The relationship between pharmaceuticals and the environment is often underestimated, yet it carries increasingly serious consequences. Among these, antimicrobial resistance stands out—a phenomenon projected to cause 10 million deaths per year by 2050. This issue isn’t new: back in 1956, Dr. Henry Welch of the FDA referred to a “third era of antibiotic therapy,” focused on drug combinations capable of combating even the most resistant bacteria.
Antibiotic resistance: a growing concern
The evolution of antibiotics has progressed from narrow-spectrum agents like penicillin to broad-spectrum treatments such as Pfizer’s Terramycin, and later to synergistic combinations like Sigmamycin, developed to fight bacteria that had become immune to older drugs. However, this progression has also produced overlooked environmental side effects.
The causes of antimicrobial resistance are varied: misuse of antibiotics by patients and doctors, particularly in low-income countries, plays a major role. But a lesser-known factor is the inability of wastewater treatment plants to eliminate pharmaceutical residues, which then enter the environment.
Eco-pharmacovigilance: monitoring drug impact on the environment
To tackle this issue, the concept of eco-pharmacovigilance was introduced, aiming to evaluate the environmental impact of drugs as early as the registration phase. Since 2006, European regulations have required such assessments for all active pharmaceutical ingredients. These substances, excreted through urine and feces, reach wastewater treatment plants in unchanged or active metabolite forms. Yet these facilities often fail to completely remove them.
As a result, trace amounts of pharmaceuticals have been detected in rivers, lakes, seas, groundwater, and even drinking water. Furthermore, the use of sewage sludge as fertilizer can reintroduce these contaminants into the soil, creating a vicious cycle of pollution.
The EU directive and industry responsibility
The new EU Urban Wastewater Directive mandates the upgrading of treatment plants to include quaternary treatment, the only method capable of effectively removing pharmaceutical contaminants. Under the Extended Producer Responsibility (EPR) principle, pharmaceutical and cosmetic companies must finance at least 80% of these costs.
Cosmetic companies can offset the expense by raising prices, but pharmaceutical companies—bound by regulated pricing—face severe economic risks. Several firms have already filed a complaint with the EU Court of Justice, warning of the potential disappearance of essential drugs like tamoxifen, metformin, amoxicillin, and levetiracetam.
The cost and uncertainty of plant upgrades
Estimates for the cost of upgrading treatment plants vary significantly:
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€1.21 billion, according to the European Commission;
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€4.42 to €5.12 billion, according to the German Environment Agency;
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Up to €6.1 billion, with annual operational costs reaching €800 million, according to Utilitalia and IRSA-CNR.
Given these figures, plant upgrades seem distant, while no new class of antibiotics has been discovered since the 1980s. A promising alternative may lie in the development of vaccines against hospital-acquired infections, now in early clinical stages, targeting pathogens like Staphylococcus aureus, Mycobacterium tuberculosis, Escherichia coli, Pseudomonas aeruginosa, Candida albicans, Clostridium difficile, and Streptococcus pneumoniae.