Sustainable Global System Might Avert Antibiotic Resistance

Laurie Barclay, MD

November 18, 2013

The entire structure of healthcare delivery for effective antibiotics, including research and development, distribution, and rational use, must be reengineered to avert the looming global threat of antibiotic resistance, according to a Lancet Infectious Diseases Commission report published online November 17 in the Lancet Infectious Diseases.

The report, authored by 26 experts from around the world, offers a comprehensive global overview of the growing problem of antibiotic resistance, leading causes and repercussions, and critical areas needing urgent action. Release of the report immediately precedes European Antibiotic Awareness Day and the Centers for Disease Control and Prevention's (CDC's) Get Smart About Antibiotics Week, which begins November 18.

"The causes of antibiotic resistance are complex and include human behaviour at many levels of society; the consequences affect everybody in the world," lead author Professor Otto Cars, MD, from Uppsala University in Sweden and ReAct Action on Antibiotic Resistance, said in a news release. "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."

Factors promoting development of antibiotic resistance include dramatic surges in antibiotic use in agriculture as well as in medicine; lack of adequate regulatory controls, treatment guidelines, and patient awareness; and a dire shortage of new antibiotics that could treat multidrug-resistant bacterial infections.

"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," Dr. Cars said in the release. "Addressing these problems will require nothing less than a fundamental shift in how antibiotics are developed, financed, and prescribed."

Antibiotic resistance is garnering increasing worldwide attention, thanks in part to recent bulletins and alerts from the World Health Organization, the CDC, and the UK's Chief Medical Officer. However, national and international coordination and collaboration to solve the problem are still lacking, especially at the political level, according to the report authors.

New Drug Development and Financing Strategies Urgently Needed

Recent factors hindering the development of desperately needed new antibiotics include scientific challenges, low financial returns compared with many other medicines such as those used to treat chronic disease, and the regulatory environment.

The report therefore mandates new ways of financing drug development not only through national and international political commitment and investment but also by revamping the infrastructure of academia and industry to confront the threat of antibiotic resistance.

Anticipation of large-volume sales typically fuels investment in new drug development, but for antibiotics, this strategy can backfire, as aggressive marketing and sales activity lead to overprescription, thereby increasing the risk for bacterial resistance. Compounding the problem is that many countries have financial incentives for physicians and healthcare systems, which encourage antibiotic overprescription.

New, innovative, and sustainable financing models should uncouple research and development investment from revenue returns, the report authors suggest. Incentives should be realigned using effective feedback loops. Because of the presently insufficient infrastructure and innovative capacity, academic research institutes and small- and medium-sized enterprises worldwide should greatly expand their role in antibiotic discovery.

Inappropriate Antibiotic Usage Must Be Curbed

Antibiotic usage needs to be optimized so that these medications reach people with the greatest need, particularly sick children in poor countries. Simultaneously, the report authors warn, inappropriate antibiotic usage must be minimized. For example, using rapid point-of-care diagnostic tests can identify pathogens and their antibiotic sensitivity, thereby improving efficacy and safety.

An additional source of emerging bacterial resistance is nontherapeutic use of antibiotics in animals. However, an outright ban on nonprescription sales of antibiotics could block access to antibiotics for some of the poorest and most marginalized populations worldwide. Because of inadequate sanitation, sewage, and clean water supply, risk for infection is increased in these groups. Effective solutions must consider local resources and cultural beliefs while empowering and involving patients as well as clinicians.

"Antibiotic resistance is a complex ecological problem which doesn't just affect people, but is also intimately connected with agriculture and the environment," Dr. Cars said in the release. "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."

Global Effort Needed to Combat Antibiotic Resistance

In an accompanying editorial, Martha Gyansa-Lutterodt, from the Ministry of Health Ghana, Infection Prevention and Control Policy, notes that monitoring of antibiotic use in Ghana is poor, and counterfeit medical products abound.

The capability to link results of laboratory diagnostic tests to selection of medicines is lacking, and there is a strategic need to build capacity for research into key issues surrounding antibiotic resistance.

"To improve surveillance of resistance and drug use, a small percentage (at least 2%) of funds from President's Emergency Plan For AIDS Relief (PEPFAR) or the Global Fund to Fight AIDS, Tuberculosis and Malaria could be used across their areas of operation," Gyansa-Lutterodt writes.

"[W]hen it comes to any new antibiotic, there must be responsible access to medicines with stringent regulatory mechanisms to curtail misuse. In effect, any new antibiotics would need similar distribution mechanisms to those in place for dangerous drugs," she concludes.

In a linked comment, Simon J. Howard and colleagues from the Office of the Chief Medical Officer, London, United Kingdom, agree that a global response is needed to limit antibiotic resistance. Furthermore, the importance of hand washing and other hygiene measures should not be overlooked.

"In the UK, a cross-government antimicrobial strategy has been launched," Howard and colleagues write. "The key elements are: improvement of infection prevention and control practices in human and animal health; optimisation of prescribing practice; improvement of professional education, training, and public engagement; development of new drugs, treatments, and diagnostics; better access to and use of surveillance data; better identification and prioritisation of research into antimicrobial resistance; and strengthened international collaboration. The UK Government is working alongside other governments under the auspices of the [World Health Organization] to improve global antimicrobial stewardship and surveillance."

Mark Young, from the United Nations Children's Fund, New York City, and colleagues also stress the need for preventive measures to improve child survival in their accompanying comment: "With political will and coordinated engagement of public, private, and civil society sectors, the world can fulfil the promise to give every last child the opportunity to survive and thrive," they write. "The availability of good quality antibiotics effective against childhood pneumonia and neonatal sepsis will be essential to success."

Some of the report authors have various financial disclosures involving the National Institute of Health's Fogarty International Center, the Robert Wood Johnson Foundation (Investigator Award in Health Policy Research), a SIDA-supported grant to ReAct–Action in Antibiotic Resistance, an European Commission FP7 grant (BacAttack), an Innovative Medicines Initiative grant (Predict TB), Helperby Therapeutics Ltd, the International Society of Chemotherapy, and/or various companies involved in the development of diagnostics and antibiotics for methicillin-resistant Staphylococcus aureus. The commentators have disclosed no relevant financial relationships.

Lancet Infect Dis. Published online November 17, 2013. Article abstract, Editorial extract, Howard comment extract, Young comment

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