By Sharon Atieno

With an estimated 750,000 deaths associated with antimicrobial resistance (AMR), urgent action is needed to prevent further escalation, authors of a new Lancet Series on the issue said during the World Health Assembly.

AMR occurs when bacteria and other microbes evolve to resist the drugs designed to kill them, making treatments especially antibiotics, ineffective.

According to the authors, there is need to ensure sustainable access to antibiotics through intensifying efforts to promote vaccination, access to safe water and sanitation, and hospital infection control. This will reduce infections and the use of antibiotics, which protects their long-term effectiveness.

They also called for expanding access to existing and new antibiotics, which could save many lives lost to bacterial infections and increasing investment in new antibiotics, vaccines and diagnostics that are designed to be affordable and accessible to patients in need globally.

A new modelling analysis as part of a new four paper Series published in The Lancet estimates that improving and expanding existing methods to prevent infections, such as hand hygiene, regular cleaning and sterilisation of equipment in healthcare facilities, availability of safe drinking water, effective sanitation and use of paediatric vaccines, could prevent AMR associated deaths every year in low- and middle-income countries (LMICs).

“Access to effective antibiotics is essential to patients worldwide. A failure to provide these antibiotics puts us at risk of not meeting the UN sustainable development goals on child survival and healthy aging. Effective antibiotics prolong lives, reduce disabilities, limit healthcare costs and enable other life-saving medical actions such as surgery,” Series co-author, Professor Iruka Okeke of the University of Ibadan, Nigeria, says.

“However, antimicrobial resistance is on the rise – accelerated by inappropriate use of antibiotics during the COVID-19 pandemic – threatening the backbone of modern medicine and already leading to deaths and disease which would have once been prevented.”

The new Series highlights how babies, children, the elderly and people with chronic illness are most vulnerable to AMR as they have a higher risk of contracting bacterial infections in general.

A third of deaths in newborn babies, for instance, are caused by infections and half of those to sepsis (body’s extreme reaction to infection including organ failure and tissue damage). Increasingly, the bacteria or fungi which cause these infections are no longer responding to most readily available antibiotics, for example, in a study including 11 countries across Africa, Asia, Europe, and Latin America between 2018-2020, 18% of babies with sepsis did not survive despite being given antibiotics.

According to co-author Professor Joseph Lewnard of the University of California in Berkeley, “Focusing on interventions with demonstrated effectiveness in preventing infections must be at the heart of global action to tackle AMR. Preventing infections reduces the use of antibiotics and reduces selection pressure for AMR so that the drugs will work when they are most needed.”

Novel modeling analysis undertaken for the Series estimates existing infection prevention methods that could prevent deaths associated with AMR infections a year. The analysis estimates that improving infection prevention and control in healthcare facilities including better hand hygiene and more regular cleaning and sterilisation of equipment, could save up to 337,000 lives a year.

Also, universal access to safe drinking water and effective sanitation in community settings could prevent approximately 247,800 deaths annually.

Further, expanding the roll out of some paediatric vaccines, such as pneumococcal vaccines which help protect against pneumonia and meningitis, and introducing new ones, such as RSV vaccines for pregnant mothers, could save 181,500 lives a year.

Co-author Yewande Alimi of Africa CDC, says, “Our findings highlight how public health actions to prevent infections in the first place should be prioritised as a strategy to tackle AMR as these methods have the potential to drastically reduce the number of deaths from AMR-associated infections. If we can focus on improving infection control methods, water and sanitation and vaccination in LMICs then it should be possible to reduce the number of deaths linked with AMR by 10% by 2030.”

The Series also looks at the evidence for preventing resistance emerging in bacteria, alongside preventing infections in the first place.  One of the areas targeted is antibiotic stewardship (reducing the use of antibiotics when the benefit to patients is limited). This is thought to reduce the selection pressure on bacteria to develop resistance, however there is a lack of research in this area.

Co-author Dr Esmita Charani of the University of Cape Town says, “The current limited evidence on the impact of antibiotic stewardship on AMR from low- and middle-income countries does not mean it is not a key intervention that needs focus, but rather makes it difficult to anticipate the effects of antibiotic stewardship in those countries. We urgently need studies to investigate the impact to help inform future policies and interventions fit for different contexts.”

Another key recommendation is rethinking how new antibiotics are discovered and developed with a focus on innovation, affordability and sustainable availability. The traditional model of drug development which are profit driven has failed for antibiotics making them unaffordable. The authors say that public-private partnership could encourage innovation for new antibiotics ensuring affordability and accessibility.

They also call for greater funding for AMR prevention programmes in general, as funding for AMR significantly lags behind that for diseases with smaller burdens such as HIV, malaria, and TB.

Co-author Professor Ramanan Laxminarayan, President of the One Health Trust and Senior Research Scholar at Princeton University, says, “Reducing the impact of AMR through pharmaceuticals is not simply a matter of developing new antibiotics. Unless access and affordability are guaranteed, the vast number of deaths from resistant bacterial infections will continue unabated. Reducing the cost of drug development would help keep antibiotics affordable, as shown by the public-private partnerships for medications to treat malaria and neglected tropical diseases. It’s time for similar tactics in antibiotic development.”

The Series proposes three achievable global targets for 2030 including reducing the mortality rate from AMR by 10% through scaling up public health interventions, reducing human antibiotic use by 20% by reducing use of antibiotics for mild respiratory infections that generally do not require antibiotics and decreasing by 30% the inappropriate use of antibiotics in animals.

The Series also calls for the establishment of an independent scientific body – an Independent Panel on Antimicrobial Access and Resistance – to expand the evidence base for policy implementation and to inform new targets.

“The window of opportunity to ensure our ability to treat bacterial infections is shrinking.  For too long, the problem of AMR has been seen as either not urgent or too difficult to solve. Neither is true. We need immediate action and the tools to do so are widely available.  We hope that this September, the United Nations High-Level Meeting will ensure that there is also the global will to act,” says Professor Laxminarayan.