Antibiotics and their transformation products in the aquatic environment in the context of antimicrobial resistance

Introduction

Pharmaceuticals and personal care products (PPCPs), including antibiotics, are now recognised among the emerging contaminants of greatest concern for the protection of aquatic ecosystem quality and public health. Their occurrence in the environment reflects patterns of consumption and use in both human and veterinary medicine, as well as the often limited efficiency of wastewater treatment systems.

In recent years, international reports have documented a reduction in veterinary antibiotic consumption between 2014 and 2019, associated with the implementation of antimicrobial stewardship policies (WOAH, 2023). However, the subsequent increase observed during the 2019–2021 period highlights the persistence of this issue on a global scale (WOAH, 2024). At the same time, antimicrobial resistance (AMR) continues to represent one of the major global health threats, with recent estimates indicating approximately 4.95 million deaths associated with drug-resistant infections in 2019, of which 1.27 million were directly attributable to AMR (Antimicrobial Resistance Collaborators, The Lancet, 2022). In this context, the environment is increasingly recognised not only as the final sink for contaminants, but also as a potential reservoir and amplifier of the selective pressure that favours the emergence and spread of resistant microorganisms.

Antibiotics are used in human medicine, livestock production, aquaculture and, in some settings, agriculture. Following administration, a substantial proportion of these molecules is excreted unchanged or as metabolites and may reach aquatic environments through municipal, hospital, livestock and industrial wastewater. Wastewater treatment plants do not always ensure the complete removal of these compounds, thereby facilitating their release into surface water bodies and, in some cases, groundwater. This phenomenon is of primary importance for public health, as it lies at the interface between antimicrobial use in the environmental, animal and human sectors and the food chain, favouring the emergence and spread of antimicrobial resistance. Its complexity therefore requires an integrated interpretation, able to consider human health, animal health and the environment together, in accordance with the One Health approach.


Regulatory framework and environmental monitoring

In a global context that remains far from uniform, the monitoring of emerging contaminants, including PPCPs in water, finds in the European Union one of the few examples of a structured regulatory system. The overarching framework is provided by the Water Framework Directive 2000/60/EC, which introduced the principle of good ecological and chemical status for surface waters, groundwater, inland waters and transitional waters, requiring Member States to adopt monitoring programmes and pollution reduction measures.

For surface waters, the European regulatory framework was further strengthened by Directive 2013/39/EU, which introduced, among other provisions, the Watch List mechanism. This surveillance tool was designed to collect harmonised monitoring data at European Union level on emerging contaminants that may be relevant to aquatic ecosystems and human health, but for which the available knowledge is not yet sufficient to define legally binding environmental quality standards.

Substances included in the Watch List are monitored by Member States for a limited period of time, according to shared criteria, in order to obtain comparable data on their occurrence and distribution in the environment. The information collected provides the scientific basis for assessing the possible inclusion of these substances in the list of priority substances and the subsequent adoption of more stringent regulatory measures.

The European Watch List is a periodically updated list of emerging substances to be monitored in surface waters across the European Union. Its purpose is not to introduce immediately binding regulatory limits, but rather to collect harmonised and comparable data among Member States on substances that may pose a risk to the environment or to human health.

In this sense, the Watch List represents a preparatory tool that allows contaminants of potential concern to be identified at an early stage and their environmental distribution to be assessed. The evidence generated through monitoring supports subsequent regulatory decisions, including the possible inclusion of these substances among those subject to stricter control measures.

 

A further qualifying element of the European system is the requirement for analytical methods with very low detection limits, often in the ng/L range, which are essential for detecting diffuse contamination occurring at low concentrations.

Outside the European Union, the approach to PPCP monitoring is more fragmented. In several countries, including the United States and China, these substances are not yet fully integrated into regulatory water-monitoring programmes, contributing to substantial heterogeneity in the availability of environmental data.



Antibiotics in surface water and groundwater: where they are found and what we know

From the perspective of the geographical distribution of available data, Europe, Asia and the Americas are the most extensively investigated areas, whereas Africa and Oceania show a significant lack of information, highlighting marked disparities in knowledge at global level. At the same time, there is growing interest in remote environments, such as Antarctica, which are regarded as sentinel systems for studying diffuse contamination and assessing the global dissemination of resistance determinants.

The environmental matrices most frequently investigated are surface waters, particularly river systems, followed by marine and lake environments. Groundwater, by contrast, is less represented in monitoring programmes, probably also because of the limited availability of dedicated mapping and sampling networks (Jasechko et al., 2024).

