship.
Amendments and procedures that are frequently misunderstood are underlined.
The guidelines, which will be updated periodically, are available on the ESCMID website (www.escmid.org/CMI).
Ê Clinical Microbiology and Infection (CMI), the official publication of the European Society of Clinical Microbiology and Infectious Diseases, was initiated in 1995 and publishes manuscripts presenting the results of original research in clinical
microbiology, infectious diseases, virology and parasitology, including immunology and epidemiology as related to these fields.
The journal also publishes invited editorials and reviews, as well
as guidelines and position papers originating from ESCMID
Study Groups and ESCMID-sponsored conferences.
Information and Guidelines for Authors
18th ECCMID 2008 Barcelona
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Do not send a scanned version of the submission document
electronically and do not send the document by fax; please send
by post to the address below:
Judith Crane, CMI Editorial Office, 39 Quai de Grenelle,
75015 Paris, France
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5 – 10 key words
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A manuscript category may change during the course of
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ESCMID European Council Meeting
Minutes
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1 Approval of the Minutes of the European Council Meetings
in 2007
The minutes from the European Council meetings were approved
with the following amendments:
1) Minutes European Council meeting April 2007 in Munich:
item 6: …Bernard Maillet, UEMS Secretary General, pointed
out that one-third of the UEMS member countries must recognize a specialty in their home territories to warrant the formation
of a new UEMS Section.
2) Minutes Extraordinary European Council meeting December 2007 in Rome: item 4: …Professional Affairs Workshop
2008 which will be organized from 9 – 10 October 2008 in
Rome.
2 ESCMID 2007 – 2008 progress reports: matters of
relevance for the European Council
Javier Garau presented an update on the affiliation process. Up
to now 53 specialists societies have signed an affiliation agreement with ESCMID. There is still more to do since the estimated
potential is about 80 societies with some 30’000 members. Javier Garau summarized the activities of ESCMID in the fields of
science and education. He pointed out that ESCMID maintains
cooperative partnerships with many professional societies and
that ESCMID is currently preparing Memorandums of Understanding with ASM, CMA, IDSA and ISID. Furthermore,
ESCMID has entered joint cooperative educational and scientific
ventures with several other international societies, such as
- with ISC (17th ECCMID / 25th ICC, 31 March – 3 April 2007
in Munich and 21st ECCMID/27th ICC, 7 – 10 May 2011 in
Milan)
- with FEMS (annual jointly organized scientific conference on
New Frontiers in Microbiology and Infection)
- with ERS (the educational platform of GRACE).
In future more emphasis shall be put on strengthening the cooperation with affiliated societies across Europe in educational,
scientific and professional affairs.
CMI Editorial meeting, 14th ECCMID 2004
Kevin Towner has now completed his five-year term of office as Editor-in-Chief. Most
of the Editors who served during his term have accepted to remain as members of the
Editorial Board or as Associate Editors along with the new Editors invited by his
successor as Editor-in-Chief, Didier Raoult. As in the past, editorial meetings will be
held annually during ECCMID.
20
ESCMID NEWS 02/2008
SOCIETY
3 Advanced planning of the Professional Affairs Workshop,
9 – 10 October 2008, Rome
Robert Read outlined the programme of the ESCMID Workshop
on Professional Affairs in Clinical Microbiology and Infectious
Diseases. He encouraged active participation of all affiliated societies with the hope that at least one representative of each affiliated society will participate in the workshop. The registration
fees are very moderate and ESCMID supports the workshop by
providing attendance grants for a large number of young attendees.
4 Road Map to a White Book of Clinical Microbiology and
Infectious Diseases in Europe
Gunnar Kahlmeter presented the “road map” of a White Book of
Clinical Microbiology and Infectious Diseases. It is based on an
online questionnaire to be filled in by national representatives.
The Professional Affairs Officers have made every effort to make
the questionnaire relevant by consulting specialists in many
countries. The questionnaire will be sent to the affiliated societies after a final review by the Professional Affairs Subcommittee and UEMS representatives. The final dataset containing detailed information about the organizational basis of our specialties
in Europe will eventually be published in ESCMID News and on
the Internet.
5 Other Professional Opportunities
Robert Read gave an overview of the recent medical guideline
developments:
- International guidelines for management of severe sepsis and
septic shock (in cooperation with the Surving Sepsis Campaign, published in Crit. Care Med. 2008; 36:296–327)
- Guidelines on the diagnosis and management of Clostridium
difficile-associated disease (ESCMID guidelines, ongoing,
led by Ed Kuijpers, Leiden, Netherlands)
- Lower respiratory tract infection (ongoing, in cooperation
with ERS)
- Endocarditis (ongoing, in cooperation with ECS)
- Catheter-related urinary tract infection (ongoing, in cooperation with IDSA)
- Urinary tract infection (ongoing, in cooperation with IDSA).
Gunnar Kahlmeter and Robert Read then presented another
project which will be implemented to facilitate international exchange of ESCMID members: Departments of Clinical Microbiology or Infectious Diseases can apply for the status of an
ESCMID Collaborative Centre and publish their profile on the
ESCMID website. This entitles them to participate in an
ESCMID Observership Programme by hosting individuals for
one day to one month for professional exchange. The aim is not
only to attract trainees but also senior clinical microbiologists
and infectious disease physicians.
Mario Poljak raising a question
ESCMID NEWS 02/2008
PROFESSIONAL AFFAIRS
21
Comments from the floor:
Mario Poljak (Slovenia): Does ESCMID plan any cooperation
with ECDC in guideline development? Ragnar Norrby replied
that ESCMID is represented in the ECDC Advisory Forum
through Elisabeth Nagy and that there is strong link between
ESCMID and ECDC. We will certainly avoid any duplication
and seek cooperation with ECDC if this is justified, e.g. in the
field of community- and hospital-acquired MRSA infection and
the harmonization of breakpoints for resistant bacteria.
Helle Krogh Johansen (Denmark): Are the application forms
for ESCMID Observerships already available on the website?
Gunnar Kahlmeter responded that the Professional Affairs Subcommittee members will first review the application forms for
suggestions and improvements before they will be put online.
The project, which also includes the establishment of ESCMID
Collaborative Centres, will presumably start by the end of this
year.
Gijs Ruijs (The Netherlands): The concept of an observership
is interesting for the individual. Is there also a spin-off for the
Society? Gunnar Kahlmeter and Robert Read responded that the
aim of the programme is to foster mobility and career options for
trainees and established researchers. Serving its members is justification enough. But after completing a visit, submission of a
short report is required for publication on the ESCMID website.
6 UEMS: towards an autonomous Microbiology Section
John Degener, Chair of the Microbiology Commission, informed
the participants that UEMS voted at its last meeting in Brussels
(19 April 2008) for an independent UEMS Section of Medical
Microbiology. He shortly summarized the history of this long
decision process that finally ended favourably. The first meeting
of the new UEMS Section of Medical Microbiology will be held
on the 21 April 2008 during the 18th ECCMID in Barcelona.
Giuseppe Cornaglia happily thanked John Degener, Elisabeth
Nagy and all representatives in the UEMS Section for their efforts to bring this issue to a successful conclusion.
7 1st European Day for Fighting Infection
On the occasion of its 25th anniversary, ESCMID celebrates the
1st European Day of Fighting Infection with a one-day symposium on 23 April 2008. It will be devoted to the importance of
infections in the past, present and future and their relevance in a
socio-economical context on the daily life on our continent.
Giuseppe Cornaglia invited the representatives of the affiliated
societies to take part in this important event.
ESCMID intends to organize the European Day for Fighting
Infection annually with the aim to strengthen the link between
ESCMID and the national societies and organizations.
ated the European Antibiotic Awareness Day that will be held for
the first time in November this year. Ragnar Norrby confirmed
that the European Antibiotic Awareness Day is an initiative of
the ECDC in close collaboration with other Institutions of the
European Union and the Members States. ECDC only provides
promotional material but no further support. The cost for the
campaign is covered by the Members States’ governments.
Giuseppe Cornaglia added that the European Day for Fighting
Infection will focus on fighting infection only and will not specifically address antibiotic resistance to avoid an overlap with
the ECDC initiative.
8 Election of two EUC members to the Nomination Subcommittee
Ragnar Norrby as chair of the Nomination Subcommittee explained that in preparing for the election to the ESCMID Executive Committee in December 2008, ESCMID should form the
Nomination Subcommittee, which will be responsible to put up
the ballot sheet with valuable candidates. According to the newly
revised Bylaws, this Subcommittee consists of the Past President, two additional members from the ESCMID Executive
Committee and two members elected by the European Council.
The term of office is 2 years. Ragnar Norrby asked the present
representatives of the affiliated societies for proposals of nominees.
The following members volunteered as candidates to serve on
the Nomination Subcommittee:
- Helle Krogh Johansen, Copenhagen, Denmark (microbiologist)
- Mario Poljak, Ljubljana, Slovenia (microbiologist)
- Gijs Ruijs, Zwolle, the Netherlands (microbiologist)
- Jean-Paul Stahl, Grenoble, France (ID specialist)
Ragnar Norrby thanked the candidates and pointed out that the
election of two members will be conducted by email/fax among
all affiliated societies within the next few weeks.
9 Issues raised by the Affiliated Societies
In December 2007, an extraordinary meeting of the European
Council took place. This was in preparation of the ESCMID
Workshop on Professional Affairs. Giuseppe Cornaglia emphasized that this was an exception and that the next official meeting
of the European Council will be the regular meeting during the
19th ECCMID in 2009 in Helsinki.
Giuseppe Cornaglia thanked the participants for their participation and adjourned the meeting at 14:15 h.
Basel, 27 June 2008
Comment from the floor:
John Degener (The Netherlands) mentioned that ECDC has initi-
Giuseppe Cornaglia
ESCMID President
[email protected]
22
ESCMID NEWS 02/2008
Javier Garau
ESCMID Secretary General
[email protected]
PROFESSIONAL AFFAIRS
Karin Werner
ESCMID Professional Affairs Manager
[email protected]
Medical Microbiology Now an Independent Section
European Union of Medical Specialists (UEMS)
John E. Degener, Past convener of the Commission of Medical
Microbiology of the UEMS Section of Medical Biopathology,
Candidate for Dutch Delegate of the UEMS Section of Medical
Microbiology (in formation)
In two previous articles (ESCMID News 2007; issue 2:14 -17
and issue 3: 10-12) it has been explained how the specialty of
Medical Microbiology has been represented by a commission or
subsection of the UEMS Section of Medical Biopathology for
decades. Medical Biopathology is an umbrella for a number of
laboratory-oriented medical specialties. The informal organization of Medical Microbiology under this umbrella is no longer
acceptable in modern Europe, in which the large majority of
countries recognize Medical Microbiology as a full specialty
with a prominent place in medical care and the prevention of
infectious diseases.
Although the criterion for creating a new Section of at least
one third of UEMS member states recognizing the full specialty
was more than met (20 of 27 UEMS members recognize Medical
Microbiology), this act was hampered by reluctance of the Section of Medical Biopathology to allow a split off. This can be
well understood because of the various ways one may look in
Europe at the position of Medical Microbiology in the practice
of laboratory medicine. Members of the so-called polyvalent
commission of the Section of Medical Biopathology argued that
in their specific national situation, a split off would weaken the
profession and would make the practice of laboratory medicine
less efficient from a logistic and financial point of view.
As became clear during long discussions in the meetings of
the Section of Medical Biopathology the arguments against a
split off were not insignificant but a majority of country delegates in the commission of Medical Microbiology still endorsed
the creation of an independent Section. At the UEMS Council
meeting in Bratislava in October 2007, it was decided to let the
country delegates from the national medical associations vote at
the next spring meeting in Brussels in 2008. A condition was
made that the Section of Medical Biopathology and the members
of the commission of Medical Microbiology should seek a way
for future cooperation. Even if the split off would be a fact, a
solution should be found for a position of medical microbiologists in countries which do not fully recognize the specialty.
For a more detailed description of previous events, please see
the above-mentioned ESCMID News articles.
Presently, the new Section of Medical Microbiology finds itself in an interim situation. The Secretary General of the UEMS,
Dr. Bernard Maillet, has sent a request to the medical associations in the UEMS member states to nominate delegates to the
Section, two from each country. The next meeting will take place
in Brussels on 27 September on the premises of UEMS. Apart
from voting for the board members of the Section a follow up
shall be given to the important discussion on the harmonisation
of modern training programmes for our specialty in the EU.
The Section of Medical Biopathology has decided to maintain
a “Division” of Medical Microbiology. The renaming of com-
missions has been proposed by the UEMS Council. The Division
of Medical Microbiology seeks to cover the professional interests of polyvalently trained medical microbiologists and other
specialists in our field in countries where Medical Microbiology
is not or not fully recognized. It will be important to keep close
contact with delegates in this Division, informing them about
training programmes and providing information on the performance of specialist practice. Even if, by directive, free movement
of medical specialists in the EU member countries was possible,
specialties in Europe would be multi-faceted for many years to
come. Mutual understanding shall be of utmost importance to be
able to cooperate and to strengthen the specialty of Medical
Microbiology, regardless of different national backgrounds or
training programmes.
Recent and future highlights in the process of becoming an
independent Section
- 11 – 13 October 2007, UEMS Council meeting, Bratislava: Commission of Microbiology makes plea for an
independent Section. Decision made to let the country
delegates from the national medical associations decide
by a majority vote at the next spring meeting in Brussels
in 2008
- 19 April 2008, UEMS Council Meeting, Brussels: vote
for an independent Section with 22 votes in favour, 2
against and 4 abstentions. Section is to be named “Section of Medical Microbiology”.
- 21 April 2008, during 18th ECCMID, Barcelona: discussion among the Medical Microbiology commission
delegates about the next steps to be taken
- 17 May 2008, Section of Medical Biopathology meeting, Bern: decision made to maintain a “Division” of
Medical Microbiology within the Section of Medical
Biopathology
- 27 September 2008, Section of Medical Microbiology
meeting, UEMS premises, Brussels: vote to be held to
elect the board members of the Section of Medical
Microbiology and a follow up discussion planned on the
harmonization of modern training programmes for the
specialty in the EU
ESCMID NEWS 02/2008
PROFESSIONAL AFFAIRS
23
Moving Forward in Co-operation: Join the
Debate on Our Professional Future
Gunnar Kahlmeter, Professional Affairs Officer,
Clinical Microbiology,
[email protected]
Robert C. Read, Professional Affairs Officer,
Infectious Diseases,
[email protected]
Conditions for speciality training in Clinical
Microbiology and Infectious Diseases in Europe
are veritable minestrone of widely different curricula and organizational requirements.
Pitfalls lie in wait not only for our young and
not-so-young professional members aiming for an
international career, but also for the harmonization
and improvement of microbiological diagnostics,
clinical care and public health in Europe.
The professional structures in which clinical
microbiologists and infectious disease physicians
operate are of great interest to ESCMID, especially
in the areas where European cooperation is needed.
If we cannot achieve complete pan-European harmonization, then at least we can try to understand
completely the situation across our different nations, and identify the problems that we face, at the
individual and national levels as well as internationally. In the year of its 25th anniversary
ESCMID has therefore decided to devote two major initiatives to advancing professional affairs in
Europe.
1. ESCMID Questionnaire on Professional Affairs
ESCMID and the UEMS Sections of Infectious
Diseases and Medical Microbiology have jointly
developed a questionnaire on professional affairs
24
ESCMID NEWS 02/2008
PROFESSIONAL AFFAIRS
in Clinical Microbiology and Infectious Diseases.
It aims to gather data on how the two specialties
are organized in Europe. Every effort has been
made to make the questionnaire relevant and the
questions “generic”. Specialists in many different
countries have been consulted.
