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Antibacterial agents in clinical development

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Context - The rise of antibiotic-resistant bacteria is a serious public health issue. The development of new drugs with antibacterial activity is one of the key elements of a strategy to address this threat.

This WHO report highlights the priorities for combatting antimicrobial resistance.

It looks at new treatments that are in phase 1, 2 or 3 clinical trials for which information is publicly available but do not yet have market authorization anywhere in the world for human use.

This is a faithful summary of the leading report produced in 2017 by the World Health Organization (WHO): "Antibacterial agents in clinical development - An analysis of the antibacterial clinical development pipeline, including tuberculosis " 

  • Source document:WHO (2017)
  • Summary & Details: GreenFacts
Latest update: 3 November 2017

How has resistance to antibiotics emerged?

Bacterial resistance is a natural phenomenon. There are infectious agents that are resistant to basic antibiotics, some that can resist multiple antibiotics, and some that are even resistant to all available treatment options. The misuse and overuse of antibiotics unfortunately accelerate the inevitable development of this resistance of bacteria to any antibiotic that is used in treating infections. To fight this, antibiotics should be used more responsibly and new antibacterial treatments should be developed to counteract emerging resistance. There are infectious agents that are resistant to basic antibiotics, some that can resist multiple antibiotics, and some that are even resistant to all available treatment options. Considering that the number of new antibiotics has fallen significantly since the 1980s, this situation requires urgent, coordinated action at global, regional and national levels.

What antibiotic-resistant pathogens are a priority?

Tuberculosis (TB) is the number one global infectious disease killer today, causing 1.8 million deaths per year. Drug-resistant TB is the most common and lethal airborne antimicrobial-resistant disease worldwide today, responsible for 250 000 deaths each year. The problem is that in over 70 years only two new antibiotics for treatment of multi-drug-resistant-TB have reached the market. Research and development investment in TB is at its lowest level since 2008.

The other pathogens of critical priority are those that are resistant to carbapenem, a drug already used for the treatment of resistant infections, which is administered intravenously in hospital settings.

What is the present status of the development of new antibiotics?

More innovative products are required against pathogens but, as there is a lack of potential treatment options for priority resistant bacteria, the current clinical pipeline is still insufficient to mitigate the threat of antimicrobial resistance.. Also, although oral formulations for community diseases associated with high morbidity are essential, too few oral antibiotics for infections caused by Gram-negative pathogens are under development.

What is the present status of the development of new antibiotics?

Almost all the new antimicrobial agents are only modifications of existing antibiotic classes and address specific resistance mechanisms. They are active thus only against specific pathogens or a limited subset of resistant strains.

As of May 2017, 33 antibiotics and 9 biological agents, including monoclonal antibodies and endolysins (a class of enzymes derived from viruses that attack bacteria), that target priority pathogens, were in the clinical pipeline with 7 products against tuberculosis (TB) and 9 against C. difficile infections. Among the 33 antibiotics, 8 belong to five distinct new antibiotic classes and they fulfil at least one of the four criteria that were used to assess the extent to which antibacterial agents can be classified as innovative:

  • absence of cross-resistance to existing antibiotics;
  • new chemical class;
  • new target;
  • new mechanism of action.

Therapeutic options for multidrug-resistant Gram-positive pathogens, specifically methicillin-resistant Staphylococcus aureus, have increased with the marketing approval of new antibiotic classes but new treatments for those pathogens are still required to keep up with the anticipated evolution of resistance.

Another highly important pathogen, vancomycin-resistant Enterococcus spp., has received little attention and the situation is worse for Gram-negative bacterial infections emerging worldwide and that cannot be treated with any of the antibiotics currently on the market.

What else should be done to mitigate the threat of antibiotic resistance?

The development of new antibiotics should go hand in hand with infection prevention and control activities, and fostering of appropriate use of existing and future antibiotics through information and stewardship measures. The WHO Global Development and Stewardship Framework to Combat Antimicrobial Resistance should in particular provide the necessary guidance for using antibiotics more responsibly in the human, animal and agricultural sectors.

In this context the WHO regularly updates its guidelines on appropriate prescribing of antibiotics : How to stop antibiotic resistance? Here's a WHO prescription 1

1 How to stop antibiotic resistance? Here's a WHO prescription.
http://www.who.int/mediacentre/commentaries/stop-antibiotic-resistance/en/ 
Licence: CC BY-NC-SA 3.0 IGO.


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