Drug residues – new ways to monitor a growing threat

All around the globe, human and animal medicines save lives. But, at the same time, the residues from many drugs continue to be a menace.

According to the World Health Organisation, the overuse of antibiotics presents “one of the biggest threats to global health, food security, and development today” - with antimicrobial resistance (AMR) causing more deaths across the world in 2019 than HIV/AIDS or malaria.

But residues from many other pharmaceutical drugs are also increasingly prevalent – making their way from humans to the water cycle, where they contaminate aquatic life and feed undesirable metabolites and other compounds back into our food.

Governments are meanwhile under increasing pressure to respond to academic research and evidence from so-called ‘citizen scientists’ by expanding their requirements for drug residue monitoring and analysis. In the coming years, this could present the testing industry with both challenges and opportunities.

AMR in agriculture, the environment and food

As the US Centers for Disease Control and Prevention states, “any time antibiotics are used, the drugs can contribute to the development of antibiotic resistance.” But the use of antimicrobial drugs in agriculture is particularly problematic.

The UK Parliament’s Environmental Audit Committee (UKEAC) blames “the intensive farming of livestock and poultry” for contributing to poor water quality. Meanwhile, research from a coalition of British activist groups last year found higher levels of antibiotic and bacterial resistance downstream from five out of eight intensive units – while none of four higher welfare operations studied produced the same effect. A BBC News article about the report also quoted Cardiff Water Research Institute director Professor Isabelle Durance as saying it was accepted that faecal matter entering water bodies could carry drug-resistant bacteria and genes – but "extremely difficult" to link bacteria in rivers to a specific source. ‘Factory’ farming methods have also been blamed for contributing to AMR in other ways, since keeping animals close together can help spread disease, and lead to antibiotics being given preventively to whole herds or flocks. 

Another way that antibiotic residues from agriculture find their way into watercourses is through the use of animal sewage sludge, or slurry as a fertiliser – meaning that rainfall run-off carries antibiotic residues and other chemicals contained in faecal matter into streams and rivers.

A meta-analysis published last year by Germany’s Martin Luther University also reported that UK soil fertilised with manure or slurry contained up to ten times the European Union (EU) recommended concentrations of tetracyclines, while significant concentrations of fluoroquinolones were also detected in Austrian soil. “These substances can eventually reach the food chain due to root uptake”, added the report, which also noted “an accumulation of tetracyclines and sulfonamides (in plants) in China, Germany, and Spain.”

Aside from their effects on crop soils and the wider environment, the use of antibiotics in animal husbandry can also lead directly to ‘carryover contamination’ into animal products intended for consumption by humans. This can also happen in several ways - including when farmers and vets use medicated feed mistakenly, utilise the drugs in an unapproved or ‘extra-label’ (unprescribed) manner, make them part of a feeding regime (for example, as growth promoters), or fail to observe drug withhold clearance times before slaughter.

Wastewater

Another common way for drug residues to enter the environment and our food is through wastewater. A 2021 report from a group of Spanish scientists observed that the world’s water treatment works are not designed to filter out residues from antibiotics and other drugs excreted by humans, and “so they reach practically all environmental matrices, even tap water.”

“As drugs are designed to produce pharmacological effects at low concentrations,” the report added, “they are capable of producing ecotoxicological effects on microorganisms, flora and fauna… on human health (and)… along the food chain.” The UKEAC meanwhile heard evidence of “sewage treatment works and the rivers they discharge into… becoming breeding grounds for antimicrobial resistance” - with 11 of 97 UK coastal waters studied containing E. coli resistant to antibiotics, and “surfers… three times more likely than non-surfers to have antibiotic-resistant bacteria in their gut.” Research into sharply declining bonefish stocks off the coast of Florida also found that all 93 fish sampled tested positive for at least one pharmaceutical – more than half of them at levels “above which we expect negative effects”.

Threats from other drugs

Antibiotics are far from the only drugs whose residues cause harm. A study last year of more than 258 rivers on all seven continents discovered traces of diabetes- and anti-epileptic drugs at 50 per cent or more of the sites, while cetirizine (an antihistamine) and citalopram (an antidepressant) were detected on every continent except Antarctica. A “sizeable number” of locations also recorded at least one Active Pharmaceutical Ingredient (API) at a level considered harmful to aquatic organisms, prompting report lead author John Wilkinson to state: “If I were a fish living in some of these rivers, I’d be worried right now.”

Fuelled by the worldwide increase in their use caused by the Covid-19 pandemic, antidepressant and antianxiety medicines are a particularly fast-emerging and concerning source of contamination in the world’s water cycles. According to Mexican research, many fish and molluscs have bioaccumulated different antidepressant drugs in their tissues, while a Swedish tracking study found that fish exposed to oxazepam became bolder, had larger territories and were generally more active.

Current – and future? - regulation

Concerns about antimicrobial resistance have prompted new regulation on both sides of the Atlantic in recent years. In 2017, the US issued the federal Veterinary Feed Directive, which mandated veterinary oversight when medically important antibiotics are given to food animals. In the European Union, maximum residue limits for hundreds of pharmacologically active substances in foodstuffs of animal origin have been in place for more than a decade. However, these were reinforced in January, when the The Veterinary Medicinal Products Regulation introduced several new measures aimed at controlling AMR.

Many research groups studying veterinary and pharmaceutical residues have called for more action to be taken on the issue – including reducing drug use and increased monitoring. Legislators have added to the pressure on governments to act by making similar recommendations – with the UKEAC also celebrating “The important role that citizen scientists have played in bringing the issue of poor water quality in rivers to national attention.” However, it also warned of “the danger of disillusionment if regulators then failed to take action” in response.

The EU has also responded to the growing pressure by introducing a six-step Strategic Approach to Pharmaceuticals in the Environment, promoting data monitoring, reduced manufacturing emissions, and improved wastewater treatment – all of which could lead to more work for testing laboratories.