Tackling antibiotic resistanceBMJ 2010; 340 doi: http://dx.doi.org/10.1136/bmj.c2071 (Published 18 May 2010) Cite this as: BMJ 2010;340:c2071
- Anthony D So, director, Program on Global Health and Technology Access1,
- Neha Gupta, associate in research1,
- Otto Cars, chairman and founding executive director of ReAct (Action on Antibiotic Resistance)2
- 1Terry Sanford School of Public Policy, Duke University, 302 Towerview Drive, Box 90314, Durham, NC 27708, USA
- 2Department of Medical Sciences, Uppsala University, Box 256, 751 05 Uppsala, Sweden
The twin challenge of conserving the effectiveness of existing antibacterial drugs and developing new ones is attracting attention in policy circles. In September 2009, a conference organised under the auspices of the Swedish European Union presidency highlighted the need to provide incentives for developing new antibacterial drugs. In the linked article (doi:10.1136/bmj.c2115), Morel and Mossialos provide an inventory of incentives, prepared for that conference, to promote research and development for new treatment options.1
Last November, the summit between the EU and the United States announced a transatlantic task force on antimicrobial resistance that will tackle “appropriate therapeutic use of antimicrobial drugs in the medical and veterinary communities, prevention of both healthcare- and community-associated drug-resistant infections, and strategies for improving the pipeline of new antimicrobial drugs.”2
In the US, the annual cost of treating resistant nosocomial infections traceable to six bacteria exceeded $1.87bn (£1.2bn; €1.4bn), greater than the yearly cost of treating influenza.3 In the EU, added costs and loss of productivity as a result of antibiotic resistance conservatively amount to €1.5bn.4 This problem is not just transatlantic, but global. Tuberculosis claims 1.8 million lives each year, and typhoid fever takes another 200 000.5 Multidrug resistance has forced clinicians to fall back on second line and third line regimens, which multiplies treatment costs. Especially in developing countries, such cost barriers compound irrational use.
With the announcement of the EU-US task force, the Infectious Diseases Society of America has called for committing to a goal of developing 10 new antibacterial drugs by 2020.6 Catchy as 10×20 sounds, the public sector strategy for funding such research and development must prioritise among different health technologies, such as diagnostics and vaccines, to combat antibiotic resistance. For example, three million children die each year from acute respiratory bacterial infections in developing countries, but penicillin sensitive pneumococcal strains have declined to a half, even a quarter, in some countries. A diagnostic test for bacterial pneumonia would save an estimated 405 000 lives a year, by targeting treatment and avoiding overprescription of antibiotics.7 New vaccines may also reduce reliance on drugs as the use of pneumococcal vaccine has suggested.
The incentives for new antibacterials must not only fuel the sprint to goals like 10×20, but must also sustain the marathon of antibiotic development well into the future. With far more lucrative therapeutic categories in which to invest, large firms may ignore research and development in the field of antibiotics. Making the next new antibiotic a blockbuster though is not the solution. Small firms, which face different opportunity costs, may wish to pursue new antibiotics but not have the capital to do so. Rather than rely on extended patent terms or data exclusivity8—incentives with payoffs too far down the pipeline—the public sector might focus on enabling greater access to low cost capital and to upstream research tools, such as compound libraries of potential new drugs.
To ensure rational use, these products will also have to be affordable in resource-limited settings. Delinking research and development costs from drug pricing and the return that drug companies receive on investment could correct misaligned economic incentives. But this will require innovative financing approaches, from public financing of clinical trials to prizes.9 10 If the public sector wants these drugs to be for the public good, then it must carefully invest in the right package of incentives to achieve both innovation and access.
Better financing is only part of the picture. Beyond incentives, the way that innovations are brought from bench to bedside will need to be re-engineered to meet major scientific challenges. Lessons can be learnt from tuberculosis—for which no new drug has been developed in decades and we still rely on century old diagnostic methods. The Global Alliance for Tuberculosis has sought to produce promising drug candidates, even posting prizes on InnoCentive, and its “critical path to tuberculosis regimens” may shave years off the time needed for regulatory approval of combination treatments. India’s Council of Scientific and Industrial Research has embarked on an Open Source Drug Discovery initiative. Eli Lilly has transferred the production of cycloserine for treating multidrug resistant tuberculosis to generic drug makers to ensure its continued availability. Although some of these initiatives are fledglings, they represent efforts to rethink traditional paradigms of bringing drugs to market.
Today’s dearth in the antibacterial research and development pipeline will take decades to reverse. To complement the strategy to bring new drugs to market, concerted action must be taken now to conserve existing drugs. Strategies to realign economic incentives, fill information gaps, and minimise interruptions in the supply chain will require no less innovation.11 Proof that antibiotic prescribing contributes to resistance in the individual patient and not just at the societal level is the kind of evidence that needs to be communicated to clinicians.12 Taking a page from the Five Million Lives campaign and the work of the World Alliance for Patient Safety, much more can be done to bolster diagnostics and surveillance of resistance patterns, reduce demand from patients for unnecessary antibiotics, and help standardise optimal dosing regimens and treatment times.
The EU-US Transatlantic Task Force must rise to this complex challenge and define its solution in global terms. Nothing less than the future of medicine, from organ transplants to chemotherapy, is at stake, and there will be no second chances.
Cite this as: BMJ 2010;340:c2071
Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf and declare: (1) No financial support for the submitted work from anyone other than their employer; (2) No financial relationships with commercial entities that might have an interest in the submitted work; (3) No spouses, partners, or children with relationships with commercial entities who might have an interest in the submitted work. (4) AS directs the Strategic Policy Unit of ReAct—Action on Antibiotic Resistance—and was chair of the WHO/World Alliance for patient safety working group on antimicrobial R&D. OC is the chairman and founding executive director of ReAct and served as co-chair of the WHO/World Alliance for patient safety working group on rational use of antimicrobials.
Provenance and peer review: Commissioned; not externally peer reviewed.