2.3.1 Anti-microbial drug resistance

The strategic objective of this area is to confront the increasing emergence and spread of antimicrobial drug resistant pathogens in Europe and in a multi-disciplinary approach through the development of effective infection prevention and control strategies. Clinical trials of offpatent antibiotics will take into account not only clinical outcome, but also impact on resistance development. Focus on microbial ecology will allow for a better understanding of the dynamics and evolution of resistance traits and thereby reveal for new intervention opportunities. A multi-disciplinary integrated effort will be made to address the public health threat posed by Gram negative multi-drug resistant bacteria. SMEs will be mobilized to develop new technologies for diagnostic tests and for controlling biofilm formation in the clinical environment.

Note: Depending on the topics listed below, applicants should follow the rules for single or two-stage submission procedure (see also respective call fiche in section III).

HEALTH.2011.2.3.1-1 Investigator-driven clinical trials (1) of off-patent antibiotics. FP7- HEALTH-2011-two-stage.

Research should aim at defining optimal treatment regimens (including drug choice, combinations, dosing, duration of therapy, PK/PD, individualisation) of off-patent antimicrobial agents for therapy of difficult-to-treat infections caused by multidrug resistant bacterial pathogens in order to maximise clinical benefit and minimise selection for resistance. Research-intensive SME participation is highly encouraged and this will be considered in the evaluation of the proposal. In this work programme several topics for investigator-driven, multicentre, prospective, controlled clinical trials are called for. The outcomes must be relevant for patients and change clinical practice. Pilot studies and systematic reviews will not be funded. Applicants must demonstrate that clinical trials are appropriately powered to produce statistically significant evidence. Gender aspects and differences related to age subgroups should be appropriately considered. The clinical trials to be supported must be registered in a publicly accessible clinical trials registry. The applications must consider the relevant governance issues for clinical trials such as good clinical practice and respect of the appropriate international, European and national legislation and guidelines.

Note: Limits on the EU financial contribution apply. These are implemented strictly as formal eligibility criteria.
Funding scheme: Collaborative Project (small or medium-scale focused research project).
Requested EU contribution per project: Maximum EUR 6 000 000.
One or more proposals can be selected.
Expected impact: These types of studies should allow for the identification of optimal treatment regimens by off-patent antibiotics of infections caused by multi-drug resistant bacterial pathogens, as well as an improved standardisation of such treatments. Not only clinical outcome, but also impact on drug resistance should be taken into account. Where relevant, patient advocacy groups, which can contribute to the quality, feasibility and impact of clinical trials should be involved. The degree of such participation will be considered during the evaluation..

HEALTH.2011.2.3.1-2: Multi-disciplinary research on the evolution and transfer of antibiotic resistance. FP7-HEALTH-2011-single-stage.

Research should aim to study the human microbiome with its vast number of bacterial species that forms a reservoir in which antibiotic resistance emerges in human pathogens. The resistance genes that are present in the human microbiome need to be characterized, and their potential to transfer to other pathogenic or non-pathogenic bacteria needs to be investigated. The dynamics and evolution of the interaction between the resistant and non-resistant human microbiome over time needs to be addressed using for instance metagenomics or other state-of-the-art techniques. Research should also aim to elucidate interactions of the human microbiome with environmental, animal and food reservoirs. The characterization of the resistance reservoirs should provide deeper knowledge on the evolution and transfer of resistance and establish methods that allow for the prediction of the flow of genes and organisms between different environments and future resistance trends.

Note: Limits on the EU financial contribution apply. These are implemented strictly as formal eligibility criteria.
Funding scheme: Collaborative Project (large-scale integrating project).
Requested EU contribution per project: Maximum EUR 12 000 000.
Only up to one proposal can be selected.
Expected impact: This multidisciplinary research is likely to elucidate the relationship between different reservoirs of resistant pathogenic bacteria and thereby open up avenues for novel intervention approaches. A strong participation of SMEs in the project should help ensuring innovation in this area/topic. The degree of active participation of research-intensive SMEs will be considered during the evaluation.

HEALTH.2011.2.3.1-3 Management of Gram negative multi-drug resistant infections. FP7-HEALTH-2011-single-stage.

Research should focus on innovative methods aimed at a better control of Gram negative multi-drug resistant infections both in health-care settings as well as in the community. Hospital- and community-based intervention studies will be performed; the link to carriage and colonization, dynamics of transmission, and the clinical impact of measures to decrease the burden of resistant strains will be addressed. Research will include evaluation of rapid tests for reliable detection of Gram negative multi-drug resistant infections, including clonal identification and resistance in order to direct empiric therapy and infection control measures. Observational studies should be carried out to understand the role of gastro-intestinal carriage in causing infection and in resistance gene transfer among Gram negative organisms. Research will also include evaluation of population-based interventions to control the spread of Gram negative multi-drug resistant organisms in the community and hospital settings, including new decolonization approaches, test of efficacy of different decolonization regimens in clinical trials, ecology and evolution of resistance in the gastrointestinal tract including measures to preserve the gut flora and prevent the spread of resistance. Research will also determine optimal treatment regimens for common infectious disease conditions (e.g. urinary tract infection, hospital-acquired infections). Mathematical models of the within-host interaction between the multi-resistant and non-resistant Gram negative bacterial microbiome and their dynamics and evolution will be established, as well as models allowing the prediction of future spread using different macro-epidemiologic scenarios.

