Case study: Tetracycline antibiotics in the environment

Antibiotic medicines have been an important development for human health, and they’re credited with improving the average human lifespan. While important for human and animal health, there are issues from the overuse of these medicines, including antimicrobial resistance and possible environmental harms.

The Parliamentary Commissioner for the Environment's report Knowing what’s out there: Regulating the environmental fate of chemicals is an analysis of how New Zealand regulates chemicals, including antibiotics, and how these chemical compounds enter and affect our environment. The report has case studies of a selection of chemicals that look at the life cycle of the substance, which includes its manufacturing, import, use, transport, disposal environmental fate. The case studies are intended as examples of the different ways the environmental fate of chemicals are managed by New Zealand’s regulatory system.

Four chemicals were selected for this purpose, one of which was the antibiotic group, tetracyclines.

Tetracyclines

Antibiotics are a set of drugs used to treat infection caused by bacteria and some other microorganisms. An antibiotic will either kill bacteria or impede the growth or reproduction of the bacteria to stop the spread of the infection. This is referred to as their mechanism (or mode) of action. For example penicillin kills bacteria by destroying the bacterial cell wall.

Tetracyclines are a class of broad-spectrum antibiotics including doxycycline and oxytetracycline. Tetracyclines are designed to inhibit protein synthesis in bacterial cells – this means they kill bacteria by preventing them from producing essential proteins, impairing cell growth and reproduction.

Tetracyclines are some of the most frequently used antibiotics because they act against a wide range of bacteria and are not very expensive. They’re used to treat human and animal infections in the skin, chest, urinary tract, genitals and lymph nodes. They are used in combination with other medications to treat stomach ulcers and as a preventative for malaria. In New Zealand, tetracyclines are mainly used in farmed animals (pigs, chickens, sheep and cows) with smaller amounts used for companion animals like cats and dogs and aviary birds.

The chemistry of tetracyclines

Tetracyclines can readily dissolve in water and are often not fully metabolised by the body. On average, more than 75% of tetracyclines consumed by humans and livestock are released into the environment in an active form (either as the main compound or as a metabolite) via:

• faeces and urine
• the spread of manure and biosolids
• treatment plant effluents.

Tetracyclines have an affinity for sticking to the surface of soil (especially to acidic and clay soils), sludge, manure and sediments. When they are bound to these types of soils, it means they are less likely to leach into surface water or groundwater or be taken up by non-target organisms. The stronger the bonds between soils and tetracyclines, the lower the uptake by organisms and the slower the degradation. This suggests that strong bonds may increase the time the antibiotic is active in the environment.

Once in the environment, ultraviolet light and microbial activity break down tetracyclines. In soils, the breakdown of tetracyclines is further influenced by the presence of specific metal ions, type of soil and pH. Fo example, the presence of magnesium and manganese oxides slow down the degradation process, while calcium or ferric (Fe³+) ions speeds it up.

Tetracyclines in the environment

Worldwide, tetracyclines are the second most frequently detected subclass of antibiotics in the environment. Tetracyclines and their metabolites have been found in low concentrations in above 80% of samples from environments surveyed overseas. Likely reasons for this high detection rate include repeated use of manure from livestock (who have been given tetracyclines) as a fertiliser and the long time it takes for tetracyclines to break down in soil. The strong adsorption and the slow degradation of tetracycline results in its persistence in topsoil, leading to potentially higher environmental risks to microorganisms..

Usually when faced with a lack of New Zealand-specific data, scientists will look to overseas research. However, there is no systematic reporting for the amount of tetracycline antibiotics imported into New Zealand, so we can’t compare it to international levels.

Environmental concentrations of tetracyclines below the detection limits of analytical tools have been found to trigger antimicrobial resistance in some regions of Europe, Asia and North America.

Toxicity

Tetracyclines can have negative effects on non-target species (i.e. not the bacteria they are intended to kill) such as algae and invertebrates. When compared to other antibiotics, tetracyclines are most toxic to beneficial to bacteria in the to soil, freshwater fleas and aquatic algae. While the toxicity of tetracycline compounds may be higher than that of other antibiotics, their availability and mobility to different systems is limited because of their affinity to soils, sediments and sludge.

Key environmental concerns

The toxicity of breakdown products (or metabolites) of tetracycline has yet to be fully assessed. While recent research has focused on the impact of tetracyclines on different organisms, there is a need to focus on the environmental risks associated with low exposure concentrations of both the antibiotic and it’s breakdown products.

To date, there are no accepted international guidelines, environmental limits or antibiotic reference standards for antibiotic pollution. This affects the way they are monitored and addressed in receiving environments.

The lack of monitoring of tetracyclines and tetracycline-resistant genes in the environment hinders our ability to assess their transport pathways, their interactions with other chemicals, and the potential risk for antimicrobial resistance development.

Knowing what’s out there: Regulating the environmental fate of chemicals

Report case study findings

These are some of the findings of the report case study on tetracyclines:

• There is some concern over the use of tetracyclines (and other antibiotics) in both humans and animals may trigger antimicrobial resistance in bacteria. There is a lack of regulation to monitor and treat tetracyclines at wastewater treatment plants or in manure as fertiliser in farmlands.
• Guidance is lacking for the disposal of antibiotic-containing vials that may contain residuals of the antibiotics. Currently, unused and empty containers are generally sent to landfill.
• The absence of monitoring programmes for antibiotics in different environments limits our ability to determine the risks they may pose to receiving environments.

How would you find solutions/solve some of the issues from the report findings? How might your approach differ if you were a scientist, a politician, a farmer, or a student at secondary school?

New Zealand’s current surveillance and the national antibiotic strategy

Some data on human and animal antibiotic consumption is collected via the Ministry of Health and through the Ministry of Primary Industry’s survey of use for animals. This valuable dataset helps identify volumes dispensed, general use patterns and the effectiveness of treatment.

The report Knowing what’s out there: Regulating the environmental fate of chemicals, stated that information collected through surveillance is fundamental for progressing the 2017 New Zealand Antimicrobial Resistance Action Plan – a strategy focused on addressing antimicrobial resistance.

In late 2021, the Office of the Prime Minister’s Chief Science Advisor (OPMCSA) produced the report Kotahitanga: Uniting Aotearoa against infectious disease and antimicrobial resistance, which notes “almost none of the recommendations made in the 2017 action plan have been put into place”. This report echoes the Parliamentary Commissioner for the Environment, stating, “We lack an understanding of the amount and distribution of antimicrobials in the environment in Aotearoa New Zealand, and we don't know what impact they have on the development of AMR [antimicrobial resistance], nor the potential flow-on impacts for human, animal, and plant health.”