No legal limits

Beyond better monitoring, experts say the real issue is regulation since there are no legal limits on antibiotic levels in the environment — meaning drugmakers can, in theory, pollute with impunity.

“The standards of quality of the water environment regarding macrolide antibiotics [including azithromycin and erythromycin] are not defined in Croatian or EU laws,” state water utility Hrvatske Vode said in a statement.

Nor are there regulations on antibiotic levels in wastewater from manufacturing.

In a 2018 report by the US Centers for Disease Control and Prevention, the UK Science and Innovation Network and the Wellcome Trust, experts warn of the perils of too little information on AMR in the environment — and on the manufacturing of antibiotics in general.

Not only is there little published data on volumes of active pharmaceutical ingredients produced globally each year, or even where the ingredients are produced, there are no international standards for antimicrobial limits in wastewater, they say.

“Specifically, greater clarity is needed on the risk to human health in order to prioritise action,” the report says.

The first independent assessment of how drugmakers are responding to the AMR threat was conducted last year by the Access to Medicine Foundation, a Dutch non-profit that lobbies the pharmaceutical industry to do more for poor people.

It showed that only eight of 30 surveyed companies set limits on antibiotics released into the environment — and none published the amounts they actually pump out.

“Regulatory authorities in the EU don’t require this information to be shared,” Suzanne Wolf, director of communications at the Access to Medicine Foundation, told BIRN.

In Sweden, which leads the way in Europe in addressing the environmental causes of AMR, the government has mandated the Swedish Medical Products Agency (MPA) to lobby at the EU level for tighter controls on environmental pollution from drug making.

Existing regulations cover drug quality and safety but not emissions from factories, said Kia Salin, an environmental strategist at the MPA.

“The pharmaceutical industry is highly against this implementation,” Salin said. “They even said that they will check this by themselves voluntarily, but there is still evidence of high levels of pharmaceutical substances in the environment around the manufacturing sites, outside and inside Europe.”

The pharmaceutical industry is highly against this implementation. – Kia Salin, Swedish Medical Products Agency

Asked about the situation in Croatia, Salin stressed the importance of independent monitoring of emissions from drug companies.

“Independence should be one of the main focuses,” she said. “For several years, we have been arguing about this, at several seminars at the international level, and nothing has changed. Industry is constantly against it.”

Given the information and policy vacuum, it is left to scientists and researchers to try to get a handle on the problem.

In May, the largest global study of its kind measured antibiotic concentrations in 200 rivers in 90 countries.

Alistair Boxall, an environmental scientist at the University of York who coordinated the study, told BIRN that manufacturing pollution was clearly detected in some African and Asian countries, but not so much in European rivers.

Still, some European locations such as the Danube channel in Vienna had “fairly high” antibiotic levels, he said.

“We compared concentrations with the proposed safe thresholds in terms of risk for antimicrobial resistance development and there were some sites in Europe exceeding those thresholds,” he said, adding that the European data is still being analysed.

In March, the European Commission adopted a Strategic Approach to Pharmaceuticals in the Environment recommending six actions to take, including gathering better data, reducing emissions from manufacturing and improving wastewater treatment.

But Wolf from the Access to Medicine Foundation said: “Unless identified actions are regulated, chances are that the problem will not be improved”.

For the MPA’s Salin, the commission’s strategy was a disappointment.

“It has no real proposal on how we should tackle the problem,” she said. “It’s more about how we should discuss the issue for another decade or so.”

The University of Gothenburg’s Bengtsson-Palme said the big frustration is that environmental pollution is the easiest part of the superbug puzzle to solve.

“The environmental cause of AMR plays the smaller role, opposed to misusing antibiotics in public health and agriculture,” he said. “But releasing antibiotics into the environment for no reason other than it is a little bit less costly doesn’t have any benefit.”

In 2015, he and his colleague Larsson created a list of “border” concentrations for more than 100 antibiotics high enough to trigger antimicrobial resistance. The idea was to help regulators identify levels where antibiotic pollution becomes dangerous.

“If we can’t do anything about that, I can’t imagine we’ll be able to do anything about overusing [antibiotics], where it’s not just money but human and animal life at stake,” he said.

‘Unintelligent Monitoring’ Across Europe, only two antibiotics — sulfamethoxazole and sulfamethazine — are widely monitored in rivers by national authorities, according to a 2018 report by the European Commission’s Joint Research Centre. Other antibiotics, if they are monitored at all, are only done so in a few EU countries. Croatia is one of the countries that does monitor three so-called macrolide antibiotics: azithromycin, erythromycin and clarithromycin. Hrvatske Vode, the state water utility, says it monitors these antibiotics in line with a European Commission decision ( 2015/495 ) to create a watchlist of potentially dangerous substances in water. But the monitoring only takes place up to four times a year in the same two locations on the Sava river. The nearest is around 10 kilometres downstream from Pliva’s factory. In most cases, “there were no significant traces of these antibiotics in the water,” Hrvatske Vode said. Alistair Boxall, coordinator of the largest global study of antibiotics in rivers, said it was best practice to collect samples at many different spots on a given river — from six to 20 per city. “The problem with monitoring done by regulatory agencies is that they are still looking at only a few chemicals,” he said. “In the UK, we are spending millions on monitoring the chemicals that we actually don’t use anymore and we are ignoring everything else.” Boxall noted that the EU’s watch list of dangerous substances only contains a few pharmaceuticals. “There is not much intelligence in the current monitoring system,” he said. “Things could be done more thoroughly, like we did in our study, or we can use some advanced analytical methods. That will certainly tell us more about what is going on in our rivers and what we are exposed to.”

Vedrana Simicevic is a Croatian freelance journalist who specialises in science, the environment and social issues. This article was produced as part of the Balkan Fellowship for Journalistic Excellence, supported by the ERSTE Foundation, in cooperation with the Balkan Investigative Reporting Network. Editing by Timothy Large.