WHO priority pathogen list for R&D published

The WHO priority pathogen list for R&D was recently published. I contributed my R&D expertise to this intense work. The list should prioritise and guide R&D of new antibiotics, as part of WHO’s efforts to address growing global resistance to antimicrobial drugs. The process was based on collecting all available evidence to develop criteria that were used in a multi-criteria decision analysis technique vetted by a group of international experts.

The list is an important step to spur governments to put in place policies that incentivize basic science and R&D by both publicly funded agencies and the private sector investing in new antibiotic discovery.

List

DRIVE-AB Conference in Amsterdam

The DRIVE-AB Conference Stimulating innovation, sustainable use and global access to antibiotics will take place on 2 and 3 June 2016 in Amsterdam. This conference, generously funded by the Government of the Netherlands and organized by the IMI DRIVE AB consortium, will bring together about 150 invited decision-makers and policy influencers from around the world to explore current and proposed efforts to address antibiotic resistance. The main goal of the meeting is to move beyond discussions and instead identify key policies that can be implemented globally to both stimulate the innovation of critically-needed new treatments and ensure their availability and responsible use. Input from the conference will help inform DRIVE AB’s policy recommendations to the European Commission—an important part of growing global discussion on how to manage the looming public health threat of resistance.

G7 Health Ministers address antibacterial resistance

The G7 Health Ministers discussed antibacterial resistance during the G7-Meeting in Berlin on 8 and 9 October 2015.

The “Berlin Declaration on AMR” includes strong committments to:

• Improve the coordination between global initiatives and  joint international efforts encompassing human and animal health, agriculture and the environment.
• National AMR Action Plans will take into account the requirements of the WHO Global Action Plan.
• Support other countries with the development and implementation of their National Action Plans, building global capacity to combat AMR and coordinating activity.
• Three-fold approach to AMR: improving infection prevention and control; conserving the effectiveness of existing and future antimicrobials; engaging in research to optimise such approaches and to develop new antimicrobials, vaccines, treatment alternatives and rapid diagnostic tools.
• Pool the national efforts in order to share best practices and promote the prudent use of antimicrobials among all relevant stakeholders.
• Increase awareness among the general public of the impact of AMR .
• Call on all countries to enforce the availability of antibiotics by prescription only.
• Strengthen antibiotic stewardship programs for professionals.
• Ensure the production of high quality antimicrobials in human and veterinary medicine.
• Strengthen surveillance systems on AMR and antimicrobial consumption.
• Inform research prioritization and encourage the research and development of new antimicrobials, vaccines, alternative treatment options and diagnostics.
• Explore innovative economic incentives to enhance the research and development of new antibiotics, other therapeutic options, and diagnostics, e.g. a global antibiotic research fund and a market entry reward mechanism for truly new antibiotics targeting the most important pathogens and most needed for global public health.
• Explore the feasibility and need of setting up a global antibiotic product development partnership.
• Encourage international cooperation on antimicrobial stewardship and regulatory dialogue on the approval and regulation for antibiotics.

DRIVE-AB supports this initiative and will provide scientific data to inform the decisions regarding antibiotic stewardship (metrics to define the prudent antibiotic use) and innovative economic incentives to encourage research and development of new antibiotics.

Global antibacterial resistance: The never-ending story

New resistance mechanisms evolve, resistant bacteria are spreading quickly in some parts of the world. The topic of resistance finds increasingly interest as physicians are confronted with infections caused by multi-drug resistant, extensively- drug resistant and even pan-drug resistant bacteria without any therapeutic option.

The new Journal of Global Antimicrobial Resistance focuses on the global spread of antibiotic-resistant microbes. It has received its first Impact Factor despite not being indexed yet by PubMed. My paper, published 2 years ago, is the most-cited paper from this new journal: Global antibacterial resistance: The never-ending story.

Re-development of old antibiotics

In the face of increasing antimicrobial resistance and the paucity of new antimicrobial agents it has become clear that new antimicrobial strategies are urgently needed. One of these is to revisit old antibiotics to ensure that they are used correctly and to their full potential, as well as to determine whether one or several of them can help alleviate the pressure on more recent agents. Strategies are urgently needed to ‘re-develop’ these drugs using modern standards, integrating new knowledge into regulatory frameworks and communicating the knowledge from the research bench to the bedside. Without a systematic approach to re-developing these old drugs and rigorously testing them according to today’s standards, there is a significant risk of doing harm to patients and further increasing multidrug resistance.

The recently published paper REVIVING OLD ANTIBIOTICS describes factors to be considered and outlines steps and actions needed to re-develop old antibiotics so that they can be used effectively for the treatment of infections.

Theuretzbacher U, Van Bambeke F, Cantón R, Giske CG, Mouton JW, Nation RL, Paul M, Turnidge JD, Kahlmeter G: Reviving old antibiotics. J Antimicrob Chemother. 2015 Jun 10. pii: dkv157

G7 summit June 2015

The leaders of the G7 agreed on concrete steps with regard to antimicrobial drug resistsance to respond to some of the most pressing issues in the world:

“Antimicrobials play a crucial role for the current and future success of human and veterinary medicine. We fully support the recently adopted WHO Global Action Plan on Antimicrobial Resistance. We will develop or review and effectively implement our national action plans and support other countries as they develop their own national action plans.