The results of the questionnaire will form the
basis of national websites for Clinical Microbiology and Infectious Diseases under the auspices of
ESCMID. The websites can be regularly updated
and constitute a current record of how CM and ID
are organized throughout Europe, eventually for
all 47 countries. The final data set will also be published in condensed form in ESCMID News.
The preliminary results of the questionnaire will
be presented at the forthcoming Workshop on Professional Affairs in Rome, Italy (see next item).
2. ESCMID Workshop on Professional Affairs
ESCMID is organizing a Workshop on Professional Affairs in Clinical Microbiology and Infectious
Diseases in Rome, Italy. It is entitled Moving Forward in Co-operation.
The objectives of this workshop are to review
the professional status of Clinical Microbiology
and Infectious Diseases across Europe and to discuss new initiatives to improve the organizational
basis for medical practice in these disciplines,
which will have an impact on professional mobility
and recognition. We have recruited an impressive
faculty, and we look forward to lively debate and
discourse. We hope that many of you will take the
opportunity to discuss the future of Clinical Microbiology and Infectious Diseases in Europe.
Clinical Microbiology, in particular, is the tar-
get of structural changes from initiatives outside
and inside the specialty. The external challenges
come from politicians and administrators who believe that laboratory medicine is laboratory medicine irrespective of specialty. The internal challenges are much more positive - they emanate from
the fact that staffing a successful microbiological
laboratory today is vastly different than it was 25
years ago. But the plethora of educations and job
descriptions found today can create internal unrest.
“Working together” is an important issue in years
to come.
Challenges for infectious disease physicians include the lack of recognition of the specialty in
some countries, commissioning of services, and issues of disease-territoriality in which we find ourselves competing with other specialties within
medicine.
The active participation of ESCMID members
in this workshop is of utmost importance, particularly that of young ESCMID members. To those of
you who are today’s decision makers, we ask you
to identify the up-and-coming young CM and ID
specialists who will be tomorrow’s decision
makers and encourage them to come to Rome to
discuss their future. Registration details can be
found on the ESCMID website:
www.escmid.org/PAworkshop.
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ESCMID NEWS 02/2008
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PROFESSIONAL AFFAIRS
25
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Michael Morgan, MD, FRCPath, Consultant Microbiologist
University Hospital of North Durham, UK,
[email protected]
Set between the mountains and the sea, Barcelona is one of the
most beautiful and vibrant cities in Spain and the capital of the
autonomous region of Catalunya. It was an excellent setting for
the largest ECCMID ever, taking place from 19 – 22 April 2008.
This once rather rundown industrial centre has undergone a seismic change that culminated in the hosting of the Olympic Games
in 1992, an event which completely transformed Barcelona. Barcelona has since become something of a Mecca for the world’s
top architects, who have fl ocked there to conjure up an array of
modern structures and avant-garde designs. Many have drawn
their inspiration from the seminal work of Barcelona’s most famous son, the modernist architect Antonio Gaudi, whose unique
style can still be savoured in a number of key buildings around
the city. His masterpiece is the unfinished Sagrada Familia cathedral, but his work can also be seen in his fabulous Guell Park
(declared an artistic monument and world heritage site by
UNESCO) and even in the lampposts and fountains of Plaça
Real. A further attraction is Museo Picasso which houses the
most important and exhaustive collections of Pablo Picasso’s
early work, in particular those between 1895 and 1904. No tour
would be complete without visiting the colourful Gothic Quarter
and savouring the beautiful panoramic view from the top of
Montjuic. La Rambla is the main artery of Barcelona life and
tumbles from Plaça de Catalunya southeast towards the Mediterranean. It is busy around the clock, especially in the evenings
and at weekends. Newsstands, caged bird and fl ower stalls, musicians, tarot-readers and mime artists fill the wide central walkway. The balmy year-round climate (not too steamily hot in summer and with few genuinely cold days in winter) is a further
bonus for the increasing number of visitors.
Readers should refer to the ESCMID website for full details
of the programme, authors and their affiliation, abstracts where
available, etc. Readers should also refer to original publications
by the authors to verify scientific content.
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ÀiÊi“iÀ}ˆ˜}ʈ˜viV̈œ˜ÃÊ`ÀˆÛi˜ÊLÞÊVˆ“>ÌiÊV…>˜}i¶Ê
S. Randolph (Oxford, UK)
Of all emergent infectious diseases, those caused by pathogens
transmitted by arthropod vectors are the most sensitive to climate and most commonly assumed to have been driven by climate change. Tick-borne encephalitis (TBE) is one of the two
most widespread, prevalent and medically significant vectorborne diseases in Europe. Its incidence significantly increased in
Eastern Europe in 1989 and thereafter. A significant discontinuity in temperature conditions in 1989 across Europe could have
created a generally more permissive environment for TBE virus
transmission by improving the circumstances necessary for larval and nymphal stages of the tick to co-feed on rodents. The
pattern of climate change, however, is too uniform within and
between countries to provide the sole, or even the most important explanation for the extreme heterogeneity in TBE epidemiology within Europe. Instead, a multifactorial model in space
and time is more powerful. Analysis of the situation in Central
and Eastern Europe has established that many of these factors
were driven by the socioeconomic changes associated with
the end of Soviet rule, and include climate, land cover, land
use, wildlife, agricultural practices, industrial activities,
(un)employment and income. The same principles may apply to
the periodic epidemics of Crimea-Congo haemorrhagic fever.
i˜ˆ˜}œVœVVˆÊ>˜`ʓi˜ˆ˜}œVœVV>Êˆ˜Û>ÈÛiÊ`ˆÃi>Ãi\ʘiÜʈ˜Ãˆ}…ÌÃÊ
ˆ˜ÌœÊ̅iÊ«>̅œ}i˜ˆVʓiV…>˜ˆÃ“ÃÊ
A. Jonsson (Uppsala, SE)
A transgenic mouse model and bioluminescently labelled meningococci were used to monitor bacterial spread after infection.
Bacteria accumulated in the nasal mucosa, and the colonization
was dependent on meningococcal pili and on GNA992, an outer
membrane protein. Lethal disease was accompanied by bacterial
enrichment in the thyroid gland, and by decreased thyroid hormone T4 levels. Bacterial visualisation demonstrated waves of
bacterial clearance and growth, which selected for bacteria expressing the phase variable outer membrane protein, Opa.
Meningococcal lipooligosaccharide (LOS) has long been identified as a major infl ammatory mediator of fulminant meningococcal sepsis and meningitis. However, both wild-type meningococci and an LOS mutant induced equivalent disease severity
and similar proinfl ammatory responses in TLR4+/+ mice, but
failed to cause fatal sepsis in TLR4-/- mice. Further, fatality associated with meningococcal sepsis in mice is induced by the
proinfl ammatory host response by recognition of one or more
unidentified non-LOS components by TLR4.
œ““Õ˜ˆÌÞÊ “i̅ˆVˆˆ˜‡ÀiÈÃÌ>˜ÌÊ HiVe]nadXdXXjh VjgZjh\Ê …Þ«iÀ‡
ۈÀՏi˜ÌʜÀʍÕÃÌʅޫi¶Ê
F. Tenover (Atlanta, US)
Reports of community-associated methicillin resistant Staphylo-
coccus aureus (CA-MRSA) infections among healthy persons
who have had no recent contact with healthcare and who have
none of the traditional risk factors for MRSA infection are increasing in countries around the world, including the USA, Australia and the Nordic countries. Infections have been observed in
different groups, including children in daycare, sports participants, military recruits, prisoners in institutional settings and
men who have sex with men. The most predominant infection is
skin and soft tissue, although severe and fatal infections have
been reported. Multiple different strain types are causing CAMRSA infections, including ST1, ST8, ST30, ST59 and ST80.
The most predominant community strain in the US is pulse field
gel electrophoresis type USA300 (ST8), which has overtaken
the hospital USA400 strain. The USA300 strain is now not only
circulating within the community, but also within healthcare institutions. Data on the virulence of USA300 strains and the outcomes of CA-MRSA infections are quite divergent. Is CA-MRSA
more a media event than a fearful new epidemic?
ˆvwVՏ̜̇‡ÌÀi>Ìʈ˜viV̈œ˜Ã\ÊÃiÛiÀiÊ`ˆ>LïVÊvœœÌʜÃÌiœ“ÞiˆÌˆÃÊ
B.A. Lipsky (Seattle, US)
Diabetic foot osteomyelitis (DFO) occurs in 20 – 60% of patients
who develop a foot wound, usually via contiguous spread from
soft tissue infection. DFO markedly increases the risk for hospitalization and amputation. Most infections are caused by staphylococci, but other organisms can be involved, sometimes resulting in a polymicrobial infection. Accurate diagnosis of bone
infection is best done by obtaining a bone specimen (either percutaneously or at surgery) for both culture and histology. Among
the available imaging tests, MRI is superior, bone scans being
too non-specific. Clinical signs and symptoms are unreliable, but
the probe-to-bone test is easy and relatively helpful. As for treatment, most authorities recommend resecting any necrotic or
grossly infected bone. Recently, retrospective case series have
shown that some cases of presumed osteomyelitis can be put into
long-term remission with antibiotic therapy alone, usually with
highly bioavailable antibiotics given for a prolonged period (3
months or longer). If one removes all infected and necrotic bone,
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the duration of treatment can be considerably shorter (days to
weeks). Some evidence suggests that including rifampin (combined with at least one other anti-staphylococcal antibiotic) improves outcome; clindamycin and beta-lactam agents are also
frequently used. No adjunctive treatment (e.g., hyperbaric oxygen, granulocyte colony stimulating factor, larval biotherapy)
has been proven beneficial. When treatment of osteomyelitis
fails, surgeons should opt for the most minor amputation compatible with good residual foot function.
ÃÜVˆ>̈œ˜Ê LiÌÜii˜Ê }ÀœÕ«Ê Ê LiÌ>‡…>i“œÞ̈VÊ ÃÌÀi«ÌœVœVVˆÊ >˜`Ê
ÛՏۜÛ>}ˆ˜ˆÌˆÃʈ˜Ê>`ՏÌÊܜ“i˜\Ê>ÊV>ÃiÊVœ˜ÌÀœÊÃÌÕ`ÞÊ
M.J. Bruins, R.A.M.J. Damoiseaux, G.J.H.M. Ruijs
(Zwolle, Hattem, NL)
Group A streptococci are established as a cause of vulvovaginitis
in children, but evidence of infection in adult women is limited.
The significance of group C, F and G streptococci in vaginal
fl ora is also unclear. This case control study investigates the association between non-group B beta-haemolytic streptococci
and vulvovaginitis in adult women. Non-group B streptococci
were isolated from 86 (8.5% of 1’010) cases and from 6 (2.9%
of 206) controls (P<0.01). The significant difference was caused
by group A streptococci that were isolated from 49 (4.9%) cases
and not from any of the controls (P<0.01). Isolation rates of
group C, F and G streptococci from cases were low and did not
differ statistically from those from controls. Group A betahaemolytic streptococci are associated with persistent vaginal
discharge in women aged between 30 and 60 and should be diagnosed and reported as a pathogen in vulvovaginitis. The role of
other non-group B streptococci requires more study because of
the low numbers isolated. For adequate management of vaginal
discharge, culturing is necessary if initial treatment fails.
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"«Ìˆ“ˆâˆ˜}ʜÕÌVœ“iÃ\Ê}iÌ̈˜}ʈÌÊÀˆ}…ÌÊvÀœ“Ê̅iÊÃÌ>ÀÌÊ
Y. Carmeli (Tel Aviv, IL)
Resistance to antimicrobial drugs is a growing health and economic concern. Rates of resistance to community- and hospitalacquired Gram-negative and Gram-positive pathogens have risen
significantly over the past several years. Infections caused by
these drug-resistant pathogens are associated with greater morbidity and mortality, prolonged hospitalizations, and increased
costs, compared with infections from sensitive strains. The early
identification of patients at higher risk for polymicrobial-resistant infections is a key factor in guiding the selection of empiric
antibiotic therapy. Selection of agent(s) from various classes of
antibiotics should be individualized based on the patient’s clinical status and renal function and by the agent’s microbiological
activity (coverage), resistance characteristics, and therapeutic
dynamics. The prompt selection of appropriate broad-spectrum
empiric antibiotic therapy is essential to provide adequate cover-
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European MIC breakpoints for antimicrobial susceptibility testing
are now harmonized by EUCAST: why European harmonization?
D. Brown (Cambridge, UK)
At least seven different MIC breakpoint committee guidelines
for antimicrobial susceptibility testing have been used in Europe.
Consequently Europe has had several different sets of antimicrobial breakpoints and a range of variations in technical methods.
It became increasingly evident that harmonization of breakpoints
was necessary both for therapy and resistance surveillance.
ESCMID set up EUCAST in 1997 with a representative from
each European country and six representatives from industry. In
2002 EUCAST was restructured and the major responsibility for
the work of EUCAST was taken on by the active national breakpoint committees in Europe. A Steering Committee was formed,
proposals from which are distributed to the EUCAST General
Committee, relevant expert groups and industry for consultation.
The final decision is made by consensus in the Steering Committee, taking account of any comments made during consultations.
In this process the expertise of the national breakpoint committees is utilized, there is wide consultation on proposals and the
national committees take responsibility for implementation of
decisions. Subcommittees have been set up to deal with specific
topics including susceptibility testing of fungi and anaerobes,
and expert rules in susceptibility testing. A website has been established (www.eucast.org) that gives details of EUCAST activities, EUCAST breakpoints and publications. Another website
has been developed for the collection of MIC data and its presentation as species-specific wild type MIC distributions.
EUCAST has been funded by ESCMID, the national breakpoint
committees, a grant from the EU and now by ECDC. Industry
does not contribute financially but is asked to contribute data
required for determining breakpoints and to comment on proposed breakpoints. EUCAST has achieved harmonization of
most existing breakpoints in Europe. It has a formal relationship
with EMEA regarding the setting of breakpoints for new agents
and the revision of breakpoints for existing agents. The process
has been applied to several new drugs. Documents on various
aspects of susceptibility testing have also been published.
Usage of carbapenems significantly increases the rate of new
colonization due to antibiotic-resistant bacteria in hospitalized
patients
E. Tacconelli, G. De Angelis, M. Cataldo, et al.
(Rome, Siena, Brescia, Florence, Milan, IT)
28
ESCMID NEWS 02/2008
SCIENCE AND EDUCATION
During a 12-month prospective multicentre cohort study, new
acquisitions of antibiotic resistant bacteria per 1’000 days of
treatment with antibiotics were investigated. The aims were to
establish the mean time to acquisition and to measure the patients’ risk factors for acquiring antibiotic-resistant bacteria. Nasal and rectal samples were taken from patients before starting
antibiotics and then on days 2, 4, 7, 15 and 30. The resistant bacteria that were investigated included methicillin resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci
(VRE), and ciprofloxacin-resistant Pseudomonas aeruginosa
(CR-PA). A total of 6’245 swabs from 864 patients were processed, with 5% of patients acquiring an antibiotic-resistant organism. The incidence of antibiotic-resistant bacteria per 1’000
days of therapy varied among antibiotics, with the highest being
carbapenems with 14/1000 patient days and, in a multivariate
analysis, carbapenems, along with length of hospital stay and
age, were significant predictors for acquisition of antibiotic-resistant bacteria.
