The entire structure of health-care delivery for effective antibiotics - from research and development, to distribution and rational use - needs to be re-engineered to address the looming global threat of antibiotic resistance, say the authors of a new report, published in The Lancet Infectious Diseases, ahead of European Antibiotic Awareness Day, and the US Centers for Disease Control and Prevention (CDC) 'Get Smart About Antibiotics Week' on Monday 18 November.
The report, which was compiled by an international group of 26 leading experts in the field, presents a comprehensive global overview of the growing problem of antibiotic resistance, its major causes and consequences, and identifies key areas in which action is urgently needed.
Antibiotic resistance arises when bacteria evolve mechanisms to withstand the drugs which are used to fight infection. Recent decades have seen vast increases in the use of antibiotics across medicine and agriculture, and in the absence of adequate regulatory controls, treatment guidelines, and patient awareness, this has led to a huge global surge in antibiotic resistance. The problem is compounded by a desperate shortage of new drugs to treat multi-drug resistant bacterial infections.
According to lead author Professor Otto Cars, of Uppsala University in Sweden and ReAct Action on Antibiotic Resistance, "The causes of antibiotic resistance are complex and include human behaviour at many levels of society; the consequences affect everybody in the world. Within just a few years, we might be faced with unimaginable setbacks, medically, socially, and economically, unless real and unprecedented global coordinated actions to improve surveillance and transform the way antibiotics are regulated and developed are taken immediately."*
Despite growing awareness of the problem of antibiotic resistance, reinforced by recent high-profile announcements and reports from the World Health Organisation, the UK's Chief Medical Officer, and the US CDC, the report authors point out that action needs to be coordinated both nationally and internationally, and this coordination is still largely absent, especially at the political level.
"Only now has the awareness and urgency of the problem of antibiotic resistance reached a level that a new sustainable global system to counteract these problems can be built," says Professor Cars. "Addressing these problems will require nothing less than a fundamental shift in how antibiotics are developed, financed, and prescribed."*
According to the authors, the paucity of new antibiotic drugs in recent decades has arisen from a combination of significant scientific challenges, low financial returns compared with many other medicines such as those for chronic diseases, and the regulatory environment.
Rebuilding the infrastructure of academia and industry to face the threat of antibiotic resistance will not only require national and international political commitment and investment, but also new ways of financing drug development. Investment in new drugs is usually based on expectations of large volume sales. In the case of antibiotics, this can lead to aggressive marketing and sales activity, which in turn results in over-prescription, especially when in many countries, financial incentives for doctors and health-care systems mean that over-prescription of antibiotics makes sound financial sense.
Addressing these problems will require innovative and sustainable financing models which delink research and development investment from revenue returns. Taking a systems approach, solutions will need to realign incentives and build in effective feedback loops. The authors also suggest that academic research institutes and small and medium sized enterprises (SME), across the world, need to play a greatly increased part in antibiotic discovery to address the currently inadequate infrastructure and innovative capacity.
All of this needs to be done in a way that balances curtailing excess antibiotic use with ensuring access to the people who most need them, especially children in the poorest regions of the world. Rapid point-of-care diagnostic tests providing information on the pathogen and its susceptibility to antibiotics have enormous potential to minimize inappropriate antibiotic use and to increase patient safety.
Non-therapeutic use of antibiotics in animals similarly must be curbed. Non-prescription sales of antibiotics must be banned wherever possible to reduce the massive global overuse, but this has the potential to cut off access to antibiotics for some of the world's poorest and most marginalised people, many of whom do not have access to clean water and hygiene and are at an increased risk of acquiring infections. Addressing this problem will require solutions that are sensitive to local resources and cultural beliefs as well as empower and engage inclusively consumers and providers alike, say the authors.
"Antibiotic resistance is a complex ecological problem which doesn't just affect people, but is also intimately connected with agriculture and the environment," says Professor Cars. "We need to move on from 'blaming and shaming' among the many stakeholders who have all contributed to the problem, towards concrete political action and commitment to address this threat. Consumers and providers of antibiotics alike need to be empowered to tackle antibiotic resistance, as well as ensuring that those in need benefit from affordable, effective antibiotics."*