Growing Resistance of Antibiotics
One of the miracles of modern public health systems is the wastewater treatment facility, providing clean, drinkable water to millions. Moreover, it offers a line of defense against antibiotic-resistant bacteria. But questions have arisen over these treatment plants because of the on-site intermixing of antibiotics and bacteria. Antibiotics have been greatly accumulating in wastewater in recent decades, and vast growths of bacteria are used in treatment facilities to break down toxins.
Antibiotic failure due to increasing antibiotic resistance has become a worldwide threat to public health. The US Centers for Disease Control and Prevention (CDC) has reported a rapid rise in cases of antibiotic-resistant bacterial infections. In 2013, the US alone suffered two million cases, with twenty-three thousand deaths[1]. By 2019, these cases had jumped to 2.8 million, with thirty-five thousand deaths. Globally, antibiotic resistance accounts for at least seven hundred thousand lives lost per year[2].
Over time, the world sees more and more antibiotic resistance to the important antibiotics that humanity has used to protect ourselves for the last seventy or eighty years. The World Health Organization (WHO) has documented what it calls priority pathogens, including Staphylococcus aureus, which display significant resistance to multiple antibiotics. These antibiotic-resistant bacteria (ARBs) and antibiotic resistance genes (ARGs) can lead to deadly infections and increase the risk of complications during medical procedures.
A major cause of this growing resistance is the widespread use and even overuse of common antibiotics. The CDC reports that as much as 30% of the roughly 250 million antibiotic prescriptions filled annually are unnecessary.
Antibiotics are also used extensively in animal food production. The most common antibiotic used in animal agriculture is tetracycline. Farmers feed cows and pigs plenty of tetracycline to keep them healthy while raising them under adverse conditions, such as severe overcrowding.
Since 2009, the US Food and Drug Administration (FDA) has tracked how much of each antibiotic considered important for the protection of human health is sold for animal agriculture. The overall amount sold increased annually from 2009 to 2015, when totals peaked at 9.7 million kg (21.6 million lbs). Recognizing the need to curb overuse, the FDA has since worked to reduce these amounts. The agency’s latest report, published in December 2020, shows improvements, with an overall sales drop to roughly 6.2 million kg (13.6 million lbs), a 36% decrease from 2015 to 2019 (but including a 3 percent increase from 2018). It remains to be seen if this decrease is a temporary fluctuation or a sign of a long-term positive trend.
Wastewater Treatment and Antibiotic Resistance
ARBs and ARGs can be spread throughout the environment by a number of means. These include wind, soil and water movement, and animal vectors. One emerging area of research is the transport of ARBs and ARGs in water, especially wastewater.
Antibiotics are used far and wide for human health, in agriculture, and in other places. Eventually, they collect in wastewater treatment plants. Antibiotics do not linger in our bodies. Whether consumed as medicine or through our food, antibiotics are eventually expelled and wind up in wastewater. And when antibiotics are manufactured, the wastewater produced is also sent to treatment plants. Once treated, this water may eventually be discharged to ground surfaces, where it can enter aquifers and the drinking water supply. Alternatively, processed wastewater can be used to irrigate and grow the plants we eat.
Thus, a key question arises: Are wastewater treatment plants protecting the environment and human health from the spread of antibiotic resistance?
There is a concern around potential ARG production in treatment plants based on the way treatment plants work. Such facilities harness natural processes, including the action of bacteria and protozoa, to clean and filter toxins from the water that comes in. Wastewater plants develop bacteria that are able to break down and detoxify the types of contaminants typical for the local community. These can be industrial chemicals, organic materials, domestic cleaning compounds, and the like. Once they adapt, these bacteria thrive in the plant’s environment, increasing their numbers while acting as an important partner in reducing pollution.
Treatment plants both develop these specialized strains of useful bacteria and reduce the presence of bacterial, viral, and protozoan pathogens. It is common for a treatment plant to reduce harmful pathogens by 99% or more. Follow-on processes, including the use of chlorine compounds or ultraviolet treatments, provide additional disinfection that can result in pathogen reduction of 99.99% or more.
Understanding the process begs the question: Can these plants that are designed to grow toxin-digesting bacteria also grow bacteria that adapt to metabolize or resist antibiotics present in wastewater?
It is critical to ensure that wastewater treatment plants are neither creating more ARBs nor releasing ARGs from the plants back into circulation.
