Wastewater As a Key Driver of AMR

Environmental discharge of wastewater.
Source: U.S. Department of Agriculture. Wastewater—used water resulting from rainwater runoff and human activities—serves as a dynamic vehicle for the spread of antimicrobial resistant microbes, antimicrobial drug residues and antimicrobial resistance (AMR) genes in the environment. High concentrations of AMR genes and AMR organisms have been detected in environmental samples recovered from hospital and urban-treated wastewaters.

The spread of AMR in the environment represents an immense threat to the survival of living organisms, including humans. This is, in part, because antimicrobial drug residues have ecotoxicological effects on the environment, thereby contributing to loss of microbial diversity, pollution and waste generation. Consequently, AMR has been recognized by the United Nations General Assembly and the World Health Organization (WHO) as a global threat requiring urgent attention. This calls for pragmatic measures to be taken against this menace through the implementation of sustainable interventions.

How Does Wastewater Contribute to AMR?

Wastewater is typically categorized based on the way it is produced (e.g., domestic, industrial, hospital or rainwater runoff). It is a common feature among 5 main pollutant sources that play a major role in the emergence, transmission and dispersal of AMR in the environment.

1. Sewage: Antimicrobial drug residues excreted in feces are released in the environment through improper waste disposal, inadequate wastewater management and poor sanitation. These minimal doses of antimicrobials exert selective pressures on microbial communities in domestic and industrial drainage systems, rivers, seawater and the soil. Consequently, sewage and effluent (liquid waste) from septic tanks, as well as sewage treatment plants, have been found to contribute significantly to AMR pollution in the environment.
    
2. Pharmaceutical ingredients: Pharmaceutical companies contribute to effluent and produce waste that can contain active pharmaceutical ingredients. These active ingredients have been detected in the environment at concentrations that could potentially increase the abundance of resistant microbes and AMR genes.
    
3. Health care facilities: Effluent and waste from health care facilities can contain concentrations of AMR genes and microbes up to 10 times higher than wastewater from surrounding communities.
    
4. Crop treatment: The use of antibiotics and fungicides—as well as manure resulting from inadequately treated or untreated wastewater—in crop production could introduce antimicrobial drug residues and resistant microbes into the environment. Additionally, the use of soil fertilizers resulting from dried, digested, activated sludge may cause antibiotic contamination in surface runoff, groundwater and drainage networks.
    
5. Livestock farming: In a quest to ensure livestock health and productivity, intensive terrestrial and aquatic animal production systems often use antimicrobial drugs. Yet, the wrongful use of antimicrobial drugs in animal husbandry for growth promotion and disease prevention, instead of the recommended sole use in the treatment of infected animals, greatly contributes to the rapid emergence of AMR. A high percentage of these antimicrobial drugs are excreted through urine and feces, which are subsequently released into the environment either directly or indirectly through wastewater.

The Spread of AMR in Wastewater: Why Is it Concerning?

As a result of human activities, coupled with poor sanitation, sub-therapeutic doses of antimicrobial drugs and disinfectants accumulate in the environment over time. Even though the concentrations of antimicrobial drugs in effluent is too low to be lethal to the exposed microbes, it may be enough to promote the emergence and spread (via vertical or horizontal gene transfer) of microbes with mutations that confer resistance to the corresponding drugs.

While vertical gene transfer occurs when genes are passed from 1 generation to another, horizontal gene transfer facilitates the acquisition of AMR genes by non-resistant microbes from other microbes that are not necessarily genetically related. The resulting resistant microbes may then be transmitted to (and between) humans and animals. For example, human exposure to AMR from the environment can take place following consumption of food and/or water that have become contaminated by resistant microorganisms and can lead to human infections.

The development of AMR.
Source: ASM.The introduction of antimicrobial drugs to the environment via disposal practices that contaminate waterbodies and soil varies from country to country. In countries with developed sewer networks, antibiotics used in clinical settings and large-scale farms end up in collected wastewater, which is treated before being discharged into the environment.