Comparison of antibiotics with placebo for the treatment of
presumed acute bacterial sinusitis: a meta-analysis of
randomized controlled trials
M. Falagas, K. Giannopoulou, K. Vardakas, et al. (Athens, GR)
There is controversy regarding the benefit of antibiotics for the
treatment of patients with presumed acute bacterial sinusitis. In
a meta-analysis of randomized, placebo-controlled trials (RCTs),
the effectiveness and safety of antibiotics for this indication was
evaluated. Sixteen RCTs were included, (three of which performed exclusively in children), involving 21 antibiotic arms (8
amoxicillin, 4 penicillin V, 3 amoxicillin/clavulanate, and 6 other antibiotics). The study concluded that antibiotic treatment of
presumed acute bacterial sinusitis compared to placebo is associated with a rounded 10% added benefit in clinical outcomes, at
a cost of an approximately equal increase in the rate of adverse
events. Considering that observed adverse events are generally
not serious, and that not using antibiotics may carry an appreciable risk of disease complications, we believe that clinical benefits obtained from antibiotic use, justify the risks associated
with such treatment.
European Surveillance of Antimicrobial Consumption (ESAC):
outpatient parenteral antibiotic treatment in Europe
S. Coenen, A. Muller, and the ESAC Project Group
Outpatient parenteral antibiotic treatment represents more than
1% of the total outpatient antibiotic use in only six out of the 20
European countries studied. As for the total outpatient antibiotic
use and the use of different antibiotic groups and substances, this
striking variation in the proportions of parenteral antibiotic use
in Europe (see figure) needs more data for explanation.
Proportion of parenteral on total outpatient antibiotic use in DDD
per 1’000 inhabitants per day in 20 European countries in 2005
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age for the pathogens of concern and “Getting it Right from the
Start”. The use of pharmacokinetic (PK) and pharmacodynamic
(PD) simulations can help guide the decision-making process for
the selection of antibiotic(s), dosage(s), and duration of
infusion(s). For example, extending infusion times may lead to
better outcomes for the treatment of infections caused by organisms with high minimum inhibitory concentration (MIC) values
by extending the time above the MIC without requiring an increase in dosage.
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Respiratory tract infections
Healthcare-associated bacteraemic pneumonia: aetiology,
severity of disease and outcomes
M. Salvado, L. Lozano, E. Calbo, et al. (Terrassa, ES)
Recent studies have been focused on healthcare-associated pneumonia (HCAP) trying to distinguish them from truly community-acquired (CAP) or hospital-acquired pneumonia (HAP). This
study, conducted in a 450-bed acute care teaching hospital aims
to describe the aetiology and outcomes of a cohort of patients
with bacteraemic pneumonia (BP), dependent on their relation to
the healthcare system. 175 episodes of BP were identified and
the results outlined below.
In conclusion, the majority of BPs are seen in patients with
CAP. Severity of disease and relation with the healthcare-system
are important predictive factors of increased mortality. Although
the aetiology in HCAP is similar to CAP, its mortality parallels
that of HAP, showing the great impact of host factors on outcome.
Acute exacerbations of chronic obstructive pulmonary disease
A. Torres (Barcelona, ES)
Most mild exacerbations of chronic obstructive pulmonary disease (COPD) would not require antibiotic treatment because
they are viral in origin or because they are not infectious. However, in clinical practice it is difficult to distinguish between
these two situations. A recent study by this group confirmed that
the existence of sputum purulence is a sensitive and specific variable associated with positive bacterial cultures in bronchoscopic
samples. However, there are patients who cannot expectorate
and some of them may have a bacterial infection. In these cases,
biological markers could help to differentiate between viral and
bacterial infections. In one randomized trial, procalcitonin (PCT)
has been found to be useful in the decision to continue or discontinue antibiotics without recurrence problems. The limitations
are the need of a blood sample and the availability of methods
able to detect small amounts of PCT. In terms of pathogens, one
of the most controversial issues is the role of Pseudomonas aeruginosa, with some studies reporting isolation in 10 to 15% of
exacerbations. Antipseudomonal treatment is recommended
HAP
CAP
HCAP
25 patients
(14.2%)
115
(65.3%)
36
(20.5%)
62.5
(SD 17.3)
57.8
(SD 20)
75.6 y
(SD 12.48)
Men
56%
69.6%
55.6%
0.2
Co-morbidity by
Charlson score
2.57
1.55
2.03
0.05
Streptococcus
pneumoniae isolated
36%
93%
71.4%
0.001
Staphylococcus aureus
isolated
12%
1.7%
2.8%
0.037
Pseudomonas aeruginosa
isolated
24%
0.9%
11%
0.001
No. of patients
Mean age
p-Value
0.001
Pitt score
2.8
1.03
1.14
0.01
Shock
20%
10.4%
11%
0.4
In-hospital mortality rate
40%
10%
43%
0.001
Severity of disease (OR)
1.2
3.9
5.6
0.007, 0.02 &
0.001 respect
ESCMID NEWS 02/2008
SCIENCE AND EDUCATION
29
when two out of these four variables (in the ERS guidelines) are
present: FEV1<30%; prior antibiotic treatment; long-term treatment with steroids; and prior colonization with or isolation of P.
aeruginosa.
Enterococcal infections
New insights into the pathogenesis and treatment of
enterococcal endocarditis
B.E. Murray (Houston, US)
Recent studies have suggested that shorter aminoglycoside (AG)
regimens and, for enterococcal strains with high-level resistance
to all AG, the combination of ampicillin with ceftriaxone may
also have adequate efficacy for E. faecalis infective endocarditis
(IE). Therapy for endocarditis caused by vancomycin-resistant
E. faecium remains more problematic. Relatively little is known
about the pathogenesis of enterococcal IE. Recent studies by this
group have identified pili in E. faecalis, encoded by the ubiquitous ebp (for endocarditis and biofilm related pili) locus and
made up of three subunits, each of which have the characteristics
of cell wall anchored MSCRAMMs. These pili are important in
initiating biofilm formation, in experimental IE (EIE) and in serum-induced adherence to fibrinogen, suggesting involvement in
initiating E. faecalis IE. The ebp locus is regulated in part by the
fsr system, a homologue of the agr system of staphylococci. The
group also identified a ubiquitous collagen adhesin, Ace (also an
MSCRAMM), whose expression is induced by serum and collagen, and found that this adhesin is also important in E. faecalis
EIE. Similarly, its homologue (Acm, an adhesin to collagen of E.
faecium), is important in the pathogenesis of E. faecium EIE and
in adherence to heart valves. Preliminary data suggest that immunization against recombinant Ace or Acm is protective against
EIE by the producing species. Another factor shown to be importance in E. faecalis IE is gelatinase, a protease produced by
only ~60% of E. faecalis despite the fact that the encoding gene
gelE is found in over 90% of stains; deletion of part of the regulatory locus, fsr, explains the lack of gelatinase production by
many strains. Aggregation substance, encoded by pheromone responsive plasmids found in some E. faecalis, and a cytolysin/
hemolysin may influence the size of EIE vegetations and mortality produced by E. faecalis, respectively. Additional studies are
needed to define the role of other factors in enterococcal EIE and
the ability of passive or active immunization to prevent this disease.
First description of Enterococcus faecalis small colony variant
in a patient with aortic valve endocarditis
N. Wellinghausen, A. Sigge (Ulm, DE)
Small colony variants (SCV) constitute a slow-growing subpopulation of bacteria with distinctive phenotypic and pathogenic
traits. A 74-year old female patient who underwent aortic valve
replacement with a bovine bioprothesis three years ago present-
30
ESCMID NEWS 02/2008
SCIENCE AND EDUCATION
ed to the emergency department with persistent fatigue. By
transoesophageal echocardiography, vegetations on the aortic
valve were documented. In two out of two blood cultures E. faecalis susceptible to ampicillin and imipenem, and intermediate
susceptible to rifampicin was grown. In addition to typical E.
faecalis colonies, a SCV phenotype consisting of small pin-point
colonies was detected in both blood cultures. Typing by pulsedfield gel electrophoresis revealed clonal identity of both phenotypes and antimicrobial susceptibility patterns were comparable.
The patient was treated with imipenem and rifampicin for six
weeks and suffered from a relapse of the endocarditis three
weeks later, requiring replacement of the prosthetic aortic valve.
After another 6 weeks of antimicrobial therapy with ampicillin
and gentamicin the patient recovered. Thus, Enterococcus faecalis is able to form a SCV phenotype with impaired growth characteristics and distinctive ultrastructural alterations observed by
light microscopy and EM. Further studies are underway to investigate alterations in cellular metabolism in enterococcal
SCV.
Clostridium difficile associated disease
Clostridium difficile: new and old treatment options
E. Bouza (Madrid, ES)
Metronizadole and vancomycin are currently the drugs of choice
in the treatment of C. difficile (CD) infection, but both have limitations and adverse effects. Metronidazole (MET) has been
linked to non-responses and, although low at present, resistance
is known to exist, whilst the increased use of vancomycin may
lead to an increase in vancomycin resistance in other organisms.
New antimicrobial agents active in vitro against CD include: teicoplanin, ramoplanin, daptomycin, telavancin, linezolid, nitazoxanide, tiacumicins B and C, and rifaximin. Nitazoxanide is
an antihelminthic and antiprotozoal agent that has shown equivalence in studies compared to MET. Rifaximin, a non-absorbable
derivative of rifampicin and approved for traveller’s diarrhoea,
has been shown to be as effective as vancomycin in a hamster
model, whilst tiacumicins have been shown to be active against
ribotype 027. Intravenous immunoglobulins have been used to
treat patients with severe disease, but they are expensive and
there are no good studies to support their use. There is conflicting evidence on the use of probiotics, with one study showing no
efficacy and the other showing an advantage over a control
group. A hyperimmune bovine gammaglobulin that neutralizes
the effects of CD toxins is under development. Surgery is a last
resource for the treatment of unmanageable CDAD with toxic
megacolon or colon perforations.
Recurrent Clostridium difficile-associated disease: an
emerging problem requiring novel treatment strategies
J. Keller (Amsterdam, NL)
Recurrent CD is an increasing problem with limited treatment
options. Initial treatment with MET or vancomycin during 10 –
14 days is effective in only 70 – 85% of patients. Further treatment of relapse consists of a second course of antibiotics, followed by a tapered-pulsed vancomycin regimen lasting for
several weeks. The failure of treatment may be explained by the
failure of the antibiotics to eradicate CD spores which will then
be able to grow out in a bowel that lacks the normal colonic flora. The use of enemas containing donor stool was trialled in the
1950s and has been used in a limited number of patients subsequently, with clinical improvement seen in the majority of patients. The efficacy of the faecal therapy may be explained by the
restoration of faecal physiology. Previously, there have been no
randomized controlled trials, but there is currently one underway
in the Netherlands. All donor patients are screened for infection
and ensured that they have a normal defecation pattern. A fresh
faeces sample is obtained from them less than 6 hours before
infusion and suspended in NaCl. The donor faeces is then infused in jejunum or in coecum after the patient has received 4
days of vancomycin and a bowel lavage with kleanprep. To date,
eleven patients have been treated and no side-effects or recurrences of infection have been observed.
Emergence of reduced susceptibility to metronidazole in
Clostridium difficile
S. Baines, R. O’Connor, W. Fawley, et al. (Leeds, UK; Rome, IT;
Leiden, NL)
Resistance to MET or vancomycin in CD has rarely been reported and generally limited to occasional strains. This group
now repeats previous surveillance for MET and vancomycin resistance in common CD ribotypes. No reduced susceptibility to
vancomycin was observed. All CD ribotype 106 or 027 isolates
were fully susceptible to MET (MICs <2 mg/L). However, 21
(24%) CD ribotype 001 isolates had reduced susceptibility to
MET by spiral gradient endpoint (SGE). The geometric mean
MIC was 3.5 mg/L (P<0.001). Results varied according to the
method used, and both the agar base and broth used to prepare
inocula affected the MET MIC values for CD. Neither E-test nor
CLSI methods detected the CD strains with reduced susceptibility to MET, but this was confirmed by the alternative AI method.
The geometric mean MICs of CD ribotype 001 isolates from
1995–2001 (n = 72) and those identified by SGE with reduced
susceptibility to MET (n = 21) were 1.03 and 5.9 mg/L, respectively (P<0.001). MLVA typing revealed subgroups of ribotype
001 isolates that were more closely associated with reduced susceptibility to MET than others. This study confirms the emergence of reduced susceptibility to MET, which is easily missed
unless appropriate methods are used. Increased vigilance is
needed to identify reduced antibiotic susceptibility in CD, and to
detect increased treatment failure associated with MET.
Infection control
Is it time for pan-European surveillance of healthcare-related
infections?
P. Gastmeier (Berlin, DE)
International comparisons yield interesting insights regarding
quality of care, beyond the field of healthcare-associated infection (HAI) prevention. Therefore, the exchange of experiences
among national surveillance systems should be encouraged.
However, the interpretation of differences of HAI rates should
be made very carefully. Differences in healthcare systems, legal
and cultural aspects, as well as differences in the methods of the
surveillance systems, may have an enormous influence. A further most crucial aspect of surveillance data is their validity, and
its evaluation is very difficult. The European Centre for Disease
Prevention and Control has to decide in the future which level of
European surveillance of HAI should be achieved. Of course
there are several options: 1) The harmonization process of the
individual national surveillance networks should be continued to
finally achieve a uniform European HAI surveillance system.
This process already started with Hospitals in Europe link for
infection control through surveillance (HELICS; since 1994)
and was continued with Improving patient safety in Europe
(IPSE) activities (since 2005) for surveillance of surgical site infections and HAI surveillance in Intensive care units. 2) The harmonization process should be stopped because it is not really
feasible to create a useful European database, and the efforts
should be concentrated on a regular exchange of experience between the national networks, on the organization of validation
studies, joint risk factor studies, etc. 3) ECDC should create a
pan-European surveillance for infections with problems in identification and application of the definitions, e.g. nosocomial
CDAD/1000 patient days or nosocomial laboratory confirmed
BSI per 1000 patient days (adjusted according to the frequency
of diagnostics). 4) ECDC should start pan-European surveillance
with a totally new European surveillance system with interesting
or “at risk” patient groups, without the need for modification of
the existing systems (e.g. bone marrow transplant recipients,
very low birth weight newborns, etc.). The advantages and disadvantages of the different strategies were discussed.
Copy and paste – is the search and destroy policy suitable for
Europe?
C.M.J.E. Vandenbroucke-Grauls (Amsterdam, NL)
Since the early 1980s the Netherlands has adopted a search and
destroy policy with respect to methicillin-resistant Staphylococcus aureus (MRSA). This policy implies a national guideline for
control, with search for carriers among defined groups of patients and healthcare workers, strict isolation and treatment of
carriers. The guideline is enforced by the Health Inspectorate. In
addition, a national surveillance system has been implemented.
From this surveillance we know that, as of 2006, MRSA was
detected in approximately 2’000 persons (both patients and
ESCMID NEWS 02/2008
SCIENCE AND EDUCATION
31
healthcare workers; the number comprises carriers and infected
persons). This very low number is confirmed by the EARSS
data: The Netherlands is one of the countries in Europe with the
lowest burden of MRSA. The stringent Dutch policy has been
applicable for so many years, because the number of carriers is
so low. We realize that screening and strict isolation “the Dutch
way” are impossible when the number of MRSA carriers becomes too high. From the Dutch experience, however, lessons
can be learned and that may provide a basis for “copy and paste”
of part of the Dutch approach in countries with a higher burden
of MRSA. Among these are the national approach and the national surveillance, which provide support to all healthcare
workers involved and motivation to keep up the efforts.
Laboratory and typing methods
MLST – 10 years of experience
M. Maiden (Oxford, UK)
Since multi locus sequence typing (MLST) was proposed in
1998 as a portable approach to the identification of bacterial
clones, it has become a gold standard method for the characterization of many bacterial pathogens and a number of non-pathogens. MLST has made it possible to compare the bacterial iso-
lates obtained in different parts of the world and at different
times simply and accurately using generic techniques. In addition to solving many of the problems inherent in the characterization of isolates from diverse recombinogenic bacteria, MLST
has also provided data that have enabled extensive studies of
bacterial population genetics, speciation, and evolution, providing substantial added value to epidemiological studies. The
MLST approach also provides indications as to the most efficient means of exploiting the next generation of DNA sequencing machines.
