Primary Clostridioides difficile infection (pCDI) is a gastrointestinal infection that presents with diarrhea, fever and abdominal pain and is often resistant to antibiotic therapy. pCDI is often a consequence of previous exposure to antibiotics that disrupt the balance of healthy microbes that reside in our gut.
Fecal microbiota transplantation (FMT), the introduction of a healthy microbial community from a healthy donor, has been shown to be safe and highly effective in patients who experience recurrence of CDI, but was not vigorously tested in primary infection. FMT can also fight other deleterious microbes that might reside in the gut. Since FMT contains live bacteria, it needs to be kept frozen until administration.
We have developed a dry compound that does not need freezing (Lyo-FMT) and aim to assess its efficacy for pCDI. This easy-to-administer product will restore the healthy bacterial community, fight infection and reduce the use of antibiotics. If effective, this study will revolutionize the treatment of this worldwide distributed infection.
Project partners
Milena Pitashny, Rambam Health Care Campus, Israel (Coordinator)
Antibiotics are routinely used in both human and animal medicine to treat many serious bacterial diseases. Their use in animals is highly regulated, and ensures better health and welfare of animals. Unfortunately, use of antibiotics over many decades has led to bacteria becoming resistant to these treatments, with antimicrobial resistance being one of the biggest future health risks for humanity.
The European Medicines Agency advocates the use of specific antibiotics for veterinary medicine. These are drugs which are classed as not critically important for human health. Unfortunately, since these drugs were often registered decades ago, with less requirements in terms of dose selection, it is highly probable that the dosage regimens fail to achieve optimal efficacy.
Our team are cross-European specialists in veterinary clinical microbiology and pharmacology and our project is focused on optimizing dosing levels; i.e. using the correct dose at the correct time, for the correct duration, of two drugs in combination: trimethoprim and sulfonamides in seven different animal species. The use of these drugs in an optimal way will both increase the likelihood of successful treatment in animals and reduce the risk of developing further antimicrobial resistance.
This project will lead to better future usage of these drugs in veterinary medicine. The use of accurate treatments will also result in lower reliance on other antibiotics which may be vital for use in human medicine.
Project partners
Aude Ferran, INRAE, French National Institute for Agriculture, Food and Environment, France (Coordinator)
Gudrun Overesch, UNIBE, University of Bern, Switzerland
Ludovic Pelligand, RVC, Royal Veterinary College, United Kingdom
Alexis Viel, ANSES French Agency for Food, Environmental and Occupational Health & Safety, France
Carl Ekstrand, SLU, Swedish University of Agricultural Sciences, Sweden
Mathias Devreese, UG, Ghent University, Faculty of Veterinary Medicine, Belgium
The multidrug-resistant bacteria Klebsiella pneumoniae represents a critically emerging pathogen that confounds treatment in a clinical setting. This is due to their pan-resistance to antibiotics and specific biological traits, including a protective capsule, that makes it insensitive to the host immune system.
Bacterial viruses, also called (bacterio)phages are natural predators of bacteria. Our previous research has identified phages that overcome the capsule barrier by specific enzymes and resensitize bacteria to the innate immune system as well as to antibiotic treatment.
In this project, we introduce the concept of “K-sensitization” which uses these phages and their enzymes (capsule depolymerases) to strip the protective capsules from prevalent K. pneumoniae strains and provide a proof-of-concept of how phages/depolymerases act synergistically to antibiotic treatment. Besides the development of a protocol for compassionate phage therapy against these encapsulated pathogens, we will comprehensively analyze the prevalent K. pneumoniae circulating in human & animal reservoirs, as well as environmental ecosystems. This in turn will lead to the establishment of tailored phage banks & associated diagnostics tools, supported by computational models to ensure rationally designed phage therapy cocktails for antibiotic/phage/enzyme combination treatments. In this manner, the KLEOPATRA consortium aims to contribute to improving the treatment of this critical WHO priority 1 pathogen within a ‘One Health’ setting.
Project partners
Zuzanna Drulis-Kawa, University of Wroclaw, Poland (Coordinator)
Rob Lavigne, KU Leuven, Belgium
Regis Tournebize, Sorbonne Université, France
Joachim J. Bugert, Bundeswehr Institute of Microbiology, Germany
Jens Andre Hammerl, German Federal Institute For Risk Assessment, Germany
Ronen Hazan, Hebrew University of Jerusalem, Israel
JPIAMR is launching an international call for projects under the umbrella of the JPIAMR and within the framework of the ERA-NET JPIAMR-ACTION. The call Disrupting drug resistance using innovative design involves 27 funding organisations from 18 countries. The total estimated call budget is close to 19 million Euro.
This call is closed.
In line with the JPIAMR Strategic Research and Innovation Agenda, this call will focus on tackling the rising threat of antimicrobial resistance. Declining effectiveness of existing antimicrobials together with the low and insufficient number of promising new antimicrobials in the pipeline stresses the urgency to develop new protocols and innovative approaches for effective delivery and use of the already existing antimicrobials. This call aims to improve the treatment of bacterial and fungal infections (including co-infection) and/or the prevention of the emergence/spread of resistance in humans, animals or plants through the improvement of the efficacy, specificity, delivery, combinations and/or repurposing of drugs and plant protection agents.
