New hope to rescue the livesaving antibiotics

Story Jan 10, 2019
Antimicrobial resistance is one of the greatest known threats to human health. Recent research shows that insufficient treat­ment of wastewater from pharmaceutical plants is an important contributor, but so far, the problem has been difficult to tackle. Now there is new optimism, with talk of tougher regulation and new incentives. Will 2019 mark a turning point?

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This article is written by Maria Sköld and was originally published in WaterFront #3-4 2018.
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The World Health Organization warns that antimicrobial resistance, AMR, could quickly wipe out many of past decades’ health gains. It is expected that by 2050, more people could die from AMR than from cancer and diabetes combined. Over-subscription of antibiotics to humans and overuse in intensive animal farming are two main culprits behind the worrying trend, but in recent years it has been discovered that wastewater emissions from pharmaceutical production play a larger role than previously assumed. Back in 2007, researchers from University of Gothenburg, Sweden, became the first to discover shockingly high levels of antibiotics in rivers downstream from a wastewater treatment plant in India’s pharmaceutical hub, Hyderabad. The concentration of antibiotics in the water was not only the highest ever recorded in the environment, it exceeded what can be found in the blood of patients taking the drug.

 

Carl-Fredrik Flach

Ten years later, the team continues to study the polluted environments, not least how the discharges contribute to the spread of AMR. “There’s no doubt that having such high concentrations of antibiotics released into the environment drives antimicrobial resistance and selects for resistant bacteria,” says researcher Carl-Fredrik Flach, associate professor at the Centre for Antibiotic Resistance Research (CARe) at the University of Gothenburg. 
 
He is particularly worried about discoveries implying that antibiotic resistance genes found in pathogens may originally stem from harmless environmental bacteria, and that such movements of genes and in turn emergence of resistant bacteria may be favored in these environments. With today’s travel patterns, it doesn’t take long for resistant bacteria to spread throughout the world. Carl-Fredrik Flach believes that antimicrobial resistance must be tackled as a high-priority global risk rather than solely as a local problem for the manufacturing countries.
 
In the wake of the World Trade Organisation’s 1994 agreement on trade-related aspects of intellectual property rights (TRIPs), India and China have emerged as the international pharmaceutical giants, producing the vast majority of the world’s medicines. As a result, the cost of medicine has come down, but the price has often been paid by the production countries’ watersheds and the people living close to them. India’s severe water pollution crisis has many sources, but the country’s manufacturing industry is certainly one of them. According to a 2015 report from the Indian government, half the country’s rivers are now polluted, and the number of contaminated waterways doubled between the years 2010 and 2015.
 
In Hyderabad, some effects are visible even to the eye. The area was once famous for its abundance of pure lakes but today many of them are foaming with toxic waste. In a report commissioned by the Nordic bank Nordea, it is described how villagers living close to the Dharani Nagar lake have been forced to evacuate their homes after 50 houses became covered with toxic foam. Researchers working on the report also collected testimonials from locals about thousands of dead fish washed ashore and about school children developing rashes and eye conditions.
 
Still, the most serious long-term consequences may not yet be fully understood. There is concern that chemicals are seeping into the groundwater and the Gothenburg team has found antibiotics in ground wells close to manufacturing sites. Local groups, quoted in two Nordea funded studies, complain that the growing body of academic and NGO reports about the dangers of water pollution in Hyderabad are not taken seriously enough. Companies continue to discharge insufficiently treated wastewater into the area’s waterways without the authorities being able to handle the situation. Activists fear that the situation could get even worse as India is seeking to further expand the national pharmaceutical industry, which is already one of the fastest growing segments of the Indian economy, employing 2.5 million people.  According to Make in India, a government-sponsored initiative to attract investment, the cost of producing pharmaceuticals in India is almost 50 per cent lower than in western Europe.