Use of DNA microarrays in molecular typing
J. Lindsay (London, UK)
Microarrays are solid supports spotted with thousands of tiny
DNA probes that can be used to determine rapidly which genes
are present in a bacterium or sample. They have caused a revolution in our understanding of bacterial population structures and
how they vary and evolve, and have also helped to identify markers of virulence or epidemiology. Microarrays are also extremely
valuable for developing and validating improved routine typing
methods. In the typing laboratory where methods need to be
cheap, rapid, accurate and reproduceable, microarrays technology is expensive and experimental. However, this is changing and
when printed with appropriate probes and validated, their uses
are only limited by the ability to interpret the data generated.
Latin American Workshop on Mechanisms of
Resistance to Antimicrobial Agents
Juan Carlos Tinoco, Workshop Organizer,
[email protected]
Jordi Vila, ESCMID Scientific Affairs Officer, [email protected]
With the support of the European Society for Clinical Microbiology (ESCMID), in collaboration with the American Society for
Microbiology (ASM) and the Mexican Association for Infectious Diseases and Clinical Microbiology (AMIMC), a Latin
American Workshop on Mechanisms of Resistance to Antimicrobial Agents was held from 9 – 10 June 2008 in Mexico City.
The objective of the workshop was to provide the participants
with current background information and offer a practical session on the study of antimicrobial resistance mechanisms and
the molecular epidemiology in clinical relevant Gram-positive
and Gram-negative microorganisms.
The event took place at the Instituto Nacional de Ciencias
Medicas y Nutricion Salvador Zubirán (INCMNSZ) in Mexico
City. 159 students from five countries including Venezuela, Honduras, Canada, Singapore, and Mexico met for a more theoretical presentation during the morning and 30 students from se-
32
ESCMID NEWS 02/2008
SCIENCE AND EDUCATION
lected institutions from these countries participated in the
afternoon microbiology practice session.
The first day was dedicated to Gram-positive bacteria. In the
first presentation, Jose Sifuentes-Osornio, from the INCMNSZ,
Mexico City, offered a review of the regional epidemiology of
antimicrobial resistance in these organisms. Stephen Brecher,
from VA Boston Healthcare System, USA, discussed the evolution, mechanisms, and laboratory detection of antibiotic resistance in S. aureus and coagulase-negative Staphylococcus. The
dissemination to the community of methicillin-resistant S. aureus was emphasized. Later, David Farrel, from GR Micro Limited in the UK, lectured on the epidemiology of antimicrobial
resistance in S. pneumoniae, with a special analysis of macrolide-resistance and the impact of vaccination on this problem.
Stephen Jenkins, from Weill Cornell Medical College in New
York, presented relevant aspects of macrolide-resistance in
group A streptococci and Stephen Brecher, covered the important aspects of the evolution of bacterial resistance in enterococci and how to detect it in the laboratory. As the final talk of
the day, Stephen Jenkins gave a lecture titled Resistance among
less common Gram-positive bacteria and PK/PD presentation.
Key individuals for the
Workshop: Juan Carlos Tinoco,
Rita Delia Díaz, Patrice
Nordmann, Giuseppe Cornaglia,
Jordi Vila, Gian Maria Rossolini,
José Sifuentes-Osornio,
Guillermo Ruiz-Palacios
Using two clinical cases as an example, he emphasized the problems in the isolation, identification and interpretation of the susceptibility tests in some of the Gram-positive bacillus not commonly found in clinical practice. He finished his presentation by
stressing the importance of the application of the pharmacokinetic and pharmacodynamic principles in the antibiotic prescribing.
On the following day, Gram-negative bacteria were reviewed.
Celia Alpuche, from the Instituto de Diagnostico y Referencia
Epidemiologica in Mexico City, reviewed the most important aspects of the regional epidemiology of bacterial resistance in
Gram-negative bacilli. Acinetobacter baumannii, as the paradigm of multiresistant bacteria, was then presented by Jordi Vila,
from the Hospital Clinic and School of Medicine, University of
Barcelona, Spain. The multiple mechanisms for antimicrobial
resistance, its molecular basis and its evolution together with
clinical impact were analyzed in this lecture. Giuseppe Cornaglia from Verona University, Italy, discussed the epidemiology
and mechanisms of antimicrobial resistance in Pseudomonas.
Gian Maria Rossolini, from Siena University, Italy, lectured on
the emergence, dissemination and clinical impact of the carbapenemases in Enterobacteriaceae and non-fermentative Gramnegative bacilli. The methodology for its detection in the microbiology laboratory was also discussed. Patrice Nordmann, from
Hospital Bicetre, Paris, presented information related to extended spectrum beta-lactamases, with special emphasis on their epi-
demiology and laboratory methodology to detect them. In the
last presentation, Jordi Vila discussed the mechanisms and epidemiology of quinolone resistance in Enterobacteriaceae.
The programme was designed to allow enough time for a
Q&A session after each presentation and the students participated eagerly and openly. Additionally, the instructors and students
continuously interacted even during the coffee breaks.
During the afternoon, practical sessions allowed participants
to learn about some applied tools to search for mechanisms of
resistance to antimicrobial agents and reveal molecular epidemiology. Part of or the complete procedure of plasmid analysis,
extraction and separation of outer membrane proteins by one dimensional gel electrophoresis, REP-PCR and pulsed field gel
electrophoresis were performed. Each session started with a
short description about the background of the tool and after that
the students formed six groups of five students to implement the
procedure.
At the end of the meeting, Giuseppe Cornaglia, current president of ESCMID, extended an invitation for students to take an
interest in the ESCMID programmes. He also suggested organizing student exchange and investigational programs.
ESCMID NEWS 02/2008
SCIENCE AND EDUCATION
33
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Hartmut Lode, Head of Research Center for
Medical Studies, Berlin, Germany,
[email protected]
This very successful course on Infections with
Multiresistant Pathogens was held in Berlin, Germany, on 14 and 15 March 2008, at the Institute for
Clinical Pharmacology and Toxicology of the
Charité University Campus Benjamin Franklin. W.
Graninger (Vienna), H. Lode and R. Stahlmann
(Berlin) organized the event under the auspices of
the Paul-Ehrlich Society for Chemotherapy, the
Robert-Koch-Institute and the German Society for
Infectious Diseases. It addressed an urgent clinical
and therapeutic problem physicians are faced with
in their daily struggle against infections caused by
multiresistant Gram-positive and Gram-negative
pathogens. Patients in ICUs and haematological
and transplantation departments are especially at
risk for these infections and exhibit high mortalities. Optimizing prevention, diagnostic measurements and appropriate therapeutic decisions based
on pathogenic insights is a great challenge for physicians responsible for these patients. Altogether,
40 participants from 17 European countries and
four non-European countries, specialists and fellows in infectious diseases, infection control,
microbiology, intensive care medicine, oncology,
chest diseases and transplant medicine gathered in
Berlin for this two-day meeting. Seventeen highquality lectures were held by well-known specialists in these areas who presented the latest knowledge on epidemiology, diagnostics/microbiology,
therapy, infection control and prevention, illustrated by many cases from the lecturers’ own clinical
experience.
The course focused on nosocomial infection
with special topics in haematological and ventilated patients, addressed the pharmacokinetic/pharmcodynamic aspects of antimicrobial therapy and
covered current standard therapies. A greater portion of the course was reserved for new developments in antimicrobiological drug research with
emerging new compounds that recently have entered the market or are pending approval in the
near future. These include new cephalosporines,
tetracyclines and glycopeptides.
One of the biggest problems clinicians currently
face is the increasing resistance against antibiotics
which includes the selection of multi-drug resistant strains exacerbated by wide-spread and imprudent use of antimicrobial agents. The consequences
can be severe: As a result of vancomycin overuse,
the management of infections in vancomycin-re-
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new compounds such as daptomycin, linezolid,
tigecycline and quinupristin/dalfopristin, while
beta-lactams and glycopeptides are useless (W.
Graninger, Vienna).
Also multiresistant strains of Streptococcus
pneumoniae and Staphylococcus aureus challenge
professionals all over the world every day. Antibacterial resistance in S. pneumoniae is increasing
worldwide, affecting beta-lactams, macrolides and
fl uoroquinolones, depending on the geographical
region. In Germany, antibiotic resistance rates to
penicillin and macrolides have increased considerably from approximately 8.5% in 1997 to 28% in
2006. Rates are even considerably higher in some
other European countries. Particularly, macrolide
resistance has become a global problem and relates
to clinical failure. Macrolide monotherapy should
thus no longer be used as a first line therapy against
S. pneumoniae. Of more concern, 40% of pneumococci display multi-drug resistant phenotypes, with
a highly variable prevalence among countries.
Multiple antibiotic resistance (resistance to ≥ 3
classes of antibiotics) first emerged in South Africa
in 1978. Pneumococci showed a clonal spread of
resistant mutants worldwide since then (M. van der
Linden, Aachen).
Vaccination remains an interesting alternative
to reduce the risk of developing S. pneumoniae infection. However, the limitation of this approach
lies in the difficulty of including the most prevalent serotypes, which can result in selection of
non-vaccinal multi-drug resistant clones. Currently, a multi-resistant 19A strain is emerging worldwide (M. Pletz, Hanover).
Another germ that causes problems is methicillin-resistant S. aureus (MRSA) which colonizes
the nasal vestibule in about 30% of healthy humans
and becomes pathogenic in predisposed patients
after endogenous or exogenous transmission routes
by contact infection. MRSA often are multiply resistant; in case of severe infections, treatment options are limited with the consequence of enhanced
lethality. Spread of nosocomial MRSA is mainly
associated with clonal dissemination. New clonal
lineages evolve and displace the older ones. The
reasons for “epidemicity” are still unknown. Community MRSA are an example of recent evolution
of MRSA with particular capacities for causing
necrotizing infections and for successful competition with the resident colonizing methicillin-sensitive S. aureus population outside the hospital setting (W. Witte, Wernigerode).
G. Cornaglia (Verona, Italy) reported that the
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U.S. Food and Drug Administration (FDA) recently approved the first rapid blood test for MRSA. As
a strategy to control and prevent MRSA infection
and to avoid spread of MRSA in healthcare facilities, patient isolation and strict compliance with
hand hygiene is recommended. Screening of former
MRSA carriers, contact patients and patients at
risk supported by an alert system can prevent infections with MRSA, but is often restricted by the
anticipated costs of implementation, despite the
fact that the economic benefit from prevented infections substantially outweighs the cost (P. Gastmeier, Berlin).
H. Lode (Berlin) emphasized that antibiotic resistance increases mortality and health care costs
of nosocomial infections. Therefore, combatting
increasing antibiotic resistance requires a new approach. Traditionally antibiotic therapy has been
driven by concerns about the development of resistance and costs as well as the desire to avoid the
use of antibiotics when infections are not confirmed. As a consequence, therapy was often initiated with narrow-spectrum antibiotics. The provision of optimal antibiotic therapy in severely
affected patients should not cause a delay in effective therapy. It must also be characterized by broad
coverage of relevant pathogens and activity against
resistant organisms and be highly active at the site
of infection.
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In multiple drug therapy, each clinician should
be aware of interactions between the applied drugs,
a topic that is often neglected in everyday life on a
hospital ward. The consequences of interactions
are manifold and may result in reduced efficacy
(drug failure) and enhanced effects and risks for
toxicity that call for dosage adjustment as R. Stahlmann (Berlin) pointed out in his lecture.
In discussions about pathogens with increasing
clinical relevance, fungi must not be forgotten and
this allowed for two exciting talks about the clinical and therapeutic aspects of resistance in fungal
infections by G. Maschmeyer (Potsdam) and S.
Schwarz (Berlin).
This two-day postgraduate education course
was a raving success for its organizers. The cornerstone of its success was the excellence of the invited speakers, the soundness of the material presented and the stimulating atmosphere which
nurtured lively discussions between audience and
lecturers. The meeting was a good opportunity for
the participants to enhance their network contacts
and to initiate and establish future interchange between the different researchers or research groups.
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Marco R. Oggioni, LAMMB, Dip. Mol. Biol.
University of Siena, organizer of the 47th
ESCMID Postgraduate Technical Workshop,
Secretary of EMESG, [email protected]
The 47th ESCMID Postgraduate Technical Workshop, Gene expression during infection, was held
at the Certosa di Pontignano (Siena, Italy) from 2
to 5 March 2008. Marco Oggioni of the University
of Siena and Matthias Wittwer of the University of
Bern organized the workshop under the auspices of
both the University of Siena and EMESG, the
ESCMID Meningitis Study Group. The main venue of the workshop was the marvellous medieval
monastery, the Certosa di Pontignano, near Siena,
which is the Congress Centre of the University of
Siena. All participants and faculty were hosted at
the Certosa and all lectures took place there. The
yards and gardens of the monastery were an excellent setting for informal discussion and interaction
during coffee breaks and free time for the whole
workshop duration. The workshop was focused on
the theoretical and practical approaches involved
in studying the host-pathogen interaction, especially with meningitis and meningeal pathogens.
The objective of EMESG is to promote and disseminate studies and knowledge on meningitis. As
stated in the statutes of EMESG, a multidisciplinary approach is necessary for the study of bacterial meningitis necessitating the inclusion of scientists active in the field of clinical and molecular
microbiology, neurology and infectious diseases. It
is, therefore, the objective not only of EMESG, but
also of this first EMESG joint workshop, to facilitate cooperation between diverse disciplines focusing on meningitis. The workshop was aimed at
providing updated theoretical and practical information on methods for gene-expression analysis
during infection. It was organized in two lecture
sessions with seminars held by the workshop faculty, four sessions with short talks given by the
workshop participants and two practical workshops
offered to the participants divided into smaller
workgroups.
The theoretical lectures provided examples of
how gene-expression data can be used to study
host-bacteria interactions. The opening lecture on
pathophysiological aspects of bacterial meningitis
and the use of microarray technology was held by
Matthias Wittwer of the University of Bern, who
gave a general overview on bacterial meningitis
from the point of view of an infectious disease specialist. His presentation firstly encompassed the
epidemiology and clinical aspects of the disease as
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well as the underlying cellular mechanisms and
secondly showed the use of the microarray technology as a valuable tool to decipher the transcriptomic alterations underlying the complex pathophysiological processes of bacterial meningitis.
The next lecture by Marco Oggioni of the University of Siena described the use of real-time PCR in
detecting gene-expression patterns in bacteria infecting mice. The main conclusion of this presentation was that patterns of gene expression are an
important tool to suggest the physiology of bacteria during infection, and that a great amount of experimental work is needed downstream of geneexpression analysis to confirm the relevance of the
experimental data. It takes at least two years of experimental work for a student/postdoc to confirm
the significance of the up- or down-regulation of a
single gene during infection; this underlines the
importance of experimental work to confirm in
silico results, which often is perceived to be a
stand-alone conclusive experiment. The medical
aspects of fungal meningitis were discussed by
Stefan Zimmerli of the University of Bern. He described the clinical picture of Aspergillus infection
and introduced an animal model of mould meningitis. His presentation demonstrated how experimental Aspergillus meningoencephalitis that closely mimics key features of human cerebral
aspergillosis can be used to study the pathophysiology of this disease. Gene-regulation patterns
identified by microarray analysis provide both important insights into the host’s response to infection and guidance for confirmatory experiments on
the protein level.
On the third day of the workshop, two lectures
focused on host response to infection, one on the
microbiology of Neisseria infection and two on antimicrobial resistance. Aras Kadioglu gave a lecture on host immune responses to pneumococcal
infection focusing on models of nasopharyngeal
carriage and acute pneumonia. His lecture highlighted the role of neutrophils, surfactant proteinD and CD4 T-cells in early host protection, and the
counteracting roles of pneumococcal virulence
factors such as pneumolysin and neuraminidases.
