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 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. 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. AIM LONG TERM IMPACT 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 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. CONCLUSION POTENTIAL APPLICATIONS 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 Fig. 1: Map of Academic and SME partners participating in GRACE Fig. 2: Map of primary care networks participating in GRACE 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 EU’s 6th Research Framework Programme and will run until at least 2011. Behaviour and expectations of doctors and patients? Aetiology? Diagnostic strategies? Prediction of poor outcome? Treatment? Cost-effectiveness? Potential of genetics to enhance clinical care? GAPS IN KNOWLEDGE ON CA-LRTI