Through this call, the ERA-NET JPIAMR-ACTION intends to create and reinforce the collaboration between research partners coming from different countries and different fields of expertise to promote research on antimicrobial resistance.
Topic of the call
Proposals should focus on licenced antimicrobial agents (antibiotics/antifungals) or agents under pre-clinical and/or early clinical development, and should address at least one of the following topics:
Improvement of drug/plant protection agent efficacy and/or specificity through chemical modifications (including hit to lead optimisation)
Drug/plant protection agent repurposing;
Optimisation of drug/plant protection agent combinations, alone or with adjunct therapies (including therapeutic vaccines);
Design and implementation of new strategies (including optimisation of drug doses) for improved application, efficacy and delivery of single or combinations of antimicrobials;
Design and implementation of innovative tools, including novel chemistry and/or new materials for improved application, efficacy and delivery of antimicrobials.
Proposals can focus on one or more of the three “One-Health” settings, namely:
Human Health, and/or
Animal Health (including wildlife, livestock, fishes, and companion animals), and/or
Plants (including trees and crops)
The following sub-topics are out of scope of the call:
Antiviral and antiparasitic agents
Discovery and/or screening of new compounds, new vaccines and/or new targets
Proposals solely aiming to develop new diagnostics or new companion diagnostics (companion diagnostics in evaluation of the antimicrobials can be examined but they should not be the main topic of the proposal.)
Participation of end-users, stakeholders and companies is encouraged.
Eligibility
Consortia should consists of a maximum of six (6) project partners (including non-funded partners). The maximum number of partners can be increased to seven (7) if the consortium includes a company, or a partner coming from low or middle income countries, Lithuania or Poland. The budget of non-funded partners shall not exceed 30% of the total transnational project budget requested. Furthermore, consortia should always consist of a majority of project partners eligible for funding. Funding is granted for a maximum of three (3) years in accordance with national regulations and applicable legal provisions.
Timeline
The call Disrupting drug resistance using innovative design will follow a two-step evaluation procedure.
Call text (pdf 1 MB)Updated 2022-01-28: Changes in Annex B (National Rules and Requirements) for the United Kingdom. All specific information on the call “Disrupting drug resistance using innovative design”.
Pre-proposal application form (Word file 0,1 MB). Updated 2022-02-10: Modifications of the table in section B3 and the letter of intent in Annex C. The application form must be attached to the application in the submission platform.
Submission platform. The pre-proposal must be submitted by the coordinator before 8 March 2022, 14h CET using the electronic submission platform.
Applicants from LMIC countries (for more details see Call text, Annex B: National Rules and Requirements):
A live webinar for applicants was held on the 25th of January 2022 presenting the call and the partner search tool. Representatives from funders participating in the call were available to answer questions.
The webinar was recorded and the videos are now available on the JPIAMR YouTube channel:
Partners working in eligible low and middle income countries can be funded by the Swedish International Development Cooperation Agency (Sida).
Belgium Fonds voor Wetenschappelijk onderzoek-Vlaanderen (FWO) Fonds de la Recherche Scientifique (FNRS)
Canada Canadian Institute of Health Research (CIHR)
Czech Republic Ministry of Education, Youth and Sports (MEYS)
Denmark Innovation Fund Denmark (IFD)
Estonia Estonian Research Council (ETAg)
France Agence Nationale de la Recherche (ANR)
Germany The Federal Ministry of Education and Research (BMBF)
Hungary National Research, Development and Innovation Office (NKFIH)
Israel Ministry of Health (CSO-MOH)
Italy Fondazione Regionale per la Ricerca Biomedica (FRRB) Ministero della Salute (It-MoH)
Latvia Valsts Izglitibas Attistibas Agentura (VIAA) Latvijas Zinatnes padome (LZP)
Lithuania Research Council of Lithuania (RCL)
Moldova Agentia Nationala Pentru Cercetare Si Dezvoltare (ANCD)
Poland Narodowe Centrum Nauki (NCN) National Centre for Research and Development (NCBR)
Spain Agencia Estatal de Investgacion (AEI) Instituto de Salud Carlos III (ISCIII)
Sweden Swedish Research Council (SRC) Swedish International Development Cooperation Agency (Sida) Vinnova, Sweden’s innovation agency
Switzerland Swiss National Science Foundation (SNSF)
United Kingdom Medical Research Council (MRC) Biotechnology and Biological Sciences Research Council (BBSRC) Engineering and Physical Sciences Research Council (EPSRC)
Supported projects
Thirteen projects involving 72 partners from 15 different countries have been recommended for funding within the JPIAMR 14th transnational call: “Disrupting drug Resistance Using Innovative Design” The total funding amount is 15,4 M€. Click on the project titles in the list below to learn more on each project.
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