With regard to the antibiotic classes most frequently investigated and detected, the literature shows a predominance of sulfonamides, macrolides, quinolones, diaminopyrimidines and tetracyclines. By contrast, pleuromutilins, rifamycins, sulfones and aminoglycosides are poorly studied and rarely detected. Particularly relevant is the almost complete lack of data on polymyxins and carbapenems, despite their extensive use in human and veterinary medicine. These gaps may be attributed both to the absence of surveillance programmes targeting these molecules and to the analytical difficulties faced by laboratories responsible for monitoring.

Among individual substances, sulfamethoxazole is the antibiotic most frequently detected internationally. Its widespread use in human and veterinary medicine, often in combination with trimethoprim to increase therapeutic efficacy, probably contributes to its widespread occurrence in water. Azithromycin, which belongs to the macrolide class, has also been frequently detected in environmental monitoring; this finding may be related to the significant increase in its use during the COVID-19 pandemic (do Nascimento et al., 2026).

Ciprofloxacin, one of the most widely used antibiotics worldwide for the treatment of urinary and respiratory tract infections, and tetracycline are also of considerable importance. Both molecules are regarded as priority contaminants in studies on antimicrobial resistance, owing to their frequent occurrence in the environment and their association with processes of selection and maintenance of resistant bacteria (EFSA and ECDC, 2026). Figure 1 summarises the detection frequency of the antibiotics most commonly reported in the scientific literature between 2014 and 2024 (Rosato et al., 2025).

Figure 1. Most frequently detected antibiotics (number of observations ≥30) in surface water and groundwater worldwide between 2014 and 2024


Environmental fate of antibiotics and transformation products

Environmental assessment of antibiotics often focuses on the parent compound, although a substantial proportion of contamination may be associated with transformation products (TPs), generated both through metabolic processes in organisms and during wastewater treatment. Conventional wastewater treatment plants do not guarantee the complete removal of antimicrobial residues and, in some cases, may create conditions favouring the transformation of the original molecules into other chemical forms.

Once released into the environment, antibiotics may undergo physical, chemical and biological processes, including adsorption, migration and degradation. The resulting transformation products may exhibit adverse effects similar to those of the parent molecules and exert toxic effects on plants and animals, thereby posing a risk to ecosystem stability. They may also contribute indirectly to selective pressure on environmental microorganisms by inhibiting the growth and activity of some species while favouring others, thus supporting the spread of antimicrobial resistance.

Antibiotics may undergo several transformation and degradation processes in the environment, both abiotic and microbial in nature. The main mechanisms include:

  • Hydrolysis: compounds such as beta-lactams, amphenicols and macrolides, which are characterised by good water solubility, are frequently susceptible to hydrolysis reactions once released into the aquatic environment.
  • Photolysis: antibiotics may undergo photolysis in surface waters or when bound to sediment. Direct photodegradation involves the cleavage of chemical bonds through electronic transitions activated by ultraviolet and visible radiation. Literature data have shown that molecules such as sulfamethoxazole and sulfadiazine have a high tendency to undergo photodegradation; consequently, concentrations detected during environmental monitoring may not fully reflect their actual environmental occurrence, because of the rapid transformation of these compounds. Indirect photodegradation is mediated by natural photosensitisers, such as humic substances and algal organic matter, which absorb light energy and generate reactive oxygen species and free radicals that can react with antibiotic molecules, accelerating their transformation.
  • Biological transformation: in activated sludge wastewater treatment plants, microorganisms contribute to the transformation of antibiotics through enzymatic reactions, including N-oxidation processes, for example for quinolones and sulfonamides, and the hydrolysis of macrolide rings.

The migration and transformation of compounds in the environment are also strongly influenced by environmental factors, such as temperature, water mobility, pH and light intensity (Zhang et al., 2025).

Current knowledge on the occurrence and degree of risk to human health posed by TPs remains limited and derives mainly from studies conducted in Europe. This represents an important critical issue, because TPs are often excluded from routine surveillance activities, despite their potential to contribute significantly to ecotoxicological risk and to the selection of resistance.