However, even though conventional methods of wastewater treatment kill live microbes, they usually do not eliminate antimicrobial drug residues or pieces of environmental DNA, including AMR genes. Rather, following treatment, most antimicrobial drugs are reduced to their individual molecular units via hydrolysis. This is usually observed for residues of commonly used antibiotics, like beta-lactams, sulphonamides, tetracyclines and quinolones. These individual molecular units accumulate over time in the environment, thereby increasing the exposure of environmental microbes to these traces and contributing to the emergence of AMR.

Inadequate treatment of wastewater exacerbates the spread of AMR. In many under-resourced countries, less than 10% of wastewater is adequately treated. In fact, on a global scale, over 56% of domestic and industrial wastewater is released into the environment with little or no treatment. Furthermore, untreated or inadequately treated wastewater is a potential source of toxic compounds and can contain high levels of nutrients, like phosphorus and nitrogen, which can cause eutrophication. The health of freshwater and marine organisms is also at risk if direct or indirect discharge of untreated wastewater makes its way into streams and oceans. Yet, untreated or inadequately treated wastewater is often used for irrigation purposes and greatly contributes to water and food security in developing countries.

Considering the complex composition of wastewater, and the need to safeguard aquatic ecosystems, it becomes important that wastewater is treated before it is released into the environment. When wastewater management is enhanced, the health of agricultural workers will be improved, as the risk of pathogen exposure and chemical contaminants will also be reduced.

How Can the Environmental Spread of AMR Be Curbed Sustainably?

 The spread of AMR in the environment.
Source: UNEP, 2020. Millions of lives across the globe will be at risk from AMR by 2050. The One Health approach, which is a collaborative strategy encompassing environmental, animal and human health, is crucial to curtail the rise in the emergence of AMR. Everyone in society has an important role to play in ensuring that AMR is combated in a sustainable manner. 

Deliberate efforts to ensure that antimicrobial drugs are used responsibly, can reduce the concentration of antimicrobial drugs that end up in wastewater in the first place. Still, given the global status of AMR, further action is needed. The removal of pathogenic microbes—as well as drug residues and AMR genes—must be a focus in the treatment of wastewater.

With that in mind, although the removal of AMR genes from wastewater can be achieved using various methods including biological, chemical, physicochemical and physical treatment processes, it is usually not incorporated into routine conventional wastewater treatment.

What's Next? Applications in AMR Gene Removal

Given that conventional wastewater treatment methods are essential but ineffective against the complete removal of AMR genes, innovative, cost-effective and environmentally friendly techniques are being developed. One such intervention is based on the adsorption for nucleic acids during wastewater treatment. Adsorption is a separation method whereby total environmental DNA, including AMR genes and mobile genetic elements, fuse iron oxide-coated sand and are removed from treated wastewater.

There are various nucleic acid-adsorbing materials that have been studied and applied to target AMR reduction from wastewater, including bio-based adsorbents like biochar (the lightweight black product resulting from the burning of any organic matter, including sewage sludge), iron oxide-coated reclaimed sand and modified eggshells. For example, iron oxide-coated sand and sewage sludge biochar were respectively reported to retain 54%-85% of antibiotic resistant genes, mobile genetic elements and free-floating extracellular DNA from wastewater. In other studies, high adsorption capacity and inhibition of AMR genes has also been reported for non-biobased adsorbents, such as graphene oxides and ceric oxide (CeO2).

Despite the promising nature of these methods in the removal of antimicrobial resistant genes from wastewater, a number of critical factors including material toxicity, cost-effectiveness, affordability, leaching property and scalability have been identified that are worthy of consideration. Consequently, the search for biological and cost-effective materials that would efficiently remove AMR genes from wastewater continues.

Learn More About How Microbes Help Us Reclaim Our Wastewater

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In This Issue:

• Lessons From a Decade of Antimicrobial Resistance Policy
• Growing Resistance: How Plant Agriculture Contributes to AMR
• Understanding the Risks of Antifungal Resistance
• Experts in East Africa Propose Equitable AMR Interventions
• Wastewater As a Key Driver of AMR
• Exploring a One Health Approach to AMR in Pakistan
• Federally Qualified Health Centers Lead AMR Stewardship
• Updating Breakpoints in Antimicrobial Susceptibility Testing
• Hunting for Antibiotics in Unusual and Unculturable Microbes
• What's Hot in the Microbial Sciences