ANTIBIOTICS

Antibiotics are medicines used to prevent and treat bacterial infections. After 1945, they have spread rapidly around the world, revolutionizing modern medicine. Antimicrobial resistance: Anti-microbial resistance occurs when a microorganism evolves to resist the effects of an antimicrobial agent. Globally about 700,000 people die of resistant infections every year because available anti-microbial drugs have become less effective at killing the resistant pathogens. Source: UNEP

 

At the same time, there is another, competing, trend. The national Indian government is starting to speak up about the dangers of antimicrobial resistance, with the Environment Ministry classifying the pharmaceutical industry as a “red cate­gory”, over concerns about hazardous waste from production. Among international organizations, the government’s ambitious National Action Plan on Anti-Microbial Resistance from 2017 is often cited as a benchmark example.
 
“The situation is complex,” says Dulce Calçada, researcher at Access to Medicine Foundation, a non-profit that guides and incentivizes pharmaceutical companies to do more for people without access to medicine.

Dulce Calçada


“Traditionally, regulation on industrial wastewaters focuses on water quality parameters that should safeguard environmental integrity. There are currently no antibiotic discharge limits aimed at preventing development of antibiotic resistance in the environment. Not anywhere in the world, to the best of our knowledge.”
 
Within India, there are calls for the country to become the first to introduce limits also to pharmaceutical effluents. The Central Pollution Control Board, which is monitoring the implementation of the National Action Plan, is now working on draft standards for the industry which could come into effect in 2019. The Access to Medicine Foundation started to work on antimicrobial resistance in 2016 and published the world’s first independent benchmark of pharma action on the topic in January 2018. According to the organization’s Director of Strategy, Damiano de Felice, there is definitely a shift in attitudes. “Antimicrobial resistance has now become a global issue and that has created new expectations. Pharmaceutical companies begin to feel the pressure and see the advantages of developing and implementing stronger risk management strategies to prevent antibiotic discharge in the environment” he says.
 
It was in 2016 that antimicrobial resistance really came into the international limelight. That year, more than 100 pharmaceutical companies and industry associations signed the Industry Declaration on AMR at the World Economic Forum in Davos in January. A few months later, 13 companies committed to the more detailed Industry Roadmap for Progress on Combatting AMR. In May, economist Jim O’Neill published a Review on AMR with a chilling description of an international health crisis many had so far managed to ignore. Soon after, in a political declaration from the UN General Assembly, governments promised to take action. Various countries, international organizations and UN agencies have produced their own strategies, as have the G7 and G20 groups.
 
All these activities are important, argues Damiano de Felice, since they build momentum and clarify expectations. Still, most activities remain based on voluntary contributions and that may not be sufficient to trigger a real shift in the industry: “Many companies point to the high cost of implementing better waste treatment technologies and a lack of incentives, such as procurement agencies rewarding responsible manufacturing practices,” he says.
 
In the debate over whether the voluntary approach will be enough, a common argument against regulation is a lack of scientific agreement on which emission levels that could be considered safe. But Carl-Fredrik Flach argues that ongoing research shows that it is indeed possible to establish acceptable emission levels. His research team from Gothenburg University has also published a list of predicted “no effect concentrations” regarding resistance selection for 111 antibiotics, an approach that was highlighted in the AMR Review from 2016 as a good starting point for defining discharge limits.
 
An important step was taken last September, when the AMR Industry Alliance – the coalition coordinating implementation of the commitments made by companies in 2016 – published a list of recommended antibiotic discharge targets. The Alliance now encourages its member companies to work towards ensuring that these limits are enforced in their manufacturing operations. “We need regulations on emission levels and the producers must become transparent about what they do. Some companies claim to have emission restrictions in place but since they never disclose any details, there is no way for us to know,” Carl-Fredrik Flach says, adding: “Without increased transparency, companies don’t need to reveal where they get their substances, so it’s impossible to know where a product is really produced. But I’m optimistic that this is beginning to change –hopefully we will soon have regulations in place.”