Antibiotic research priorities: ready, set, now go
When faced with a medical emergency and limited resources, triage is essential. Deciding where needs are greatest helps to focus attention and provoke action, in line with a utilitarian aim of maximising gains and minimising harms for the greatest number of people. The importance of setting priorities applies equally to a global emergency as to a local one. With the threat of antimicrobial resistance now recognised at the highest political levels, WHO has compiled a list of pathogens on which research and development of new antimicrobials should be focused.
According to WHO, the top priorities for new drugs are multidrug-resistant Acinetobacter baumannii Pseudomonas aeruginosa, and Enterobacteriaceae, which have been deemed critical threats. Further down the list, common infections such as drug-resistant Neisseria gonorrhoeae, salmonella, Staphylococcus aureus, and campylobacter are included. All-in-all, 12 bacteria are identified, on the basis of mortality, difficulty to treat, ease of transmission, availability of prevention (eg, through good hygiene or vaccination), and whether new drugs are already in development. Knowing one's enemy is the first step to beating it, and the list brings much-needed attention to these infections. But setting priorities has some pitfalls, which WHO, and the wider health community, should try to avoid.
For one, there is the danger of getting your priorities wrong. The evidence base that WHO used to compile and stratify the list is yet to be made public, and so is unavailable for close scrutiny. Although few would disagree that new drugs are needed for the pathogens on the list, inclusion entails exclusion and the omission of multidrug-resistant tuberculosis (MDR-TB) is glaring. Tuberculosis was excluded, as WHO was careful to point out, because other programmes are already dedicated to drug development for MDR-TB. But saying that MDR-TB is a major concern while leaving it off this list risks muddling and diluting the point (the TB Alliance called it “irresponsible”). How important is MDR-TB compared with multidrug-resistant Enterobacteriaceae? Are unique incentives needed for MDR-TB drug development, or not? The simplest messages are usually the most effective, and WHO risks weakening any sense of urgency with the omission. Drug-resistance in tuberculosis is much more than a potential cause of disease in the near future: it is an ongoing independent health crisis with half a million cases worldwide, and as such it should be at the front and centre of any global endeavour to develop new antibiotics.
The absence of MDR-TB might catch the eye, but other exclusions should also be noted. Clostridium difficile causes a huge burden of disease and new narrow-spectrum drugs are needed. If antibiotic development for C difficile was slow before, it could stall entirely if antimicrobial research and development focuses entirely on the pathogens on WHO's list. Vigilence is needed to ensure that incentives for drug development are applicable beyond the bounds of the priority pathogens.
It is insufficient to set priorities alone—they need to be acted on. The list was generated with an eye to the G20 meeting taking place in Germany in July, at which antimicrobial resistance will feature on the agenda. Hermann Gröhe, the German Minister of Health, greeted the publication of the list, saying that “we will discuss and bring the attention of the G20 to the fight against antimicrobial resistance”. But discussion and attention are not enough. Projects such as the Medicines for Malaria Venture and the Drugs for Neglected Diseases Initiative could provide the template for stimulating drug development in neglected areas of infectious diseases. With the US 21st Century Cures Act helping to smooth the regulatory process for new antimicrobials, we look forward to seeing what actions the G20 will take to aid discovery.
The list of priorities for research is an essential and welcome step in addressing antimicrobial resistance. But it is the easiest element. Indeed, there is nothing novel about suggesting that new antimicrobials are needed for drug-resistant Gram-negative infections. What comes next—discovering and developing new antimicrobials for these diseases—will be the difficult part. The top priority now for antimicrobial research and development is not A baumannii S aureus, or MDR-TB. It is to find a way to bring together pharmaceutical companies, governments, civic society, and academics to overcome decades of stagnation, to stimulate research, and to generate some effective new medicines.
For more on the WHO list of priority pathogens see http://www.who.int/medicines/publications/global-priority-list-antibiotic-resistant-bacteria/en/
Source: The Lancet Infectious Diseases
