Inhibition of antimicrobial drug resistance: Exploiting an old drug as a basis for inhibitory discovery


Research Network: 2017-01-01 - 2017-12-31
Total sum awarded: €40 045

Antimicrobial resistance (AMR) is a serious emerging threat for patients and the healthcare systems. It has been anticipated by the Institute and Faculty of Actuaries in Britain that AMR has the potential to reduce Gross Domestic Product (GDP) by 3.5% globally and to kill an additional 10 million people by 2050, and as such the topic is of high importance to the public. Our working group will highlight the efforts made in the field by academics and industry alike and raise awareness on the urgency of action and proposes the use of an old nitrofuran drug for future development of potent antimicrobials by intense study of its use, potency, and the fundamental science behind its mode of action and resistance mechanisms. The inclusion of distinguished and prominent scientists in the field coming from different backgrounds will emphasize a multidisciplinary effort is needed to tackle the serious problem of AMR in a timely fashion.

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  • Klaas Martinus Pos, Goethe University Frankfurt, Germany (Coordinator)
  • Annie Ducher, DaVolterra, France (Observer)
  • Laura Piddock, University of Birmingham, United Kingdom (Observer)
  • Dan Andersson, Uppsala University, Sweden (Observer)
  • Johan Mouton, Erasmus MC University Medical Center, Netherlands (Observer)
  • Peter Hawkey, University of Birmingham, United Kingdom (Observer)
  • Sara Jabbari, University of Birmingham, United Kingdom (Observer)
  • Francisco Fernandez-Trillo, University of Birmingham, United Kingdom (Observer)
  • Thomas Wichelhaus, Goethe University Frankfurt, Germany (Observer)
  • Eugen Proschak, Goethe University Frankfurt, Germany (Observer)

The alarming increase in the numbers of infections by multidrug-resistant Gram-negative pathogens in the EU calls for new strategies and solutions to address bacterial resistance mechanisms. In response to a call from the Goethe University Frankfurt and the University of Birmingham, UK, researchers from both institutions held a 2-day workshop in March 2016 with the aim of designing new strategies and solutions to drug resistance mechanisms. This workshop identified that there is an unmet need for a new oral agent active against multi-drug resistant Enterobacteriaceae causing urinary tract infections (UTIs) including in the elderly. To further address the question of feasibility of such a research proposal, we proposed a new network group including researchers from the Birmingham workshop plus additional experts with skills in medical microbiology, pharmacokinetics, in vivo models, and drug discovery/development in industry. We organized a two-day event. On the first day, a conference in Frankfurt was held including talks from the WG members and invited experts in the field, discussion and opinion sessions. On day two, a working group meeting was held to distil all aspects of the conference and to formulate a research programme which will be the basis of an application to a H2020 call. This event was followed by a meeting on September 28th, 2017 in Frankfurt. Here the Work Packages were defined for a proposed consortium, as well as identification of potential funding opportunities. Moreover, we selected members of the consortium to contribute to a special issue on nitrofurantoin, focussing on its mechanism of action, resistance, PK/PD, and epidemiology.