He gave examples of where and when techniques
such as RT-PCR could be useful during in vivo
models of infection. The lecture was followed by a
talk by Matthias Klein. After giving a general overview of the distinct pathophysiology of cerebral
infections, he presented results of recent and yet
unpublished studies on the detection of Streptococcus pneumoniae in meningitis, using in vitro experiments and a mouse model of experimental
pneumococcal meningitis. The main focus was on
the role of pathogen recognition receptors in pneumococcal meningitis, targeting TLR2, TLR4, and
TLR9 and their adapter protein MyD88, which
functions as a bottleneck in TLR signalling. He
showed that despite a role of TLR2, TLR4, and
TLR9 for pneumococcal detection in vitro, mainly
TLR2 and TLR4 seem to be responsible in vivo.
Furthermore, he discussed bone marrow chimera
experiments that suggest that especially perivascular cells are involved in the detection of pneumococci during cerebral infection. In the context of
his talk, he demonstrated the use of the protein-array technology in assessing the immune response
in an in vivo model of infection (looking at the protein expression level), which was an important ad-
dendum to the curriculum of the workshop. Davide
Serruto, of Novartis Vaccines, presented how bioinformatic analysis of bacterial genomic sequences
and the application of microarray technology have
significantly advanced our understanding of the
pathogenesis of Neisseria meningitidis. He illustrated how microarray technology has been instrumental to understanding the gene expression profile of N. meningitidis when interacting with host
cells and how FNR regulon analysis improved our
understanding of the ability of meningococcus to
proliferate in oxygen limiting conditions. Moreover, he briefl y showed how genome-based technologies have also the potential to help in the development of a recombinant vaccine against
meningococcal serogroup B. He finished by describing the experimental design and technical approaches he uses to investigate the gene expression
profile of Neisseria in human blood.
Since most of the participants had a background
in the study of antimicrobial drug resistance, two
lectures of the second day focused on this aspect.
Gianni Pozzi of the University of Siena described
the use of real-time PCR for the study of bacterial
populations which carry composite mobile genetic
elements. Due to the mobility of the elements and
the autonomous mobility of parts of the elements,
the observed microbial populations are heterogeneous. In this context a quantitative analysis of elements, target sites, and transposition intermediates
opens entirely new prospects for the study of the
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ESCMID Young Investigator Awardee for Research
in Clinical Microbiology and Infectious Diseases
physiology of these elements and of the microbial
populations carrying them. These observations
gave rise to an interesting discussion at the end of
the presentation. A second lecture related to quantitative analysis in the field of antibiotics was given
by Gian Maria Rossolini, also of the University of
Siena. He presented an overview of the importance
of quantitative gene expression analysis in studying resistance gene functions, antibiotic target
analysis and resistance epidemiology. His talk integrated a technical presentation by Marco Maria
D’Andrea describing the setup of dedicated microarrays to study the epidemiology of beta-lactam
resistance genes.
The audience of the workshop was quite diverse
as documented by the fact that the 43 participants
came from 17 different European countries, i.e.
Bulgaria, Denmark, Estonia, France, Georgia, Germany, Greece, The Netherlands, Italy, Norway,
Portugal, Romania, Slovenia, Spain, Switzerland,
Turkey, and the United Kingdom. With the aim to
facilitate scientific discussions among this diverse
group of young scientists, all participants were invited to present their work in short oral presentations. This offer was enthusiastically accepted by
nearly all workshop participants, with this workshop being for many the first international platform
to present results, and it also allowed presentation
of data in a non-competitive environment. The
presentation subjects varied widely from antimicrobial resistance, bacterial pathogenicity, mycology and virology to quantitative gene expression
analysis. The presentations were an important contribution to the success of the meeting, with regard
to novelty and increasing the opportunity for interaction between faculty and participants.
To complement the theoretical lectures the
workshop was designed to offer two types of practical classes, one on quantitative real-time RT PCR
and one on microarray data management. To permit proficient interaction, three groups of 10 – 14
participants rotated between the microarray class
at the Certosa, the real-time PCR class at the University of Siena and a free afternoon. A dedicated
bus was available to reach the centre of the nearby
town of Siena. For the three microarray data analysis classes held at the Certosa di Pontignano, all
participants used their own laptops and had access
to wireless internet. To give participants the chance
to become acquainted with the software tools used
in the class, a DVD with explanations and software
was sent by regular mail to all participants 3 weeks
prior to the workshop. The bioinformatics classes
were designed to give an overview and hands-on
38
ESCMID NEWS 02/2008
SCIENCE AND EDUCATION
experience on handling massive datasets collected
from microarray gene expression analysis. The
tools that were used were the open source statistical programming platform R combined with packages of the bioconductor project. Overall the participants appreciated getting an overview of the
microarray data mining workflow and gaining insight into statistical procedures of data clustering.
However, due to the heterogeneity of the audience
in regard to prior knowledge in the field of biostatistics, some of the participants reported being
overtaxed. Taking this into account, the bioinformatics classes in the scope of future workshops
should have a more modular setup to address novices as well as advanced data analysts.
The practical classes on quantitative real-time
PCR were held at the LAMMB (Laboratory of Molecular Microbiology and Biotechnology) of the
Dept. Mol. Biol. of the University of Siena. Here
participants had the opportunity to set up dilution
curves in real-time PCR using a Light Cycler with
capillaries and a 480 real-time PCR machine with
96-well plates. Dilution curves were selected as a
wet-lab application, since they are the basis for reaction efficiency testing, evaluation of detection
range, and standard generation in quantitative realtime PCR. While one part of the group set up PCR
reactions, the others attended a lecture on practical
aspects of real-time PCR or another lecture, held
by Laura Mulas, on data analysis in quantitative
real-time PCR. Software presented to the participants was all freely downloadable, as in the microarray classes. The main focus of these presentations was to highlight the importance of the
efficiency of reaction during setup of all experiments. The Relative Expression Software
Tool (REST; www.gene-quantification.de/rest.
html) was described in more detail; it permits efficiency analysis of the reaction.
Altogether the workshop was a great success as
evident from feedback by participants and faculty.
We had three interesting days in the wonderful location of the medieval monastery of Pontignano
and interaction on the workshop topics took place
at a high level. This scientific interaction was not
only limited to a unidirectional transfer of knowhow, but was based upon reciprocal communication about tools and research topics which also
served as a starting point for collaborations between many of us.
Profile of Sylvain Brisse
Susan Aldridge, Medical Writer, [email protected]
Sylvain Brisse’s research is in the area of the phylogenetic diversity and population structure of microbial pathogens, with the
aim of understanding the evolution of virulence, antimicrobial
resistance and other important traits. His work ranges from fundamental aspects of pathogen evolution to practical applications
in taxonomy, molecular identification, and strain tracking. He
applies innovative methods from the field of genomics, such as
multiple gene sequencing and DNA arrays, to the study of bacteria, parasites, viruses and fungi. His main current models are
Listeria monocytogenes, Salmonella enterica, Klebsiella and
Chikununya virus. On the wider phylogenetic scale, he investigates the biodiversity of the Enterobacteriaceae with the aim of
understanding how this heterogeneous family evolved; he is also
interested in the renovation of species definition and taxonomy
and in developing universal sequence-based typing methods.
Sylvain carried out his PhD at the University of Montpellier,
France, on the phylogenetic structure of Trypanosoma cruzi, the
protozoan parasite which is the causative agent of Chagas disease. His molecular identification assays are now widely used to
identify T. cruzi strains at the lineage level. In 1998, he joined
Professor Jan Verhoef at the Department of Medical Microbiology at the University Medical Centre, Utrecht, The Netherlands,
where he undertook research on important nosocomial pathogens such as Klebsiella, Acinetobacter baumannii and Pseudomonas aeruginosa. He is curator of one of the international
MLST websites. He has also played a leading role in the molecular epidemiology component of ENARE (European Network of
Antimicrobial Resistance and Epidemiology).
Sylvain was invited to join the Institut Pasteur, Paris, as a research scientist in 2003. He is Head of the Technological Platform Genotyping of Pathogens and Public Health. Highlights of
his career at the Pasteur Institute include the identification of
Mycobacterium prototuberculosis, the progenitor species of the
tuberculosis bacilli, and the investigation of an explosive outbreak of Chikungunya virus on the French island of La Réunion
in 2006.
Sylvain is Scientific Officer of the ESCMID Study Group on
Epidemiological Markers, which aims at fostering the development of genotyping tools for strain tracking and studies of pathogens populations.
Interview with Sylvain Brisse
Q. Please describe your PhD work on Trypanosoma cruzi and
explain how this advances our understanding of Chagas disease.
A. My research involved, first of all, classifying the natural
strains of T. cruzi found in the wild in South, Central and North
America into six different lineages, using genetic markers to
work out the phylogenetic relationships between them. We found
Ragnar Norrby, Chair of the ESCMID Awards Subcommittee, and Silvain Brisse
after receiving a Young Investigator Award for Research in Clinical Microbiology and
Infectious Diseases during the ECCMID 2008
that the geographic distribution of the lineages is specific and
they have distinct ecological distributions. I also wanted to know
how T. cruzi really evolved. I learned that two of the lineages
were actually hybrids. This evidence of recombination was a
surprise, as it has always been assumed that T. cruzi reproduced
exclusively by clonal binary fission. All this sheds new light on
the pathogenicity of Chagas disease and may help explain why
some people get the intestinal form and some get the cardiac
form – although it is still difficult, as the disease tends to develop
over many years. We also have many more new molecular tools
for identification and diagnosis of T. cruzi infection at the lineage level which I hope will be developed and applied further in
the future.
Q. What is the ENARE group and how did your previous experience in phylogenetics help your work with this project when you
were in Utrecht?
A. ENARE is a project that was concerned with the surveillance
of antibiotic resistance in European hospitals. We gathered a
huge collection of fresh clinical isolates and compared strains
for their antibiotic susceptibility. My mission in integrating the
team was to apply my knowledge of phylogenetics and population genetics to this strain collection. One important goal was to
see whether multi-drug resistant strains spread between countries, which was found to be the case for several pathogens such
as Acinetobacters.
ESCMID NEWS 02/2008
SCIENCE AND EDUCATION
39
Q. You have become a leading expert on Klebsiella. Why is this
species important in public health and what have you learned
about it?
A. Klebsiella is a very important species in nosocomial infection
– second among Gram-negatives only to E. coli as a cause of
bacteremia in European hospitals. It becomes quickly resistant
to new antibiotics, such as the new cephalosporins, and easily
causes outbreaks. So Klebsiella is always of interest to those
concerned with hospital hygiene. Sub-types of K. pneumoniae
also cause a number of infections in the community, including
acute pneumonia and a type of pyogenic liver abscess which is
emerging in Taiwan and elsewhere in Asia. Klebsiella infections
also cause neglected diseases in developing countries, such as
rhinoscleroma or donovanosis. Klebsiella species are very diverse and hard to identify. I began to analyse Klebsiella phylogenetics and found, for instance, several new species among strains
traditionally considered as “K. pneumoniae” – which goes to
demonstrate the complexity of this genus. We have shown that
K. pneumoniae is the origin of the SHV and several other betalactamase families. Parallel evolution of these genes, with the
lineages that harbour them, suggest that these important antibiotic resistance genes have been present in Klebsiella for several
million years.
Q. What tools have you developed or used for studying nosocomial infection and the spread of antimicrobial resistance?
A. We have always used molecular tools. For instance, we developed ribotyping tools in Utrecht; this is a type of fingerprinting
method for comparing strains that relies on genes for ribosomal
RNA. We were validating this as a standard tool for inter-hospital strain comparisons and it did look promising, although it did
not really allow for enough discrimination between strains. Multilocus VNTR (variable number tandem repeat) analysis (MLVA)
is another important tool for molecular typing of strains. We now
mostly use MLST (multilocus sequence typing), which defines
clones based on gene sequences. One of my goals now is to develop universal MLST systems that could analyze many species
at once.
Q. What international collaborations have been/are most important to you in your career to date?
A. My former directors Michel Tibayrenc in Montpellier, Prof.
Jan Verhoef in Utrecht, and Patrick Grimont at the Pasteur Institute have always been supportive of my research and gave me
the necessary freedom to develop my own ideas. Prof. Marc
Struelens in Brussels and Prof. Alex van Belkum in Rotterdam
have also provided important encouragement and have infl uenced my work.
Q. Please describe your work on Mycobacterium protuberculosis and its impact on our understanding of tuberculosis.
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A. Mycobacterium tuberculosis has always been believed to be
homogeneous. It has been hard to find any polymorphisms in
strains identified around the world – therefore it has been a challenge to type TB. We knew there had been a clonal expansion of
the tubercle bacilli about 35’000 years ago, but we did not know
where it came from. Working with Cristina Gutierrez and others
at the Institut Pasteur, I discovered bacilli in Djibouti, East Africa, which were very distinct from classical TB and proved to
be extant strains of an ancestral species. The present strain,
known as the M. tuberculosis complex (MTBC) and which has
been so successful, actually appeared to be a genomic mosaic
resulting from horizontal gene transfer prior to its clonal expansion. Indeed, we could show a lot of genetic recombination between lineages of the ancestral species. We deduced that combination of genomic bits from different lineages has made the
MTBC clone very successful. Further, the amount of synonymous nucleotide variation in housekeeping genes suggests that
tubercle bacilli could have been contemporaneous with early hominids in East Africa. Discovery of the ancestor of TB means we
can look into its genetics and understand why the current strain
is such a successful pathogen in humans.
Q. You also worked on the outbreak of Chikungunya virus in La
Réunion – how did you tackle this problem and what was the
outcome?
A. The outbreak of Chikungunya virus on La Réunion, in the
Indian Ocean, was a public health emergency that emerged early
in 2006. One third of the population was infected, for the first
time in history on this island. No one knew why the outbreak had
become so explosive. The Institut Pasteur, triggered by its National Reference Centre for Arboviruses, decided to look at the
genome of the strains involved. We sequenced the entire genome
of six chosen outbreak isolates as well as sequencing the E1 surface glycoprotein from 127 patients to see if there had been some
shift that could explain the success of the outbreak. We identified
a particular mutation, called E1-226V, which changes a single
amino acid on the surface of the virus so that it becomes more
effective in colonizing the mosquito vector, Aedes albopictus.
The mutated virus multiplies 100 times faster than usual so the
vector acts as a more heavily loaded weapon when it infects peoI]ZZcXdjciZgd[i]Z8]^`jc\jcnV
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replaced the old form within a few weeks and the evolution took
place during the course of the outbreak. This mutation of Chikungunya virus has now been found in other outbreaks in South India and Gabon. This mutation seems to be very beneficial to the
virus and what we are witnessing since 2006 is a good example
of convergent evolution.
Q. Describe your current role and responsibilities at Institut Pasteur please.
A. They are two-fold. I have a research position in the evolutionary biology of microbes, trying to understand large scale evolution and population biology. I am interested in questions such as
how virulence and antibiotic resistance evolve. I also run, together with my colleague Valerie Caro, a service lab dedicated to
genotyping pathogens of public health importance and to carrying out evolutionary studies on populations of pathogens. Given
the concentration of specialists for all sorts of microbes, the Institut Pasteur is a great place to do this sort of work!
Q. Looking back over your career so far, what have been the
highlights and which achievements have given you the most satisfaction?
A. First – my work with T. cruzi, where we discovered very definite lineages that could help explain the clinical forms of the
disease. I am hoping this work will be developed into diagnostic
tools. Then, the discovery of the ancestral form of TB and, finally, the work on the Chikungunya virus which gave our group
a lot of visibility. This was a nice experience and, of course, very
important in terms of public health.
