Introduction
Wastewater treatment plants are designed to clean water from solids and microbes making the water safe again for use. Sewers and other collection sites gather the water from homes, businesses, factories, farmland and deliver it to the plants for treatment. These treatment plants clean the wastewater and discharge the cleaned water into streams or recycle it for reuse. Generally speaking, this process has been perfected and wastewater is more than 90% clean after leaving the facility (1). However, newer pollution problems such as heavy metals, chemical compounds, and toxic substances, are much more difficult to treat and eliminate from wastewater – not all wastewater can be treated the same way. Large compounds, such as those produced by pharmaceutical manufacturers, are not as easily broken down and cause havoc on aquatic and human health. Although wastewater treatment is a priority and laws and regulations are in place to make sure certain standards are achieved, the current wastewater treatment processes are not equipped to handle the influx of pharmaceutical waste and as a result, a multitude of health impacts are developing because of the unknown destinations of pharmaceutical byproducts in wastewater.
Statement of the Problem
The Environmental Protection Agency (EPA) has described wastewater treatment as “a way to speed up the natural processes by which water is purified” (2). The two basic stages of treatment, primary and secondary, effectively remove solid waste and utilize biological processes to further purify the water. The final step in most wastewater treatment is to disinfect the water through the use of chlorine to kill pathogens that may still be present in the water; if done correctly, chlorination will kill 99% of harmful bacteria (2) left over in the water. When the wastewater treatment process was initially invented and implanted, it was sufficient for the workload required. With the increasing production and reliance on pharmaceuticals every year, a new problem has presented itself: traditional wastewater treatment methods are not satisfactory at removing or eliminating pharmaceutical byproducts from the water as it is being treated. Three studies completed between 2013 and 2017 each found that most conventional wastewater treatment plants are not designed to remove pharmaceuticals during treatment (3-5). The chemicals in most pharmaceuticals and personal care products typically undergo very little degradation during the treatment process and are often discharged back into the environment. Still present in the water or incorporated into a biosolid sludge (6), the chemicals have the potential to leach into the aquatic ecosystem and begin bioaccumulating within the organisms that live there.
A recent study by Scott et al showed that pharmaceutical manufacturing facilities (PMF) are contributing large amounts of pharmaceuticals and their byproducts to the environment through wastewater from their facilities–even after the water is being processed and treated at wastewater treatment plants (7). After analyzing 120 different pharmaceuticals, the concentrations measured in wastewater coming from PMF sites were significantly higher compared to wastewater that did not include water from PMF sites. This same study showed that wastewater treatment plants that take runoff from drug manufacturing sites are laced with antifungals, antihistamines, anti-inflammatories, and other drugs. The most commonly detected compounds were cholesterols, N,N-diethyltoluamide (an insect repellant), caffeine (stimulant), triclosan (antimicrobial disinfectant), carbamazepine, nicotine, and estrogenic compounds (7, 8). Similarly, a study by Ekpeghere et. al, showed that concentrations of personal care products (and their metabolites) were higher in human waste treatment plants compared to hospital wastewater treatment sites (9) – indicating there are some efforts being made to reduce this problem.
While the concentrations of pharmaceuticals left over in wastewater may be declining, a new situation that many are familiar with is developing: links between pharmaceutical wastewater and antibiotic-resistant bacteria have been identified.
Antibiotic Resistance
Antibiotic-resistant bacteria have been a growing health concern in recent years. In the United States alone, at least two million people are infected with antibiotic-resistant bacteria, resulting in nearly 23,000 deaths yearly (10). Infections caused by commonplace bacteria that were once curable with basic antibiotics are becoming more challenging and difficult to treat. The CDC released a report in 2013 listing off the 18 most dangerous threats (bacterial and fungal) to human health based on antibiotic resistance (11). The leading theory behind the growing antibiotic resistance is overuse of antibiotics and increasingly frequent exposure. More bacteria are exposed to a variety of antibiotics and through their natural genetic mutations and natural selection, bacteria are learning how to live in the presence of chemicals that once killed them. Beyond patients being prescribed antibiotics, bacteria are being exposed to antibiotic run-off from pharmaceutical wastewater treatment facilities. Wastewater containing antibiotics has high chemical oxygen demand and low biological oxygen demand making it very difficult to clean using typical wastewater treatments because of the reliance on biological processes (12).