To this end, my research team at the University of California, Los Angeles, reviewed studies from around the world on the presence of ARGs in wastewater treatment facilities. From twenty-five studies containing 215 observations of various treatment processes, including activated sludge and membrane bioreactors, we found that 70% of observations showed ARGs decreased, 18% showed increases, and 12% indicated no changes.
However, we observed some issues with the available data. Since much of the previous research was conducted with other goals in mind, the data did not always reflect the key measurements we were investigating. Furthermore, in some cases, the details identifying the various types of wastewater treatment plants were not always reported accurately. This was likely because much of the research was conducted by molecular biologists and scientists in other specialties, rather than wastewater treatment plant experts. Therefore, the final reported percentages (70, 18, and 12) may not be accurate either.
Plants are constructed in different ways and have different operating strategies. These differences in design and strategy greatly affect the performance of the plant for removing specific pollutants. For example, a facility treating the heavy toxins in petroleum refinery wastewaters must be designed and operated differently than a plant handling wastewater from potato processing.
My team is currently embarking on an extended research project to track ARGs through modern, well-operated treatment systems. We need to understand the fate of ARGs that enter wastewater treatment plants and are potentially released into the environment. Our goal is to determine if these quantities are increasing and, if so, how to stop this.
We recently completed preliminary research on the fate of ARGs in a selection of treatment plants in southern California that utilize the activated sludge process. Activated sludge is the most common approach used for treatment and is especially useful in large cities and densely populated areas. We targeted plants that were representative of the majority of municipal treatment facilities where antibiotics are found. These plants serve hundreds of thousands of people and include hospitals, with their specialized wastewaters.
The plants were selected in pairs to identify the most important operating characteristic, the solids retention time (SRT), also called mean cell retention time or sludge age. The SRT is the average age of the bacterial cells harnessed to treat waste. The measure can range from 1.5 days (short SRT) to 30 days (long SRT). This identification is critical, because slowly growing cells that survive only at long SRT are required for breaking down certain toxins and pollutants.
Short SRT plants are less expensive to construct and operate but are also less efficient in removing trace or emerging contaminants, such as many found in personal care products, pesticides, and pharmaceuticals. Longer SRT plants are generally more expensive and require more land area but are much better at removing trace organics and nutrients, such as nitrogen species (ammonia, nitrate, and nitrite). Most of the advanced treatment plants employ long SRT to produce higher-quality reclaimed water.
Through sampling and analysis, we could measure the overall presence of the varieties of ARGs we targeted. Samples were collected from the influent, the secondary treatment process (where the bacteria digest toxins), and the effluent.
While more research is needed to verify the results, our preliminary findings are promising. Though all ARG targets were consistently detected before and after the activated sludge processes at all the plants, analysis showed clear absolute reductions of ARGs from the influent to the effluent samples. Furthermore, long SRT–type plants showed greater reductions of ARGs than shorter SRT plants. The current wastewater treatment trend toward water reclamation, which relies on long SRT technology, would be encouraged if we can confirm these findings. However, we observed that relative ARG abundance has not gone down as much as we would like.
Our research is ongoing and will further investigate other aspects of bacterial activities and wastewater applications, including horizontal gene transfer and the effects of heavy metal toxicity to see if they affect ARG removal.
However promising, these results in no way reduce the need for better management of antibiotics. It is clear that antibiotic resistance is increasing worldwide. The WHO recommends that the world urgently invest in the research and development of new antibiotics to combat the disease- and infection-producing bacteria that have developed antibiotic resistance.
Our preliminary results suggest that wastewater treatment will reduce the introduction of ARGs to the environment. Even so, society must diminish the total volume of antibiotics we put into circulation. This remains a critical concern.
*Michael Stenstrom is a professor of environmental engineering at the University of California, Los Angeles. He has particular expertise in water and wastewater treatment issues.
References:
US Centers for Disease Control and Prevention. 2013. “Antibiotic Resistance Threats in the United States, 2013.” US Department of Health and Human Services.
Liu, Lin, Chaoxiang Liu, Jiayu Zheng, Xu Huang, Zhen Wang, Yuhong Liu, and Gefu Zhu. 2013. “Elimination of Veterinary Antibiotics and Antibiotic Resistance Genes from Swine Wastewater in the Vertical Flow Constructed Wetlands. Chemosphere 91(8): 1088–1093.