June 29

Tags

AMR 101

Picture1

In 2015, at the World Health Assembly in Geneva, a massive political commitment was made towards tackling one of the greatest health challenges that few had heard of or considered. Antimicrobial resistance has since risen to the top of the Global Health policy agenda, as international public health institutions, governments, health authorities and private companies attempt to mitigate the risks presented by Antimicrobial Resistance (AMR). If left unchallenged, AMR is projected to be the cause of 10 million deaths by 2050, surpassing cancer and other non-communicable diseases.

AMR2

The average person’s understanding of AMR comes from news articles with attention-grabbing and increasingly panicked headlines of a “post-antibiotic apocalypse” or “superbugs”. While these messages may seem alarmist, the world is precariously close to losing one of the greatest advancements in modern health due to overuse. Antibiotics, first introduced in the 1940s were heralded as “miracles”, changing the way we lived our lives. Gone were the days when an infected cut could lead to death and surgery would go hand-in-hand with serious infection and death. In the years following the mainstream introduction of antibiotics, a new phenomenon was found: loss of susceptibility to the miracle drugs which inhibit or kill bacteria.

The rise of AMR

As early as 1945, Alexander Fleming warned that misuse of the drug could result in selection for resistant bacteria. Resistance to penicillin- the first antibiotic to be used in mainstream medicine- was found within half a decade. While penicillin is still used today, it’s effectiveness has reduced significantly against the range of bacteria which are harmful to humans. This was due to the changing ability of microbes to resist the effect of drugs attacking them. Bacteria, consistently confronted by antibiotics, take every opportunity to learn from these attacks, adapting and growing stronger. As more antibiotics are used to kill off weaker bacteria, the stronger bacteria continue learning and out-surviving the attacks. As their ability to resist attacks grows over time, Antibiotics become less effective and more challenging to use.

Antimicrobial resistance poses a direct challenge to how patients are treated. The greatest problem lies in the case where antibiotics simply won’t work. Patients undergoing surgery in hospitals are routinely given antibiotics before surgery to reduce chances of infection. Most births involve administration of antibiotics. Immunosuppressed patients, such as those with cancer or HIV must use antibiotics to ward off infection. The potential impact of the loss of the ability to use antibiotics for those who need them most would be astronomical.

Of course, having seen headlines like those above and examining the magnitude of resistance, the challenge of AMR seems insurmountable. However, resistance is an expected outcome of using antibiotics; the process is naturally occurring and necessitates introduction of new antibiotics over time. Resistance occurs due to a variety of reasons which make confronting the issue significantly more challenging:

  • Selective Pressure: When confronted by antibiotics, microbes will either die, or if they display resistance, survive. Those which survive will continue to replicate, creating further resistant bacteria, becoming the dominant strain of bacteria in the population as weaker bacteria are killed off.
  • Mutation: Microbes mutate extremely quickly due to a short lifecycle; reproducing every hour, they adapt quickly to changes and the conditions in which they thrive. Mutations which survive in inhospitable conditions will continue to produce other stronger and more resistant bacteria.
  • Inappropriate use: Inappropriate prescribing practices, often driven by patient demand results in overuse of antibiotics. Patients demanding antibiotics for undiagnosed conditions or viral infections provide microbes opportunities to learn from the attacks of antibiotics and result in mutation and selective pressure.
  • Agricultural use: Antibiotics are used in a variety of agricultural activities in vast quantities; often these uses are unnecessary and excessive. Routine antibiotic use in animals promotes growth and prevents infection in animals living in close proximity, however intensive farming provides ample opportunities for resistance.

Confronting resistance thus relies on a concerted effort of both producers and consumer of antibiotics to work together to reduce unnecessary use of antibiotics, optimize the necessary use of antibiotics, and promote development of new antimicrobials to defeat infections.

 

Fighting AMR

There are several avenues which are being pursued to confront AMR, each of which is necessary to guarantee continued use of lifesaving drugs. A few of these are highlighted below:

  • Preventing infection reduces the amount of antibiotics that are used and reduces opportunities for bacteria to develop resistance. Prevention necessitates the use of vaccination and good sanitation practices.
  • Ensuring antibiotics are used appropriately. We need to educate populations as to the costs and benefits of using antibiotics, so that patients do not demand antibiotics when they are not necessary. There are circumstances when antibiotics should and must be used; unfortunately, misconceptions about antibiotics and their mechanisms results in use outside of clinically supervised settings. In many countries, antibiotics are more readily accessible due to their status as an OTC drug instead of prescription only.
  • Identify when antibiotics should be used with diagnostic tools. Easy to use diagnostic tools can help identify if illness is related to bacteria, a virus, or parasite. Antibiotics work only with bacteria, with no mechanism for action against viruses or parasites. By verifying that a bacterial infection is the cause of illness in a patient, use of antibiotics may be better targeted.
  • Improving surveillance and research on AMR. Monitoring resistance to antibiotics is crucial to identifying which antibiotics should be used at what time and where. Surveillance data can be used to improve patient health, inform policies and assist in responding to health emergencies. At the global level, surveillance provides an early warning system for emerging resistance and helps identify how to mitigate the associated risks.
  • Limiting use of antibiotics in farming and food production. While antibiotic use in animals is necessary to promote food security, most countries have few limitations on the quantity of antibiotics and type which may be used in animals. Quantities of antibiotics administered should be regulated, with food products monitored for antibiotic by-products.
  • Developing new classes of antibiotics will permit future generations have access to medicines which may be effective against existing and future pathogens. With the current antibiotic portfolio becoming less effective over time, investment is needed to improve and accelerate R&D where not necessarily commercially viable.

The interventions mentioned above are a handful of the initiatives which may be undertaken to tackle AMR globally. While these are ambitious goals, these tasks are among a much larger group of priorities which the global health community must address to tackle AMR.

“No country can safeguard itself from resistant bacteria unless the world collectively heeds the call.”

Ms Malebona Precious Matsoso, Director General, Department of Health, South Africa

 

PATH and AMR

My assignment at PATH is to identify where countries are facing barriers in implementing policies to confront AMR and assist in developing a toolkit which may operationalize AMR plans. Identifying which initiatives may have the greatest impact is among the most challenging components; AMR interventions should complement the existing health landscape and ideally be cost-neutral. While each country must confront the issue based on the resources available and local context, the interconnected nature of AMR will necessitate an integrated approach internationally.

GSK and AMR

Following an industry-wide commitment to tackling AMR, GSK implemented a number of policies and initiatives which have been highly successful in responding to changing availability of antibiotics. Recognizing the need for private-sector investment in responding to AMR, GSK has invested heavily in R&D to find a new class of antibiotics, implement good antibiotic stewardship policies, engage in antimicrobial surveillance, and decouple antibiotic sales from financial incentives.

GSK’s engagement in AMR has been recognized by the Access to Medicines Index as the highest ranking in almost every indicator worldwide. Leading the industry with its antimicrobial R&D pipeline, GSK currently has 55 projects in place, 40 of which target priority pathogens and 12 new vaccine candidates. Through continued engagement in AMR, GSK is continuing to contribute to challenging one of the greatest public health challenges of our generation.

 

Want to know more?

 


Sources:
https://amr-review.org/sites/default/files/160525_Final%20paper_with%20cover.pdf

https://amrbenchmark.org/wp-content/uploads/2018/04/Antimicrobial-Resistance-Benchmark-2018.pdf

https://www.cdc.gov/drugresistance/about.html

http://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance

https://amrbenchmark.org/industry-performance/

NB: The views represented in this blog are those of the writer and not of GSK or PATH.