The fight against drug-resistant infections

Posted On: 
11th March 2019

Antimicrobial resistance is one of the 21st century's greatest health threats. To manage this global challenge, we urgently need more data, writes Lef Apostolakis from POST

Unless AMR is effectively managed, estimates predict the death toll in Europe rising to 333,000 per year by 2050, or ten million globally
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ln 1928, the discovery of Penicillin revolutionised the ‘war on germs’. It introduced the world to antibiotics, saved millions of lives, and propelled modern medicine into a new era. Over the past century however, microbes have been developing antimicrobial resistance (AMR), and microbial infections have become drug-resistant and more difficult to treat.

In Europe alone, over 33,000 deaths every year are attributed to drug-resistant bacterial infections. Unless AMR is effectively managed, estimates predict the death toll in Europe rising to 333,000 per year by 2050, or ten million globally. Of course, we are not just waking up to this challenge. The Parliamentary Office for Science and Technology (POST) has published three peer reviewed analyses on AMR over the last seven months: a POSTnote on AMR and immunisation, a POSTnote on reducing UK antibiotic use in animals, and  one reviewing reservoirs of AMR.  

WHAT IS POST? 

The Parliamentary Office for Science and Technology is a bicameral body within UK Parliament that bridges research and policy. Its flagship briefings, called "POSTnotes", are impartial, non-partisan, and peer-reviewed.

Parliament’s Health and Social Care Committee concluded an inquiry in October which suggested AMR should be treated as a “top five policy priority”. The UK has also just come out of a five-year AMR strategy, developed by the Department of Health and Social Care, which has successfully increased the monitoring of hospital laboratories from 82.7% to 97%, and decreased the use of antibiotics in animals by 40%. 

Gaps in our knowledge remain however, and while we may have a good understanding of how AMR works, and know where it develops – in humans, animals, or in the wider environment – data is sparse and can’t adequately inform public health policy. 

How do microbes become resistant? 

The development of resistance to antimicrobials is a result of the natural process of evolution.  

Let's take bacteria for example, which reproduce by division. Bacteria will produce a copy of their DNA before dividing into two. These copies however are not always identical; mistakes called mutations often occur and sometimes these mutations can bring new traits, such as resistance to an antibiotic. 

Antibiotics kill bacteria that are not resistant, leaving behind only those that carry the resistance mutation. Free from competition over space and nutrients, the resistant bacteria spread, dominating their environment.   

More importantly, AMR can also spread horizontally, from one bacterium to its neighbor, without the need for reproduction. This happens when AMR mutations are located on parts of the DNA that can move within and between organisms. These mobile genetic elements can spread the trait between neighboring bacteria of the same species, and cross from one species to another. 

These attributes make AMR a major risk to human health. Disease-causing microbes (known as pathogens) become more difficult to kill, making infections more difficult to treat. Microbes that are normally not pathogenic (referred to as opportunist) can also survive antibiotic treatments. Taking advantage of the lack of competition, they multiply or even migrate in other organs in the human body, causing health complications.
  
Where does AMR develop? 

Microbes can be found everywhere, in humans, in animals, and the wider environment, and AMR can develop in any one of these areas which we refer to as ‘reservoirs’. Antimicrobial use in human medicine is believed to be the main driver of AMR in the human reservoir. The same can be said for veterinary medicine and AMR in the animal reservoir. Exposure to waste products from humans, animals, and industry can likewise drive the development of AMR in microbes of the environment.  

Understanding where AMR can develop is important, because resistance can theoretically move from one reservoir to another. Studies have suggested transfer occurring through a number of avenues; from close contact between people and animals, to bathing in coastal waters. We need to be able to answer how often such transfers occur if we are going to be able to quantify the public health risks. 

Despite this urgent need, a 2018 review trying to quantify drivers of antibiotic resistance in humans found that 89% of studies exclusively considered human data, and only 11% considered animal and environmental reservoirs.  

Keeping AMR in check 

So far, efforts to quantify where AMR occurs have focused on the human reservoir. In the UK, the English Surveillance Programme for Antimicrobial Utilisation and Resistance monitors the use of antibiotics in primary and secondary medical care, through the collection of data by Public Health England’s (PHE) Antibiotic Prescribing Data Warehouse and human health data science company, IQVIA.

It also collects data on AMR from hospital laboratories, which are reported to a national database - the PHE’s Second Generation Surveillance System – and now covers 97% of hospital laboratories in England.  

Structures also exist for the surveillance of AMR in animals. The Veterinary Medicines Directorate (VMD) annually presents combined data on veterinary antibiotic sales, antibiotic usage, and antibiotic resistance in bacteria obtained from food-producing animals in the UK. However, data is not available in all food producing sectors, and sales data does not reveal the quantity of antibiotics used per species. The VMD is working with a wide-range of stakeholders to improve the collection of antibiotic usage data.
  
Currently, there are few structures monitoring AMR in the environment, even though antimicrobial residues can find their way to the environment through hospital and urban wastewater, and soils treated with animal manure, for example. Sites where antimicrobials are found in high concentration could pose public health risks. 

Planning for the future 

The UK’s five-year AMR strategy, which concluded in 2018, successfully met several objectives.  However, there is widespread consensus for greater integration of surveillance data from across all three reservoirs. The UK One Health Report also called for the revisiting of some of the strategy’s commitments, as it suggests changes to access and use of surveillance data have not been adequate. There are also some concerns about the lack of structural, statutory surveillance dedicated to assessing the level of AMR in the UK’s environment.

In January 2019, the Department of Health and Social Care published a 20-year vision for AMR alongside a five–year action plan which will, “deepen understanding about AMR in the environment.”  So far, a network of 23 partners has been awarded funding with the aim to identify robust, measurable surveillance indicators and methodologies for assessing environmental AMR levels.  

With similar international initiatives arriving at the same conclusions (such as the EU One Health Action Plan against AMR), the need for a global coordinated approach is becoming widely accepted. To manage this global challenge, we need to urgently further our understanding of AMR. 

Lef Apostolakis is the Communications Manager for POST. This article was based on the POSTnote Reservoirs of Antimicrobial Resistance by Peter Border and Alana Dowlin