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Antibiotics in the environment

Before we started using antibiotics as medicines, antibiotic resistance in human and animal pathogens was not common. Today, multidrug-resistant bacteria are a major threat to our health. So then, from where do these resistant and multidrug-resistant bacteria emerge?

Selection of resistance in bacteria in the body during antibiotic treatment is one important source, especially in health care facilities where antibiotic use is high. More and more scientific evidence also suggests that antibiotic resistance genes and antibiotics in the environment play an important role both in the emergence and spread of resistance (reviewed in). All resistance genes in the environment can be regarded as a big “pool” of resistance genes (a “resistome”) that can potentially transfer to pathogenic bacteria.

Sources of environmental pollution

Waste from large-scale animal farms, use in aquaculture and wastewater from antibiotic manufacturing, hospitals and municipalities are major sources of antibiotic resistance genes and antibiotic pollution in the environment. Parts of the antibiotics given to humans and animals are excreted unaltered in feces and urine. In the case of waste from animals, manure is rich in nutrients and is often used as fertilizer on crop fields, leading to direct contamination of the environment with both antibiotic residues and resistant bacteria.

Two potential threats to human health

There are two potential distinct threats where environmental contamination with antibiotics and antibiotic resistance elements can have severe consequences for human health (not considering potential direct toxic effects):

  1. Spread of resistant bacteria or resistance genes
  2. Emergence of new resistance in pathogenic bacteria

There have been reports on antibiotics and antibiotic resistant bacteria found in river water and sediments. As just one example, urban river water samples in Baltimore contained more pharmaceutics, including antibiotics, than suburban samples. The presence of antibiotics in the water also affected the microbial communities in the rivers..

Antibiotics and resistance common in some environments

Example: Animal farming

A study at three high-production pig farms in China found increased concentrations of antibiotics in the manure and soil at the farms, and three times as many unique resistance genes as compared to in control manure/soil. The authors estimated that the most abundant resistance gene on average would be found in nearly every second bacteria in that setting. In addition, mechanisms that allow spread of resistance genes between bacteria were also common.

Example: Pollution from antibiotic manufacturers

Concentrations of antibiotics in effluents from antibiotic-manufacturing sites can reach extremely high levels. At one wastewater plant in India, which is receiving waste from ~90 drug manufacturers, 45 kg (99 lbs.) of ciprofloxacin were released into the nearby river each day. As a comparison, the total daily consumption for the whole country of Sweden, is 9 kg. Apart from the obvious risks of toxic effects on living organisms of such antibiotic concentrations, it was observed that resistance genes were enriched in river sediments.

As antibiotics are transported with water and through the sediments and soil, gradients of different antibiotic concentrations will form. Even very low antibiotic concentrations may be enough to select for highly resistant bacteria, and has been demonstrated to do so at least in the laboratory.

Will resistance spread to pathogenic bacteria?

The probability that resistance genes in environmental bacteria are transferred to and maintained by pathogenic bacteria may be low. However, if this happens, it will have major consequences. Also, as the types and abundance of antibiotic resistance genes in the environment increases, and the time they stay there, so does the risk that it will happen. Wastewater treatment plants may contribute in this process, as it is a place where bacteria from the environment meet human pathogenic bacteria as well as bacteria that are part of our normal human flora without causing disease. Multidrug-resistant bacteria have been detected in high numbers in treatment plants.

Another study has provided evidence that certain resistance genes from soil bacteria share similarities with resistance genes in bacteria that are infecting humans. This indicates that soil bacteria can be a direct source of resistance for pathogenic bacteria.

Resistant bacteria and antibiotics in the environment have severe consequences

The accumulation of antibiotic resistant bacteria and antibiotics in the environment can have severe consequences. Humans may become directly sick or colonized by antibiotic resistant bacteria when consuming contaminated food or water or through direct contact with animals. In addition, antibiotics also provide a selection pressure for environmental bacteria to maintain antibiotic resistance mechanisms. They may also increase the risk that novel resistant pathogenic bacteria arise and spread. It is crucial to understand that it is all use of antibiotics, whether appropriate or not, that is the cause of increased prevalence and rapid spread of antibiotic resistance as well as the emergence of new, multidrug-resistant pathogens that are threatening our entire health system.

Selected Resources

Resource Description
The costs and risks of AMR water pollution This paper provides an overview of the relationship between antimicrobial resistance (AMR) and water pollution. It explores the underlying causes of waterborne AMR, together with the risks and economic consequences of inaction. This briefing paper summarizes the 2020 technical report.
TEDxUniversityofGothenburg: Our Drugs in their Water Video. TEDx talk by Joakim Larsson about the role of antibiotic pollution in external environment in the selection of antibiotic resistance and subsequent gene transfer to the human microbiome (15 min).
Water reuse management: Is pharmaceutical pollution a real problem? Factsheet from Health Care Without Harm describing the environmental risks and effects of pharmaceutical contamination of wastewater.

More from "How did we end up here?"

1.
Joakim Larsson. Our Drugs in their Water. https://www.youtube.com/watch?v=_XclE3LeVmo (2011).
1.
World Economic Forum. The costs and risks of AMR water pollution. https://www.weforum.org/reports/the-costs-and-risks-of-amr-water-pollution/.
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Health Care Without Harm. Water reuse management: Is pharmaceutical pollution a real problem? Preprint at https://noharm-europe.org/documents/water-reuse-management-pharmaceutical-pollution-real-problem.
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Forsberg, K. J. et al. The shared antibiotic resistome of soil bacteria and human pathogens. Science 337, 1107–1111 (2012).
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Rosi, E. J. et al. Urban stream microbial communities show resistance to pharmaceutical exposure. Ecosphere 9, e02041 (2018).
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Wistrand-Yuen, E. et al. Evolution of high-level resistance during low-level antibiotic exposure. Nature Communications 9, 1599 (2018).
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Finley, R. L. et al. The scourge of antibiotic resistance: the important role of the environment. Clin. Infect. Dis. 57, 704–710 (2013).
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Larsson, D. G. J., de Pedro, C. & Paxeus, N. Effluent from drug manufactures contains extremely high levels of pharmaceuticals. J. Hazard. Mater. 148, 751–755 (2007).
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Gullberg, E. et al. Selection of resistant bacteria at very low antibiotic concentrations. PLoS Pathog. 7, e1002158 (2011).
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Kristiansson, E. et al. Pyrosequencing of antibiotic-contaminated river sediments reveals high levels of resistance and gene transfer elements. PLoS ONE 6, e17038 (2011).
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Marathe, N. P. et al. A treatment plant receiving waste water from multiple bulk drug manufacturers is a reservoir for highly multi-drug resistant integron-bearing bacteria. PLoS ONE 8, e77310 (2013).
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Perry, J. A. & Wright, G. D. The antibiotic resistance ‘mobilome’: searching for the link between environment and clinic. Front Microbiol 4, 138 (2013).
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Zhu, Y.-G. et al. Diverse and abundant antibiotic resistance genes in Chinese swine farms. Proc. Natl. Acad. Sci. U.S.A. 110, 3435–3440 (2013).
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Perry, J. A., Westman, E. L. & Wright, G. D. The antibiotic resistome: what’s new? Curr. Opin. Microbiol. 21, 45–50 (2014).