We are strongly committed to the One Health approach, encompassing all areas — human, and animal health as well as agriculture and the environment. We will foster the prudent use of antibiotics and will engage in stimulating basic research, research on epidemiology, infection prevention and control, and the development of new antibiotics, alternative therapies, vaccines and rapid point-of-care diagnostics. We commit to taking into account the annex (Joint Efforts to Combat Antimicrobial Resistance) as we develop or review and share our national action plans.”

Let’s hope that real action will follow the nice words.

Obama on antibacterial resistance

Though Ebola is dominating the news other health threats such as antibiotic resistance have not disappeared.

In September, President Barack Obama signed an executive order to establish a new task force dedicated to addressing antibiotic resistance.

The national strategy lays out a series of steps to address the decreasing effectiveness of antibiotics; many are similar to those identified in April by the World Health Organization. They include establishing surveillance systems for tracking the spread of antibiotic-resistant infections in health-care and agricultural settings, providing financial and regulatory incentives for researchers and pharmaceutical companies to develop new antibiotics and devising methods to quickly diagnose antibiotic-resistant infections.

The White House action comes at the same time as the release of the report on antibiotic resistance from the President’s Council of Advisors on Science and Technology (PCAST).

More on the European strategy next week!

Global antibacterial resistance: The never-ending story

My recent publication Global antibacterial resistance: The never-ending story features the threat of multidrug-resistant pathogens that are spreading globally with unprecedented speed. According to their resistance epidemiology (based on major drivers favouring resistance), I highlighted three regions as high-impact resistance hot spots. In a globalised world, we all may be affected by potentially untreatable infectious diseases in the future.

Due to limited therapeutic options for the management of these difficult-to-treat pathogens an international panel of experts from Europe, the Americas and Asia discussed the issues of management of  infections caused by multidrug-resistant and extensively drug-resistant Gram-negative bacilli in a consensus conference as part of the 13th Asia-Pacific Congress of Clinical Microbiology and Infection. I organized the publication of the conference results based on the achieved consensus of the experts. Though important clinical evidence is scarce this publication will hopefully contribute to an improved management of these patients.

Publicly funded antibacterial drug development in Europe

The urgent need for new antibacterial drugs to treat multidrug-resistant Gram-negative infections is well recognized as a public health emergency. Discovery and development of new drugs is hampered by a number of scientific and clinical development hurdles that cannot be tackled by any individual organisation working alone.  To reinvigorate research into new antibiotics the European public-private partnership Innovative Medicines Initiative (IMI) has launched the first two projects of its programme ‘New Drugs for Bad Bugs’ (ND4BB). The new projects, COMBACTE (Combatting Bacterial Resistance in Europe) and TRANSLOCATION (Molecular basis of the bacterial cell wall permeability), will focus on new models for the clinical development of antibiotics as well as address new ways of getting antibiotics into Gram-negative bacteria and preventing efflux of the drugs. An important topic of the current call is the discovery and development of new drugs combatting Gram-negative infections (Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and E. coli) from the discovery of hits to leads and Development Candidates to Phase 1 clinical studies. The planned EU budget for the current call is 59M €. The goal of this call is to deliver 1-2 novel mode of action Gram-negative antibacterial ready for Phase 1 clinical trials within 5-6 years.

At the same time, the European Commission is planning the details of the next funding frame work Horizon 2020. Special aspects of antibacterial drug R&D included in the next funding period will be discussed at the Superbugs & Superdrugs Conference in London, 4^th and 5^th March 2013. I will present the topic “Publicly funded antibacterial drug development in Europe” and will be a panel member of the Round Table Discussion including Richard Bax (TranScrip Partners), Richard Bergstrom (Director General, European Federation of Pharmaceutical Industries and Associations, EFPIA), Ursula Theuretzbacher (Center For Anti-Infective Agents), Line Matthiessen, Head of Infectious Diseases and Public Health Unit, European Commission). We hope for a lively discussion that will address key aspects of antibacterial drug development from the point of view of all involved stake holders. All these discussions and contributions of stake holders will be considered when finalizing the calls of the next funding round.

The World Economic Forum

The Global Risks Report 2013 has just been published and analyses 50 global risks in terms of impact, likelihood and interconnections. To summarize:  The world is not safer and global risks become more worrying.

This year’s findings include the chapter “The dangers of hubris to human health” that describes how antibiotic resistance can overwhelm not only our health systems but also damaged our social and economic systems. I would recommend reading this report as a good source for reflecting the contribution of each of us to the increasing global risks. Taking antibiotics when they are not helpful and necessary is a small step to a future world with multidrug resistance and a lack of effective antibiotics.

Here is the report: http://www3.weforum.org/docs/WEF_GlobalRisks_Report_2013.pdf