Susan Aldridge, Medical Writer, [email protected]
William Hope’s research is concerned with identifying antifungal dosages and schedules for optimal therapeutic outcomes. He
works in the emerging field of antifungal PK-PD (pharmacokinetics-pharmacodynamics) which explores the relationship between drug exposure and antifungal effect and this is starting to
make an impact on the development of new antifungal agents.
He looks at experimental systems in which the interaction between antifungal compounds, immunological effectors and clinically relevant biomarkers can be defined. Clinical implications
of experimental data are explored with population pharmacokinetics and Monte Carlo simulation techniques. Thereby, dosages
likely to have a therapeutic efficacy can be identified and fed
into clinical trial design.
William did his medical training at the Flinders University in
South Australia, followed by postgraduate training at the Royal
Brisbane Hospital. He then specialized in infectious diseases and
took up a research post at the University of Manchester, UK, in
2002. His work in recent years has focused upon optimizing
therapy for candidiasis and pulmonary aspergillosis. He used
mathematical modelling to investigate combination chemotherapy for C. albicans in a mouse model of infection and then used
Monte Carlo simulation to bridge these results to man. Here he
found that smaller doses of 5-fl uorocytosine and amphotericin B
Q. What will the ESCMID award enable you to do?
A. I want to travel to do some research abroad and learn some
new genomics techniques. Analysis tools evolve so quickly that
there is always something for me to learn. The Award will also
enable me to finance some young scientists to join me for a short
period.
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pergillosis. Typically these drugs might include amphotericin B
deoxycholate, or its lipid formulations, triazoles, such as posaconazole, or the echinocandins, which are a new group of semisynthetic systemic antifungals. The cost of these treatments can
account for a significant proportion of a hospital’s drug budget.
A confocal microscope image
of an alveolar cell layer which
has been invaded by hyphae
(expressing green fluorescent
protein). Macrophages stained
with a red fluorescent dye
are seen interacting with the
hyphae.
could be used together without loss from cell kill, showing that a
less toxic approach to treating the infection is possible. He has
used a similar approach to provide an understanding of the behaviour of micafungin in neonatal candidiasis. Another major
achievement has been the development of a new in vitro model
of pulmonary aspergillosis which will answer vital questions
about this life-threatening infection.
Following positions in the United States at the National Cancer Institute, Bethesda, New York, and the Ordway Research Institute, Albany, New York, William returned to Manchester in
2007 to a permanent position as a Senior Research Fellow.
Q. How did you come to develop an interest in clinical mycology?
A. Mycology is interesting because less is known about fungi
than bacteria and viruses. Fungi are phylogenetically much closer to humans than other microorganisms which means there are
relatively fewer diagnostic and therapeutic targets. I had just
completed my training in infectious diseases and clinical microbiology when I obtained a joint fellowship between Manchester
and the National Institutes of Health with David Denning and
Thomas Walsh both of whom are leading figures in this field.
This gave me the opportunity to learn a wide range of techniques
in clinical mycology.
Q. Why has pulmonary aspergillosis been such an important part
of your work?
A. Pulmonary aspergillosis is important because it is a common
cause of morbidity and mortality in immunocompromised patients. Pulmonary aspergillosis usually affects people with neutropenia and stem cell transplant recipients. The overall mortality is approximately 50 percent. The accuracy of the diagnosis of
invasive pulmonary aspergillosis (IPA) lags behind other infections, where molecular diagnostics such as PCR can be used.
Invasive diagnostic procedures are often precluded in critically
ill patients. The difficulty of diagnosis in aspergillosis leads to
the use of empirical treatments, often involving toxic, expensive
drugs which may be given to those who do not even have as-
42
ESCMID NEWS 02/2008
SCIENCE AND EDUCATION
Q. What are the techniques and tools you use in your work?
A. My main interest is in antifungal pharmacology and how antifungal drugs can best be used. I want to find ways to identify
dosages and schedules that are likely to lead to optimal outcomes. Doing this work in a conventional clinical setting is slow,
so I am interested in using experimental models to speed the
process up. I use population pharmacokinetics which reflects
how a broad range of people will handle a drug. Typically this
will depend upon factors such as age, sex, race and pharmacogenetics, but even after considering these variables, a large amount
of unexplained or residual variance remains. Population pharmacokinetics provides robust estimates of this variance and one can
use these models to understand the behaviour of a drug.
Q. What contribution have you made in candidiasis?
A. I worked with an echinocandin called micafungin, for which
all the clinical efficacy data has been obtained in adults. There is
a condition in premature neonates called haematogenous Candida meningoencephalitis (HMCE) where the fungus invades from
the bloodstream into the brain. With little prior information, it is
difficult to identify the dose of micafungin that should be used in
clinical trials in this patient group. We worked with a rabbit
HMCE model and determined the efficacy of micafungin for this
condition. We then bridged these experimental results to humans. We have been able to describe how the drug behaves in
neonates and use this information to design clinical trials which
are likely to yield meaningful conclusions in the most cost-effective and efficient manner. The dose used in adults is 1 – 2 milligrams per kilo bodyweight, but in neonates we predicted that
one needs a considerably larger dosage of 10 – 15 milligrams per
kilo bodyweight — this is obviously much higher than is intuitively apparent. If we had not known this, and a lower dosage
was used, the clinical trial may have been terminated early because of poor outcomes.
Q. Can you describe the model you have built of the invasive
pulmonary aspergillosis?
A. Aspergillus primarly affects the lung. I developed this model
using Transwell inserts which sit in 24-well tissue culture plates.
The model consists of a semi-permeable membrane with human
alveolar cells grown on top and endothelial cells on the bottom.
Conidia, or spores, are environmentally ubiquitous and inhaled
by humans more or less continuously. The normal immune system prevents germination and the initiation of invasive disease.
In immunocompromised patients conidia escape immunological
surveillance and germinate to form hyphae which invade the
lung and cause tissue damage. It has previously been hard to
build experimental models of this infection because conidia and
hyphae are biologically so different. Our new model is a physiologically faithful mimic of the pathophysiology observed in humans and we can use it to understand characteristics and determinants of fungal invasion. We have demonstrated that most of
the important pathological events occur within the first 24 hours.
It has also been possible to tie the invasion to the kinetics of a
range of clinically relevant biomarkers, such as galactomannan
(a carbohydrate secreted by the fungus) which is increasingly
being used for the diagnosis of IPA. We have had several visitors
in Manchester learning how to make the lung model and I am
hopeful this will facilitate important collaborations in the UK
and in Europe.
Q. In your working life, what is your balance between clinical
and research interests?
A. I provide two clinical sessions each week with patients who
have infectious diseases such as TB and chronic pulmonary aspergillosis. I am about to start a consultation service for solid
organ transplant recipients. There is no evidence that opportunistic infections are abating – perhaps because the number of immunocompromised patients is increasing, and the immunosuppressive treatments are becoming more aggressive. I am
conducting various experimental projects, using both in vivo and
in vitro systems. I am also involved in various clinical trials of
antifungal drugs and am collaborating with others on pharmacokinetic analyses.
A. I would have to say the neonatal candidiasis work because it
has had a direct clinical impact.
Selected references
Hope W, Walsh T and Denning D.
Laboratory diagnosis of invasive
aspergillosis Lancet Infectious Diseases
2005; 5: 609-622
Hope W, Drusano G, et al. Effect of
neutropenia and treatment delay on the
response to antifungal agents in
experimental disseminated candidiasis
Antimicrobial Agents and Chemotherapy
2007; 51: 285-296
Hope W, Seibel N, et al. Population
pharmacokinetics of micafungin
in pediatric patients and implications or
antifungal dosing. Antimicrobial Agents
and Chemotherapy 2007; 51: 3714-3719
Hope W, Warn P, et al. Optimization of
the dosage of fluocytosine in
combination with Amphotericin B for
disseminated candidiasis: a pharmacodynamic rationale for reduced dosing.
Antimicrobial Agents and Chemotherapy
2007; 51: 3760-3762
Hope W and Denning D. Invasive
aspergillosis: current and future
challenges in diagnosis and therapy
Clinical Microbiology and Infection 2004;
10: 2-4
Hope W, Kruhlack M et al. Pathogenesis
of Aspergillus fumigatus and the
kinetics of galatomannan in an in vivo
model of early invasive pulmonary
aspergillosis: implications for antifungal
therapy. Journal of Infectious Diseases
2007; 195: 455-466
Hope W, Mickiene D, et al. The
pharmacokinetics and pharmacodynamics of micafungin in experimental
hematogenous Candida meningoencephalitis: implications for echinocandin
therapy in neonates. Journal of
Infectious Diseases 2008; 197: 163-171
Q. What do you think you will gain from the ESCMID award?
A. I will use the award to support work with others on projects
such as cryptococcal infection which causes meningitis in people with AIDS and which is a big problem in Africa where the
drugs to treat it are not affordable.
Q. What have you learned about the best use of antifungal drugs
in clinical practice?
A. Antifungals are not as prone to resistance as antibacterials
and antivirals. However, Aspergillus resistance is emerging in
the Netherlands and we also have seen this in Manchester. There
are not many antifungal drugs in the developmental pipeline, so
we need to understand how to use the drugs we do have in an
optimal way. I think that we will increasingly need to find ways
to individualize therapy, so that we can optimally treat the patient in front of us rather than using estimates derived from a
population of patients.
Q. Looking back, which of your scientific achievements has
been the most satisfying?
ESCMID NEWS 02/2008
SCIENCE AND EDUCATION
43
Report on Training in a
Foreign Institution
Infections Susceptibility in Senescent
Microglial Cells
Ellen Boelen, Maastricht University Medical
Center, Depts of Medical Microbiology and
Cellular Neuroscience, The Netherlands,
[email protected]
My current research focuses on the correlation between inflammation in microglial cells and neurodegenerative disorders. In the spring of 2008 I visited the laboratory of W. J. Streit at the McKnight
Brain Institute, University of Florida, Gainesville,
for approximately three months to gain specialized
expertise in microglial cell isolation.
Background
Because the population is aging in Western society,
disorders of the elderly, such as neurodegenerative
disorders, are becoming more common. As a result, the most important neurodegenerative disorder, Alzheimer’s disease (AD), is causing significant increases in both morbidity as well as
mortality. Despite extensive research, the cure for
this devastating disease is still lacking. Thus, it is
crucial to gain knowledge about previous events to
better understand disease pathology.
In this regard, the role of inflammation and infection is becoming increasingly recognised. Viruses, such as human immunodeficiency virus
(HIV), herpes simplex virus (HSV) or cytomegalovirus (CMV) and recently also the intracellular
bacterium Chlamydia pneumoniae (Cpn) have
been suggested to contribute to AD. Moreover, infection may possibly be the missing link between
normal aging and the development of a pathological disorder, such as AD.
Microglial cells could play a significant role in
these processes. In previous studies from our lab,
we reported that microglial cells, although rather
resistant to Cpn infection, release several pro-inflammatory cytokines post-infection. The amounts
Isolated microglial cells from old, wild-type C57B16 mice
44
ESCMID NEWS 02/2008
SCIENCE AND EDUCATION
of produced factors were found sufficient to cause
neurodegeneration, one of the hallmarks of AD. As
it has been shown that the activation of microglial
cells coincides with plaque formation, our results
might be key in AD pathology. Likewise, it has already been suggested that microglial cells primed
by aging or by disease will respond differently to
secondary stimuli such as inflammation or infection than microglial cells in a young healthy brain.
This reaction could have an important effect on the
initiation or aggravation of disease.
Therefore, we intended to test the hypothesis
that senescent/diseased microglial cells respond
differently to infection/inflammation, compared to
microglia in a young healthy brain, thereby evoking pathological conditions. To solve these research questions, we planned to isolate microglial
cells from the brain of young, old, and transgenic
AD mice.
The training
Since our lab has no experience in isolating mouse
microglial cells and since the difficulty of performing this technique was confirmed through a literature review, I visited the laboratory of W. J. Streit
to learn how to isolate microglial cells from an
adult mouse brain.
The aim was to set up and optimize this isolation method during the visit. In the end, we were
able to establish an innovative and improved technique to isolate microglial cells, for the first time
from aged mouse brains. By immunofluorescent
staining of microglial cells, astrocytes, and neurons, a 95-98% pure microglial culture could be
confirmed. Moreover, cells were determined to be
viable by trypan blue staining and they could be
maintained for at least one week. Finally, functional properties of microglial cells were also investigated. As such, the uptake of amyloid beta by our
isolated microglia was visualized.
Concerning my research question of whether infection profiles were different for young and aged
primary mouse microglial cells, some pilot studies
were performed. Microglial cells were isolated
with this new method from 2- and 14-month-old
C57Bl6 mice. The cells were cultured and 24 hr
after plating were infected by centrifugation for 1
hr with Cpn at a multiplicity of infection of 1. After 24 hr of additional culturing, the cells were
fixed and stained for Cpn, using a fluorescent antibody directed against the major outer membrane
protein of the pathogen. Preliminary data indicate
that young as well as aged microglial cells can be
infected with the bacteria. Still, the susceptibility
seemed higher in the aged microglial cells. Nevertheless, additional experiments are required to confirm and interpret these results.
Summary
The isolation techniques from the training abroad
will be integrated into my home laboratory to better answer our research question of whether senescent/diseased microglial cells will respond differently to inflammation and infection than young
healthy cells. Also, the impact on hallmarks of AD
has to be investigated. For this reason, future experiments will consist of the isolation of microglia
from young, aged and AD transgenic mice. Next,
these cells will be stimulated with various pathogen-associated molecular patterns (PAMPs) or infected with Cpn for various time periods. In addition, susceptibility of the various microglia groups
to the pathogen, activation markers and inflammatory responses will be compared post infection/inflammation. Finally, the media of the stimulated/
infected microglia will be transferred to a neuronal
cell layer to analyze the incidence of various hallmarks of AD, such as neurodegeneration and amyloid/tau pathology.
A better understanding of these processes will
provide a solid basis for the initiation of new treatment strategies in the future.
4rd Conference on New Frontiers
in Microbiology and Infection
Villars-sur-Ollon,
Switzerland
5 – 8 October 2008
Clostridia: from Old
Diseases to New Threats
More information on
www.escmid.org/conferences.
ESCMID NEWS 02/2008
SCIENCE AND EDUCATION
45
A View into Communicable Disease Control in Malaysia
Report on Training in a Foreign Institution
Stuart Clarke, Visiting Senior Research Fellow,
University of Southampton Medical School, UK,
[email protected]
I am currently undertaking specialist training in
public health. With support from an ESCMID
Training Grant I travelled to Malaysia for a twoweek training stay, which helped to broaden my
experience in preparation for a consultant post and
to better plan for my remaining time in public
health training. Such training also allowed me to
gain exposure in a variety of settings, in which
communicable disease control is practiced.
Objectives of the training
As well as further developing my competency and
consolidating my core skills in the practice of communicable disease control, the international placement was to enable me to develop specific interests
to enhance career opportunities. The placement
should further my credibility both nationally and
internationally at the interface of communicable
disease control, clinical microbiology and academic research.
There are clear benefits in understanding the
systems in other countries and knowing some of
the key people in relation to responding to global
communicable disease issues. It is important for
modern consultants in communicable disease control to have international exposure and understanding given the effect that air travel has on the spread
of communicable diseases. An international placement in Southeast Asia is extremely valuable in
gaining a global perspective.
The training
Malaysia continues to strengthen its public health
system. It is recognized as a developing force in
public health and academic research. Contacts at
the Faculty of Medicine (University of Malaya),
the Institute for Medical Research, and the Public
Health Laboratory, all of which are in Kuala
Lumpur, as well as contacts at the Malaysia campus of the University of Monash were developed
during 2006 due to our complementary interests in
pneumococcal infection and other vaccine-preventable diseases.