Löffler et al., in a study published in 2023, estimated the risk of AMR development associated with 32 TPs belonging to different antibiotic classes, including lincosamides, macrolides, nitroimidazoles, penicillins, sulfonamides and tetracyclines. The assessment, based on concentrations detected in surface waters and reported in studies published between 2002 and 2021, showed that in many cases the estimated risk levels for transformation products were comparable to those of their respective parent compounds. For some TPs of tetracycline and metronidazole, the estimated risk was even higher than that of the parent compound, whereas the opposite trend was observed for amoxicillin, whose transformation products were characterised by a lower risk than the original molecule.

A relevant limitation of the study concerns the absence of specific PNEC-AMR values (Predicted No-Effect Concentration for Antimicrobial Resistance) for transformation products. This parameter represents the concentration below which the onset of significant selective pressure capable of favouring the emergence or maintenance of antimicrobial resistance is not considered likely. In the absence of such values, the risk assessment was carried out using indirect approaches based on the structural similarity between the transformation product and the corresponding parent compound.



Future perspectives and conclusions

Antimicrobial resistance is a complex and multidimensional phenomenon, in which the environmental compartment plays an increasingly recognised role, not only as the final sink for contaminants, but also as a possible element in the maintenance and dissemination of selective pressure.

In this context, monitoring antibiotic residues and their related transformation products in aquatic matrices is an essential tool for improving understanding of exposure pathways and for identifying potentially critical environmental areas and conditions. The integration of environmental data with clinical and veterinary data represents a key step towards a more comprehensive assessment of the risk associated with AMR.

Current evidence, however, shows marked heterogeneity in surveillance strategies, both geographically and methodologically, limiting data comparability and the development of reliable global scenarios. This is compounded by the need to broaden the field of observation beyond parent compounds alone, by systematically including transformation products, which remain poorly characterised.

Strengthening environmental monitoring programmes, harmonising analytical protocols and developing shared indicators are therefore priority elements for improving the ability to detect early warning signs of risk and to support more effective mitigation policies. Ultimately, an integrated approach consistent with the One Health perspective is essential to address the challenge of antimicrobial resistance in a structural manner, reducing scientific uncertainty and strengthening strategies to protect aquatic ecosystems and public health.



References

  1. WOAH (World Organization for Animal Health), 2023. Annual report on antimicrobial agents intended for use in animals-7th report

  2. WOAH (World Organization for Animal Health), 2024. Annual report on antimicrobial agents intended for use in animals-8
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  3. Antimicrobial Resistance Collaborators, 2022. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet 399 (10325), 629-655

  4. Jasechko, S., Seybold, H., Perrone, D., Fan, Y., Shamsuddhua, M., Taylor, R.G., Fallatah, O., Kirchner, J.W. “Rapid groundwater decline and some case of recovery in aquifers globally” Nature 625, 715-721, 2024

  5. Birelli do Nascimento, B., Belline Silva, B.G., Aparecido de Souza, L., Bilizario Nogueirol Andrade, J.C., de Sá Del Fiol, F. “From Widespread Use to Loss Effectiveness: The Consequences of Inappropriate Azithromycin Prescriptions During the COVID-19 Pandemic - A Systematic Review and Meta-Analysis” International Journal of Microbiology 8643896, 1-8, 2026

  6. EFSA (European Food Safety Authority), ECDC (European Centre for Disease Prevention), 2026. The European Union Summary Report on Antimicrobial Resistance in zoonotic and indicator bacteria from humans, animals and food in 2023–2024. EFSA Journal 2026; 24:e9887

  7. Rosato, R., Castellani, F., Ricci, M., Manucci, A., Di Simone, V., Scortichini, G., Saluti, G. “Antibiotics in the aquatic environment. A deep voyage across chemical occurence data, socio-economic relationships and international policies on antimicrobial consumption and resistance within 2014-2024” Science of the Total Environment 1002, 180543, 2025

  8. Zhang, Y., Jiang, J., Feng, M., Ye, C. “Transformation products of antibiotics: overlooked drivers for enhancing the environmental spread of antibiotic resistance” Journal of Environmental Exposure Assessment 4, 10, 2025

  9. Löffler, P., Escher B.I., Baduel, C., Virta, M.P., Yin Lai, F. “Antimicrobial Transformation Products in the Aquatic Environment: Global Occurence, Ecotoxicologiacl Risks, and Potential of Antibiotic Resistance” Environmental Science & Technology 57, 9474-9494, 2023.

Giorgio Saluti
Istituto Zooprofilattico Sperimentale dell’Abruzzo e del Molise “G. Caporale”, Department of Food Chemistry and Veterinary Drug Residues

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