Note: Limits on the EU financial contribution apply. These are implemented strictly as formal eligibility criteria.
Funding scheme: Collaborative Project (large-scale integrating project).
Requested EU contribution per project: Maximum EUR 12 000 000.
Only up to one proposal can be selected.
Expected impact: This research should improve the management of Gram negative multidrug resistant infections in the community as well as in health-care settings. Research aimed at a better understanding of the transmission and detection will benefit patients by decreasing infection rates and/or improving recovery. Furthermore, improved management of Gram negative infections is expected to retard the development of multi-drug resistance. A strong participation of SMEs in the project should help ensuring innovation in this area/topic. The degree of active participation of research-intensive SMEs will be considered during the evaluation.

HEALTH.2011.2.3.1-4 Development of multi-analyte diagnostic tests. FP7-HEALTH- 2011-two-stage.

Research should aim to develop novel diagnostic tools. Managing the problem of bacterial resistance relies on the rapid identification of resistant pathogens in a clinical setting. The vast numbers of pathogenic bacteria that can contain a variety of resistance mechanisms underline the need for multi-analyte diagnostic tests that are fast and reliable. Tests should aim to distinguish bacteria from viruses, should detect markers for severity of infection and identify resistance/susceptibility patterns. The availability of robust diagnostic tests is required to allow an evidence-based system of antibiotic resistance management. The development of such diagnostic tools and their introduction in clinical settings should be aimed for, with the ultimate goal to tailor antibiotic prescription to the individual patient.

Note: Limits on the EU financial contribution apply. These are implemented strictly as formal eligibility criteria.
Funding scheme: SME-targeted Collaborative Project.
Requested EU contribution per project: Maximum. EUR 3 000 000.
One or more proposals can be selected.
Expected impact: The availability of multi-analyte diagnostic tests is expected to allow for antibiotic prescription that takes both the type of infection of the patient, and the presence of resistant pathogens in the clinical setting into account. Such improved prescription should speed up patient recovery and retard the development of multi-drug resistance.
Specific feature: SME-targeted research is designed to encourage SME efforts towards research and innovation. Priority will be given to proposals demonstrating that research intensive SMEs play a leading role. The projects will be led by SMEs with R&D capacities, but the coordinator does not need to be an SME. The expected project results should clearly be of interest and potential benefit to SME(s).
Additional eligibility criterion: SME-targeted Collaborative Projects will only be selected for funding on the condition that the estimated EU contribution going to SME(s) is 30-50% or more of the total estimated EU contribution for the project as a whole. This will be assessed at the end of the negotiation, before signature of the grant agreement. Proposals not fulfilling this criterion will not be funded.

HEALTH.2011.2.3.1-5 Development of tools to control microbial biofilms with relevance to clinical drug resistance. FP7-HEALTH-2011-two-stage.

Research should aim at the development of tools to control biofilms . The formation of biofilms of pathogenic bacteria and fungi affects sensitivity and resistance to antibacterial and antifungal drugs and therefore represents a clinical problem. Novel tools that allow the disruption of biofilms and decrease infection rates would be useful. Such tools aimed at controlling biofilms should allow the development of strategies aimed at improving patient management.

Note: Limits on the EU financial contribution apply. These are implemented strictly as formal eligibility criteria.
Funding scheme: SME-targeted Collaborative Project.
Requested EU contribution per project: Maximum EUR 3 000 000
One or more proposals can be selected Expected impact: The availability of tools to control biofilm formation is expected to allow for a better management of infections caused by pathogenic bacteria and fungi. Tools that disrupt biofilms or prevent their formation will improve the treatment of infections caused by pathogenic bacteria and fungi.
Specific feature: SME-targeted research is designed to encourage SME efforts towards research and innovation. Priority will be given to proposals demonstrating that research intensive SMEs play a leading role. The projects will be led by SMEs with R&D capacities, but the coordinator does not need to be an SME. The expected project results should clearly be of interest and potential benefit to SME(s).
Additional eligibility criterion: SME-targeted Collaborative Projects will only be selected for funding on the condition that the estimated EU contribution going to SME(s) is 30-50% or more of the total estimated EU contribution for the project as a whole. This will be assessed at the end of the negotiation, before signature of the grant agreement. Proposals not fulfilling this criterion will not be funded.

(1) http://ec.europa.eu/enterprise/sectors/pharmaceuticals/documents/eudralex/vol-10/
Please consult also the text for clinical trials provided in the introduction to activity 2. Translating research for human health in this work programme on pages 17/18