I visited various establishments in Kuala
Lumpur and I gave talks at a number of these occasions. During my visit I learnt about the public
health system, communicable disease control, and
also built upon my existing academic contacts.
46
ESCMID NEWS 02/2008
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Background
Malaysia is a developing nation. Although its cities
host leading financial institutions in the region,
there are huge issues surrounding the health of the
population. The world’s tallest twin towers sit in a
city where there are high levels of poor health.
In 2006, the population of Malaysia was 26.64
million with an average annual growth rate of 1.9.
The state of Selangor has the highest resident population of 4.9 million. Malaysia has a young population (42% are under the age of 20 years) whilst
the working population totals some 16.9 million
(15 to 64 years of age). There is an almost equal
gender split (50.9% to 49.1%, male to female). The
crude birth rate and crude death rate were 18.7 and
4.5 per 1’000 population, respectively. Life expectancy at birth for males was 71.8 years and 76.3
years for females (compared to 56 years and 58
years in 1957).
There were 1’905’089 hospital admissions during 2006. The Ministry of Health uses these statistics for determining levels of morbidity and mortality. Normal childbirth was the most common
cause of hospitalization (14.91%) followed by
complication of pregnancy, childbirth and the puerperium (12.39%). Diseases of the respiratory
system and circulatory system accounted for 7.3%
and 7.26% of admission, respectively. Cancer is
reported infrequently (3.13%). Of the 40’586
deaths in Ministry hospitals, septicaemia was the
most common (16.87%), followed by heart and
circulatory diseases at 15.7%. Pneumonia accounted for 5.81% of deaths.
Communicable Disease Control
The Disease Control Division of the Ministry of
Health plays an important role in the prevention
and control of diseases. Its remit includes communicable and non-communicable diseases. It therefore has a role in health promotion. I met with officials from the Communicable Disease Section.
Some infectious diseases are notified under the
Prevention and Control of Infectious Diseases Act
1988; these include cholera, typhoid, food poisoning, hepatitis A and dysentery. Notification of other
infectious diseases occurs by syndrome rather than
specific infection. For the latter, there were 25 notifications from three hospitals in 2006. Acute respiratory syndromes accounted for twenty of these.
In 2006, there was no polio and the incidence of
whooping cough, neonatal tetanus and diphtheria
remain at less than 1 per 100’000 population. Measles has decreased from 5.39 per 100’000 population in 2005 to 2.27 in 2006. Hepatitis B has also
Institute of Medical Research, Kuala Lumpur
Prof. Shamala, other academic staff and students from the Dept. of Microbiology
at the University of Malaya Medical School
decreased, from 5.69 per 100’000 population in
2005 to 4.67 in 2006.
Cholera, typhoid/paratyphoid, hepatitis A and
dysentery continue to decline. Apparently, the incidence of food poisoning is low. Only 6’938 cases
(incidence rate of 26.04 per 100’000 population)
were reported during 2006 but the numbers fluctuate from year to year.
Influenza surveillance was strengthened in 2004
due to the prospect of pandemic influenza. It is
monitored via an influenza-like illness sentinel
surveillance system using consultation rate as its
indicator. It is carried out in 246 government and
private clinics and hospitals throughout the country. The consultation rate remained below the
threshold of 1.0 per 100’000 population throughout 2006 (as for 2004 and 2005). Malaysia has a
National Influenza Pandemic Preparedness Plan
which was launched in January 2006. A table-top
exercise was conducted in April 2006, an exercise
took place at Kuala Lumpur International Airport
in September 2006, and a regional pandemic response exercise was organized in June 2007.
There has been a year on year increase in dengue cases although, in 2006, there was a decrease
to 38’556 cases (144.7 per 100’000 population).
Of these, 94.6% were dengue fever with the remainder being dengue haemorraghic fever. However, only 47.3% of all cases were confirmed.
Malaria continues to decrease. There were 5’294
cases (19.9 per 100’000 population) in 2006 as
compared to 5’569 cases in 2005. Most cases occur
in Sabah (57.2%) and Sarawak (26.7%) on East
Malaysia. Of all cases, 40.1% were in foreigners.
Malaysia has an intermediate TB burden. In
2006, there were 16’665 new cases registered of
which 10’274 were infectious. The incidence rate
(all forms) is 62.6 per 100’000 population.
The cumulative total of HIV cases between
1986 and 2006 is 76’389. In 2006, there were
ESCMID NEWS 02/2008
SCIENCE AND EDUCATION
47
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HiV^c^c\BZi]dY
5’830 new infections reported. Of these, 75% were
contracted through needle sharing.
Malaysia has a large population of foreign
workers. The population is medically examined
and those deemed “unfit” are not allowed to renew
their work permit. Infectious diseases found
amongst this population in 2006 included hepatitis
B (33.5%), abnormal chest X-ray indicative of TB
(23.3%) and syphilis (8.7%).
Disease surveillance also occurs amongst Hajj
pilgrims. In the 2006 pilgrimage there were 54 reported deaths, the main cause being heart attack
(18 deaths), followed by septicaemia (5 deaths),
lung infections or pneumonia (3 deaths) and others
(28 deaths).
The Infection Control Unit of the Ministry of
health was established in 2002. It systematically
monitors hospital-acquired infection and develops
infection control policy. A point prevalence study
has been conducted in 14 state hospitals and three
university hospitals each March and September
since 2003. According to this study, the prevalence
of hospital-acquired infections has decreased from
7.4% in March 2003 to 3.54% in September 2006.
MRSA surveillance is conducted monthly with an
apparent downward trend of 0.35% in 2003 to
0.25% in 2006. ESBL rates are below 0.5%.
>̈œ˜>Ê*ÕLˆVÊi>Ì…Ê>LœÀ>̜ÀÞ
The National Public Health Laboratory (NPHL)
was set up to provide specialist reference laboratory services for government hospitals. The laboratory received 4’744’026 clinical and 3’895 food
and environmental samples in 2006. These samples were processed for the purposes of diagnosis,
surveillance and outbreak investigation. The workload is limited at the moment as the respective
roles of the NPHL and Institute for Medical Research (IMR) are being finalized.
˜Ã̈ÌÕÌiÊvœÀÊi`ˆV>Ê,iÃi>ÀV…
The IMR is a government institution that undertakes medical research of national priority. Its
budget in 2006 was RM38 million and it has 671
positions (of which 544 are filled). There are 52
ongoing projects and, in 2006, there were 58 scientific papers and 13 reports published. The centre of
personal interest is the Infectious Diseases Research Centre (IDRC), which has Bacteriology,
Entomology, Parasitology and Virology Units. The
units focus their research on the molecular diagnosis and transmission of infectious diseases. The
overall role of the IMR is being discussed since,
currently, it has some remit for typing of bacteria
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and viruses, and also for investigating outbreaks.
However, with the developing of the NPHL, the
IMR will have a more research-focused role.
Niels Hø iby, Department of Clinical Microbiology, Rigshospitalet, University of Copenhagen,
Denmark, [email protected]
-Փ“>ÀÞ
The international placement fulfilled all its aims. I
gained a good knowledge of the health systems in
Singapore and Malaysia, and more specifically a
good understanding of the public health systems.
Due to my personal interests, I also gained an excellent overview of the arrangements for communicable disease control in each country. I also had
the opportunity to build on my existing academic
collaborations with clinical and academic microbiologists and infectious disease consultants in
Singapore and Kuala Lumpur. These collaborations will continue to develop over time.
I gave numerous presentations to a broad audience and also further developed my competency in
numerous areas as planned.
Hans Christian Joachim Gram (1853 –1938; Fig. 1)
was the first child of professor of law, Frederik T.J.
Gram, and his wife Louise. He graduated in 1871
from the Metropolitanskolen. His father died when
Christian was 18 years old and according to tradition at that time, Christian became responsible for
his family although his six brothers and sisters
were still children and he himself had not finished
his education (1, 2).
Initially he studied natural science (botany) at
the University of Copenhagen and became an assistant to professor of zoology Jaspetus Steenstrup
(1813 – 97) at the zoological collections of the University. Steenstrup convinced Gram to study medicine which he himself had done, but Gram also
continued to work with botany at Eugen Warming’s (1841 – 1924) laboratory, who had published
the first Danish bacteriological paper in 1876 (35). During his medical study, Gram and his fellow
students admired the novel bacteriogical work of
Carl Julius Salmonsen (Fig. 2) who worked as a
young medical doctor at the Kommunehospital in
Copenhagen and later became professor of general
pathology (bacteriology) (4, 5). His knowledge of
botany, microscopy and natural science was highly
advantageous and decisive for Gram’s career (3).
After he switched from the study of botany to medicine, he graduated as a medical doctor in 1878.
His clinical training was undertaken at the Kommunehospital in Copenhagen (2, 3). In 1882 he received a gold medal from the University for a scientific paper and continued his research which was
accepted as a doctoral thesis, Investigations of the
size of erythocytes in humans, in 1883. This became a highly cited standard for this topic for many
years since his measurements were very precise
and because he described the increasing size of
erythrocytes in pernicious anaemia and jaundice
(2, 3).
Gram’s wife Louise (1865 – 1900) became
chronically ill and died of tuberculosis when their
two boys were 3 and 10 years old, but Christian’s
three unmarried sisters, “the aunties”, volunteered
to keep house and bring up the children (1). Gram
was deeply infl uenced by the death of his wife and
socially isolated himself after that time but worked
even harder than before. He enjoyed travelling and
had a summer house “Siesta” in Alsgarde in North
Zealand (1). One of Christian’s grandchildren remembers that he was a snappy old man (Fig. 4) but
Ê
he had a very good relationship to his granddaughter (1, 6). He was a cheerful person when he was
younger. Many members of the Gram family held
prominent positions in the Danish administration
and in the universities. For example, his sons Hans
Christian J. Gram (1890 – 1955) and Kai Gram
(1897 – 1961) (Fig. 3) were professors of internal
medicine and botany, respectively; his grandchild
Christian Gram (b. 1932) was professor of computer science and his great-grand daughter Lone
Gram (b. 1960) is professor of microbiology.
The Danish pioneer of bacteriology, Carl Julius
Salomonsen (1847 – 1924) obtained the first European university chair of medical bacteriology and
became head of the Laboratory for Medical Bacteriology in 1883 (Fig. 2) at the University of Copenhagen (5) and his task was to organize laboratory courses of bacteriological techniques. The first
course took place in the spring (3 months) and autumn (2 months) of 1883 in the museum of botany
and Christian was among the eleven participants
(5). Gram had planned to visit famous bacteriologists in other countries after finishing the course
and Salomonsen gave him a letter which introduced him to the pathologist Carl Friedländer at
Friedrichshain’s Hospital in Berlin. Salomonsen
knew Friedländer from his own visit to Robert
Koch in 1882 (7).
Gram arrived at Friedländer’s laboratory on 22
October 1883 and worked in his laboratory until 20
March 1884 (7). Several staining methods were
available for bacteriology at that time, but when
they were applied on tissues from infected organs
both bacteria and nuclei from the cells of the patients or the experimental animals were stained. It
was therefore difficult to distinguish bacteria from
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Figure 1. Christian Gram
as a young man
50
ESCMID NEWS 02/2008
Figure 4. Christian Gram
after he had retired
Figure 2. Carl Julius
Salomonsen 1883, pioneer
Danish bacteriologist
nuclei in the tissue cells. Friedländer studied the
aetiology of pneumonia and he had detected capsulate bacteria in autopsies from patients who had
died of pneumonia (6, 7). Gram had already worked
on the development of a combined staining method
for sliced samples from kidneys. He employed aniline-gentiana violet and iodine solution to obtain
blue nuclei and brown urinary cylinders. The aniline-gentiana violet stained samples were usually
difficult to decolorize by ethanol but when he added iodine solution after the aniline-gentiana violet
staining, the samples became completely decolorized by ethanol. This observation was the background for Gram’s development of his famous
staining method in which pneumococci, the common causative agents of pneumonia, became more
intensively stained than by any of the other staining methods whereas nuclei and other tissue components became completely decolorized by ethanol. It was in fact the first method which stained
bacteria but not nuclei (7). The time needed for
Gram’s staining method was 15 min for ordinary
bacteria but 12 – 24 h for mycobacteria. Gram employed staining with Ehrlich’s aniline-gentiana violet (or fuchsin) followed by Lugol’s iodine solution in water (as mordant), which at that time was
frequently used by bacteriologists for staining of
specimens.
Gram observed that a number of different bacteria were stained black-reddish (Fig. 5) whereas
other e.g. typhoid bacteria were decolorized, but
that they (and the tissue components) could be visualized by counterstaining with e.g. Bismarck
brown or vesuvin. Gram’s staining method has
only been slightly modified since 1883 and the current modification employs crystal violet followed
by iodine solution in water, decolourization with
ethanol, and counterstaining with fuchsin. The procedure can be completed in 3 min.
The significance of Gram’s staining method became immediately clear to him since he noticed
severe errors in Friedländer’s interpretation of the
aetiology of pneumonia, mixing up the pneumo-
cocci observed by microscopy with the Klebsiella
pneumoniae (later called Friedländer’s bacil) he
cultured from the patients and used for animal experiments (7). Gram was therefore very hesitant to
criticize Friedländer’s work publically because it
would support his opponent Albert Fraenkel
(1848 – 1916), who cultured the pneumococci and
used them for animal experiments (later called
Fraenkel’s pneumococci) (7). The publication of
Gram’s method was therefore slightly delayed (15
March 1884; 7, 8). There is little doubt that he realized the importance of his staining method (7, 8)
and it was also recognized by the scientific community because it allowed categorizing bacteria in
two large, unrelated groups, Gram-positive and
Gram-negative, with crucial implications not only
for identification of bacteria and taxonomy, but
also as a rapid diagnostic tool in the daily work in
bacteriological laboratories all over the world. This
was further internationally acknowledged by a
public demonstration in the Academy of Science in
Paris in 1886 by Emile Roux (1853 – 1933) from
Institut Pasteur, who used Gram’s staining method
to identify gonococci (3). The universal use of
Gram’s staining method means that Gram probably
still is the name which is used most frequently in
bacteriology laboratories and elsewhere every day
all over the world.
The biochemical and structural background for
the Gram-differential staining method was explained in 1929 by V. Burke and M.W. Barnes as
due to differences in the permeability of the cellwalls but the current explanation was published by
M.R.J. Salton in 1963 (9, 10), who showed that the
thick peptidoglycan layer of Gram-positive bacteria is responsible for the differentiation since it is
dehydrated by ethanol and that causes trapping of
the crystalviolet-iodine complex in the small pores
of the peptidglycan. In contrast, ethanol extracts
lipids from the outer membrane of the Gram-negative bacteria and thereby increases the permeability
of the thin peptidoglycan layer (9, 10).
Gram also published his staining method as an
SCIENCE AND EDUCATION
oral presentation at the International Congress of
Internal Medicine in Copenhagen in August 1884
where Salomonsen was secretary. Gram sent a
printed version of his presentation to Salmonsen in
July 1884 and it was published in the final programme and later in the proceedings from the congress (11). Gram did not continue his bacteriological research but published pharmacological and
clinical studies on diuretics and temperature-lowering drugs. He left bacteriology and became professor of pharmacology at the University of Copenhagen (1891 – 1900) and in 1892 he also became
physician-in-chief at the department of internal
medicine A at Frederik’s Hospital, which subsequently changed its name to Rigshospitalet. He
was a very thorough and systematic clinician who
was much loved by his patients and respected for
his noble and upright personality by his assistants
to whom he was at the same time an authoritative
teacher and a good friend (3). In 1893 he became
professor of internal medicine and subsequently
physician for the Danish king and the royal family
until he retired at the age of 70 in 1924. In 1902 – 09
he published his lectures for students and he also
authored chapters on parasitic worms in Nordic
Textbook of Internal Medicine (3). He had a private clinic in Copenhagen and held important positions in the national health board. He became honorary member of the Danish and foreign scientific
societies and was doctor honoris causa at the University of Kristiania in Norway (2). Gram smoked
cheroots and he was treated successfully by irradiation for cancer of the larynx after he had retired
but he still continued smoking (1). When he died
there were numerous obituaries in Danish and international scientific journals (3).
