GENOMICS TO COMBAT RESISTANCE AGAINST ANTIBIOTICS IN COMMUNITYACQUIRED LRTI IN EUROPE GRACE

1
GENOMICS TO COMBAT RESISTANCE AGAINST ANTIBIOTICS
IN COMMUNITY-ACQUIRED LRTI IN EUROPE (GRACE)
H. Goossens (Coordinator), K. Loens (Manager), M.
Ieven (Lab. Network Support), S. Coenen (PC
Network Support), T. Sterckx (Administrator) www.
grace-lrti.org
GAPS IN KNOWLEDGE ON CA-LRTI
POTENTIAL APPLICATIONS

• Behaviour and expectations of doctors and
  patients?
• Aetiology?
• Diagnostic strategies?
• Prediction of poor outcome?
• Treatment?
• Cost-effectiveness?
• Potential of genetics to enhance clinical care?

• Novel rapid genome based diagnostic tests for the
  detection of pathogens implicated in
  community-acquired LRTI.
• A European repository of specimens and strains
  linked to a database including microbial and
  patient information.
• Risk factors for infection with resistant S.
  pneumoniae and H. influenzae in patients with
  community-acquired LRTI.
• Pneumococcal genes important for virulence and
  for antibiotic resistance development.
• Optimal pneumococcal treatment and prevention
  strategy linked to severity of community-acquired
  LRTI.
• Human susceptibility genes affecting severe
  community-acquired LRTI.
• Potential human target pathways for new
  immunomodulatory approaches.
• Potential genetic risk profiles for various
  presentations and outcomes of community-acquired
  LRTI in several European populations.
• Evidence-based definitions of the major
  community-acquired LRTI.
• Clinical outcome measures for evaluating
  interventions.
• Clinical models to differentiate viral from
  bacterial infections and identify pneumonia.
• Clinical models to identify patients at risk for
  adverse outcomes including severe and prolonged
  illness.
• Subgroups of patients with community-acquired
  LRTI which benefit and which do not from
  antibiotic treatment.
• Practice based intervention in reducing
  inappropriate antibiotic use and resistance in
  patients with community-acquired LRTI.
• Cost-effectiveness of the management strategies
  developed in the observational and intervention
  studies.
• A model for the macroeconomic impact of
  antibiotic resistance and policies to contain
  resistance.
• Economic evaluations of molecular diagnostics.
• Educational packages to inform postgraduate
  lifelong learning needs of prescribing
  professionals.

ABSTRACT
GRACE is a Network of Excellence focusing on the
complex and controversial field of
community-acquired lower respiratory tract
infections (LRTI), which is one of the leading
reasons for seeking medical care. The promiscuous
use of antibiotics to treatment of LRTI accounts
for a major part of the community burden of
antibiotic use and contributes dramatically to
the rising prevalence of resistance among major
human pathogens. The overall objective of GRACE
is to combat antimicrobial resistance through
integrating centres of research excellence and
exploiting genomics in the investigation of
community-acquired LRTI. Microbial and human
genomics will be integrated with health sciences
research consisting of clinical observational and
intervention studies, health economics and health
education to specifically change practice in
managing community-acquired LRTI. In the jointly
executed research programme, 17 academic groups,
spread widely across 9 EU Member States and 5
SMEs will participate. GRACE will organise
professional education, including web-based
teaching and practical courses, through two
leading European scientific societies (European
Society of Clinical Microbiology and Infectious
Diseases and European Respiratory Society) to
disseminate the excellence of the programme. A
high level of co-ordination will be obtained
through a professionally IT-supported and
rigorous management structure. The network will
receive 11.5 million from the EUs 6th Research
Framework Programme and will run until at least
2011.
Fig. 1 Map of Academic and SME partners
participating in GRACE
AIM
The overall aim of GRACE is to combat
antimicrobial resistance through integrating and
strengthening centres of excellence for studying
the application of genomics with primary care
practitioners, to community-acquired LRTI, which
is the leading reason for seeking medical care
and consuming antibiotics. GRACE will develop
into a European LRTI Research Centre to
investigate and improve the point-of-care
management of community-acquired LRTI.
CONCLUSION
LONG TERM IMPACT
GRACE will serve as model of how different but
relevant disciplines in health care can be
integrated and combined and of how the full cycle
of translating basic science innovation into
clinical care can be achieved efficiently and
seamlessly. GRACE will develop into a European
LRTI Research Centre to investigate and improve
the point-of-care management of community-
acquired LRTI.

• Establish the principle and practice of linking
  basic science with clinical care for
  community-acquired LRTI
• Enhance the competitiveness of European
  translational research
• Link science with education and provide a focus
  for spreading of excellent practice throughout
  Europe
• Cement future international research
  collaborations linking international experts in
  primary and secondary care research in
  community-acquired LRTI
• Contribute to EC policy developments
• Strengthen European excellence and achieve a
  leadership on community-acquired LRTI

Fig. 2 Map of primary care networks
participating in GRACE
This project is supported through Priority 1
(Life Sciences, Genomics and Biotechnology for
Health) of European Union's FP6, Contract number
LSHM-CT-2005-518226