One-hundred years after publication of Gram’s
staining method, his grandson Niels F. Gram
(1927-2001) was invited to the annual meeting of
the Latin American Society for Clinical Parasitology in Caracas, Venezuela where the president of
the Society, Dr Jose J. Gutierrez Alfaro, published
his book Hans C.J. Gram medico que marco epoca
con su famoso metodo de coloracion (6). Not many
other Danish physicians have achieved a similar
and durable fame - and it was based on only one
publication and a few months of work!
References
1. Høiby N. Interviews 2007
of Gram’s granddaughter Anne
Louise Fløystrup
(1922 – 2007) and his
grandson Christian Gram (b.
1932) and access to written
family information and pictures
and photos of Prof. Gram
Julius Salomonsen,
1883 – 1884. ASM News 47:4449; 1981. Abbreviated from:
Lautrop H. Christian Gram and
his staining method with
unpublished letters from Gram
to Salomonsen 1883-84.
Bibliotek for læger 174:1-30;
1982
2. Engeltoft P, Fenger, VA(eds.).
Den Danske Lægestand
1936 – 1949 (Danish
Physicians), 12:222-23; 1949
3. Sonne, C. Christian Gram
born Sept. 13th, 1853 – died
Nov. 14th, 1938. Acta Medica
Scandinavica. XCVIII, fasc. VI, p.
441-43; 1939
4. Lautrop H. Carl Julius
Salomonaen og bakteriologiens
begyndelse i Danmark.
Bibliotek for læger 175:97-146;
1983
5. Lautrop H. Den første
europæiske lærestol i
medicinsk bakteriologi oprettes
ved Københavns universitet i
1883. Bibliotek for læger
175:147-95; 1983
6. Gram NF. Latinamerikansk
hyldest til Christian Gram.
Medicinsk Forum 41:89-93;
1988
7. Lautrop H. Christian Gram on
the Gram stain in letters to Carl
Figure 5. Gram staining of Spingomonas
panucimobilis from blood culture. Gram’s
original smears do not exist.
(x1000, photo by E. Nagy)
8. Gram C. Ueber die isolierte
Färbung der Schizomyceten in
Schnitt- und Trockenpräparaten. Fortschr. Med. 2:135-139;
1884
10. Beck RW. A chronology
of microbiology in historical
context. ASM Press,
Washington DC, 2000, pp. 105,
175, 261
11. Gram C. Ueber die Färbung
der Schizomyceten in
Schnitttpräparaten. ComptesRendue, Section d’Anatomie,
Pathologie et de Pathologie
Generale. 8me session, Tome 1,
p. 116-17; 1886. Congress
Periodique Int. Sciences
Medicale
9. Lechevalier HA. Solotorovsky, M. Three centuries of
microbiology. Dover
Publications, New York, 1974, p.
136-38
ESCMID NEWS 02/2008
SCIENCE AND EDUCATION
51
Making Sense of Microbial Typing for Infection
Control: ESGEM and the New Guidelines
Barry Cookson, Director of Laboratory of
Heatlhcare Associated Infection, Health
Protection Agency and Treasurer of ESGEM
For details of ESGEM please visit www.escmid.
org/esgem or contact Alexander Friedrich,
Secretary of ESGEM (alexander.
[email protected])
Molecular typing is now an essential component of
microbiology and of infection control services provided across Europe and in many other countries
of the world. Recent quantum advances in comparative genomics have yielded a wide choice of
powerful methods for studying the genomic relatedness of microbes. The epidemiology of microorganisms does not recognise national boundaries.
Collaboration between scientists working in different countries is therefore essential to standardize
methodology and to track the spread of particular
virulent or resistant microbial pathogens.
ESGEM is a group of ESCMID members who
share an interest in epidemiological typing systems. The Study Group first wrote consensus
guidelines to optimize the use and evaluation of
microbial epidemiologic typing systems in 1996
(1) following extensive consultation within the
group. Until that time there was no agreement as
how best to assess and utilize microbial typing approaches to explore epidemiological hypotheses.
The scientific literature was of varied quality. Since
their publication, the guidelines have been quoted
frequently. The principles have been used in many
scientific papers describing new typing approaches
or how best to use typing methods to explore epidemiological hypotheses related to hospital and
community outbreaks. They are also of use in studies to evaluate the success or otherwise of interventions to prevent or control healthcare-associated and community infections (2).
Since these guidelines were written there have,
of course, been numerous innovations and improvements in existing technology and analytical
approaches, together with an astronomical improvement in our understanding of microbial genomes, as well as extensive discussion on how typ-
52
ESCMID NEWS 02/2008
SCIENCE AND EDUCATION
ing results should be interpreted to assign isolates
to types. ESGEM thus decided to update the guidelines. The updated guidelines (3) describe new and
old phenotypic and genotypic methods for typing
all clinically relevant bacterial species, their underpinning principles, advantages and disadvantages. Criteria for their evaluation, application, and
– very important for everyday practice in many
laboratories, especially for PFGE and PCR-based
methods, where divergent views had been expressed so far – interpretation of their results are
also proposed with an extensive glossary of terms
that many will find useful for teaching purposes.
Finally, the issues of reporting, standardization,
quality assessment, and international networks are
discussed. We anticipate that the current guidelines
will be as popular as their predecessors and serve
as a reference point for many scientists around the
globe. Please see www.escmid.org/guidelines for
the full version of the guidelines.
1. Struelens MJ and members of the European
Study Group on Epidemiological Markers (ESGEM) of the European Society for Clinical
Microbiology and Infectious Diseases. Consensus guidelines for appropriate use and evaluation of microbial epidemiologic typing systems.
Clin Microbiol Infect 1996; 2: 2-11
2. Stone SP, Cooper BS, Kibbler CC, Cookson BD,
Robert JA, Medley GF, Duckworth G, Lai R,
Ebrahim S, Davey PG, Brown EM, Wiffen PJ.
The ORION statement: guidelines for transparent reporting of outbreak reports and intervention studies of nosocomial infection. Lancet Infect Dis 2007; 7:282–88 and J Ant Chemother
2007; 59: 833-840
3. van Belkum A, Tassios PT, Dijkshoorn L,
Haeggman S, Cookson B, Fry NK, Fussing V,
Green J, Feil E, Gerner-Smidt P, Brisse S,
Struelens M, for the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group on Epidemiological Markers (ESGEM). Guidelines for the validation and
application of typing methods for use in bacterial epidemiology. Clinical Microbiology and
Infection 2007; 13 (s3): 1-46
CLASSICAL MICROBIOLOGY
GRAM STAINING &
MICROSCOPY
CLINICAL MATERIAL
HOST TESTING : ANTIBODIES
ANTIGEN TESTS:
ELISA
MONOCLONALS
NUCLEIC ACIDS :
DNA PROBES
DNA AMPLIFICATION
DNA SEQUENCING
PREDICT
PREVENT
PERSONALISE
IN SITU
DNA
HYBRIDISATION DIAGNOSTICS
HOST
RESPONSE
RATIONAL THERAPIES
AND EPIDEMIOLOGICAL
SURVEILLANCE
PREPARATION
FOR CULTIVATION
SOLID
MEDIA
LIQUID
ENRICHMENT
CULTURE
SIMPLE TESTS FOR CATALASE
ACTIVITY, INDOL SPOT TESTS,
CAPSULE STAINING, MOTILITY ETC
SPECIES IDENTIFICATION :
(AUTOMATED) ENZYMOLOGY & BIOCHEMISTRY
ANTIBIOTIC SUSCEPTIBILITY TESTING
EPIDEMIOLOGAL ANALYSES :
CLASSICAL :
PHAGETYPING
SEROLOGY
ANTIBIOGRAM
MOLECULAR :
DIFFERENTIAL AMPLIFICATION
RFLP ANALYSIS
SNP DETECTION
SEQUENCING
BIOPHYSICS
BIOCHEMISTRY &
‘’OMICS’’ TECHNOLOGIES
SYSTEMS BIOLOGY
ESCMID NEWS 02/2008
SCIENCE AND EDUCATION
53
GRACE and ECCMID
Roger Finch, on behalf of GRACE WP12,
r.fi[email protected]
The GRACE Network of Excellence (www.grace-lrti.org) includes among its collaborating partners two leading European
Societies – ESCMID and The European Respiratory Society
(ERS). These Societies have within their portfolio of activities
two key components of the GRACE project, namely antimicrobial resistance and lower respiratory tract infections. This partnership creates both opportunities for collaborative research and
an effective and successful arrangement for the educational and
training outputs of GRACE.
ESCMID and ERS have enthusiastically supported the programme of GRACE Postgraduate Courses (PGCs) and Workshops (WSs). PGCs have preceded the ECCMID Congresses
held in Munich in 2007 (second PGC) and in Barcelona this year
(fourth PGC). The first and third GRACE PGCs were held in
conjunction with the ERS Congresses in 2006 and 2007 which
will also host the fifth PGC later this year.
The recent PGC in Barcelona highlighted the healthcare burden of LRTI in Europe, looking at antibiotic use and resistance,
morbidity and mortality in both primary care and hospital care,
the socioeconomic considerations, and disease prevention by
vaccine use. This programme was complemented with data from
the GRACE Workpackage (WP)8 on attitudes of doctors and patients and from WP9/10 on the observational and interventional
studies which are now underway in the GRACE primary care
network. The PGCs and WSs are the building blocks of a broadly based curriculum designed by GRACE WP12. Over the fiveyear period of funding available to the GRACE PGCs and WSs,
many of the important areas of knowledge relevant to the science and practice of antimicrobial resistance, lower respiratory
tract infections and genomics of man and microorganisms will
be covered. These are captured within the GRACE objectives
and highlight new research information from the project.
Delegates have given high approval ratings for the PGCs to
date. It is therefore important to emphasize that the outputs of
these events are freely available online at the GRACE e-learning
portal (www.ersnet.org/grace) which can also be accessed
through the ESCMID and ERS websites. Thus the “delegate”
base for GRACE education and training activities is very much
greater than those professionals who have attended the courses
in person.
Erratum
We regret that in the last issue
of ESCMID News(1/2008, p.
32), we gave the incorrect
publishing information for the
book, The Microbiological
Safety of Food in Healthcare
Settings. The correct
54
ESCMID NEWS 02/2008
Forthcoming Events
For the next ECCMID in Helsinki in May 2009, a sixth PGC
– now called an “Educational Workshop” to be consistent with
the nomenclature of the ECCMID educational events – has been
developed and will focus on “Challenge and Change in Pneumonia” with features on two key community pathogens, namely
Streptococcus pneumoniae and community-associated-MRSA.
The introduction of conjugate pneumococcal vaccine in Europe
is likely to bring about significant changes to the impact of pneumococcal disease as uptake of the vaccine extends across the
Continent. By way of contrast, community-acquired MRSA has
yet to make a significant impact in Europe but from experience
across the Atlantic, it is a truly devastating illness on the occasions it affects the lungs.
Some more good news from the collaboration between
ESCMID and GRACE is that in addition to the PGC there is to
be an ECCMID Symposium in Helsinki co-organized by
ESPRIT and GRACE. ESPRIT is one of the Society’s expert
groups, and stands for the ESCMID Study Group for Primary
Care Topics.
Finally, the inclusion of two posters in the European Network
Corner at the recent ECCMID provided a further opportunity for
GRACE to share its research programme and educational outputs with delegates attending the Congress. This is another example of how GRACE benefits from the strong support it receives from ESCMID and in particular Javier Garau who is not
only a member of the ESCMID Executive Committee but is also
a member of the GRACE WP12 Education and Curriculum
Committee.
More detailed information
about ESCMID courses and
conferences as well as general
information about other events
can be found on the ESCMID
website (www.escmid.org)
under Courses & Workshops,
ECCMIDs & Conferences, or
Calendar of Events.
ESCMID Events
18 – 20 September 2008
3rd GRACE Workshop
The Science, Practice and Challenges of Lower
Respiratory Tract Infections in Primary Care
Cambridge, UK
4 October 2008
5th GRACE Postgraduate Course
Antibiotics or Not: from Acute Bronchitis to
Acute Exacerbation of Chronic Bronchitis
Berlin, Germany
7 – 10 May 2011
21st European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) / 27th
International Congress of Chemotherapy (ICC)
Milan, Italy
Endorsed by ESCMID
5 – 9 October 2008
ESCMID / FEMS Conference on New Frontiers
in Microbiology and Infection
Clostridia: from Old Diseases to New Threats –
Basic Science Meets Infectious Diseases
Villars-sur-Ollon, Switzerland
23 – 24 January 2009
14th International Symposium on Infections in
the Critically Ill Patient
Berlin, Germany
[email protected]
www.infections-online.com
9 – 10 October 2008
Moving Forward in Cooperation
ESCMID Professional Affairs Workshop
Rome, Italy
13 – 16 February 2009
International Meeting on Emerging Diseases
and Surveillance (IMED 2009)
Vienna, Austria
[email protected]
http://imed.isid.org
5 – 7 November 2008
ESCMID Postgraduate Education Course
Invasive Fungal Diseases: Epidemiology,
Diagnosis, Therapy and Antifungal Susceptibility Testing
Nijmegen, The Netherlands
8 – 11 November 2008
ESCMID/SHEA Hospital Epidemiology
Training Course
Oisterwijk, The Netherlands
Roger Finch as Chair and Javier Diaz Domingo addressing questions
from the delegates
10 – 13 April 2010
20th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID)
Vienna, Austria
19 - 22 October 2009
Clostridia: The Impact of Genomics on
Disease Control
Rome, Italy
[email protected]
www.clostridia.net
16 – 19 May 2009
19th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID)
Helsinki, Finland
information should read as
follows:
Edited by: Barbara Lund
and Paul Hunter, 400 pages,
24 illustrations. Blackwell
Publishing, GBP 105.00.
SCIENCE AND EDUCATION
ESCMID NEWS 02/2008
SCIENCE AND EDUCATION
55
ESCMID’s mission is to improve the diagnosis, treatment
and prevention of infectious diseases by promoting
and supporting research, education and training in the
infection disciplines. This is achieved by scientific
exchange, educational programmes, grants and awards,
certification and consultation with professional and
government agencies.
Front Page: Christian Gram, who developed the Gram stain, and his two sons Kai
Gram (left) and Hans Christian J. Gram
(right) in front of the Rigshospitalet,
Copenhagen, where he was physician-inchief of the Department of Internal
Medicine A. This year marks the 125-year
anniversary of the Gram stain.
ESCMID e.V.
Hainbuchenstrasse 65
P.O. Box 1131
DE-82018 Taufkirchen
Gemany
[email protected]
www.escmid.org
Below: The ESCMID Presidents (past,
current and elect) took the stage
and posed for a group picture after the
past presidents received memorial
plaques during the Opening Ceremony at
the 18th ECCMID 2008 in Barcelona.
From left to right: Ragnar Norrby (2005 –
2007), Marc Struelens (2003 – 2005),
Roger Finch (2001 – 2003), Carl Erik Nord
(1999 – 2001), Michel Glauser (1997 –
1999), Ian Phillips (1995 – 1997),
Giuseppe Cornaglia (2007 – 2009),
Jacques Acar (1993 – 1995), Evelio Perea
(1990 – 1993), Jan Verhoef (1983 –
1990), Javier Garau (2009 – 2011)