Upon further examination into wastewater treatment, several studies have shown that not only are antibiotics present at high concentrations in the water, but the treatment process is a breeding ground for antibiotic-resistant bacteria. In one study, Li et. al examined four classes of antibiotics (tetracyclines, sulfonamides, quinolones, and macrolides) and their overall presence in a typical wastewater treatment facility. They did find that the antibiotics themselves were at least partially removed during the treatment process, but also that the number of bacteria with antibiotic-resistant genes bloomed (13). This finding is concerning because both of the main results identify two sources of antibiotic bacteria. The first, during the cleansing process, not all of the antibiotics are cleared from the water, meaning the effluent (the water deemed “clean”) still contains traces of these chemicals. The water then goes into the aquatic environment where naturally-occurring bacteria reside – creating more opportunities for these bacteria to gain exposure and develop resistance. The second contributing factor to increasing antibiotic resistance is the fact that antibiotic-resistant genes flourish in the current wastewater treatment process; the cleansing that is supposed to eradicate disease is inadvertently making a bigger problem with antibiotic-resistance.
As it turns out, antibiotic-resistance is not only an aquatic-based problem. During the wastewater treatment, bioaerosols containing bacteria are produced – an inevitable consequence of the current mechanism during cleaning (14). The spread of antibiotic-resistance can also occur through these bioaerosols. The bacteria that survived the cleansing process and were released in an aerosolized mixture are given a second chance in the environment. Here, they are able to gain exposure to those antibiotics that were unsuccessfully cleared from water coming from the treatment plants. Antibiotic-resistant bacteria are proliferating at high rates within the air environment surrounding wastewater treatment plants. A study that looked at the aerosolized outputs from a full-scale treatment facility found that more than 45% of the airborne bacteria were resistant to three or more antibiotics and some were found to have resistance to 16 types of antibiotics. The bacteria that were examined included Acinetobacter, Alcalignese, Citrobacter, Enterobacter, Escherichia, Klebsiella, Pantoea, Pseudomonas, and Sphingomonas (15).
Discussion
While a major focus of fighting antibiotic-resistance is within the healthcare community by prescribing fewer antibiotics and strongly encouraging every patient to fully finish their antibiotics when prescribed them, a closer look into how wastewater from pharmaceutical plants is treated and cleaned will be a necessary step in this battle. When exploring options for the future of wastewater treatment and antibiotic-resistance it is prudent to look at current laws, technological aspects, and prevention strategies.
Applicable Laws—The Environmental Protection Agency (EPA) plays a major role in overseeing wastewater treatment and ensuring the effluent coming from these facilities is compliant with regulations. Specifically, the Clean Water Act (CWA) of 1972 granted the EPA the authority to regulate wastewater effluents and set pollution and wastewater standards. The CWA also established the National Pollutant Discharge Elimination System (NPDES) that requires industries to obtain permits before discharging pollutants from their facilities (16). In addition to the NPDES, the EPA also created the Pharmaceutical Manufacturing Effluent Guidelines and Standards in 1976. These guidelines and standards lay out exactly how wastewater containing fermentation products, extraction products, and chemical synthesis products should be handled and what the acceptable concentrations of byproducts in the resulting effluents are. The Federal Regulations are applicable to any facility that “processes wastewater discharges resulting from the research and manufacture of pharmaceutical products”(17). Fulfillment with these regulations is mostly controlled at the state level – the EPA is reliant on states to measure on-site compliance and aid with filling out and complying with NPDES permits. It is within the EPA’s authority to penalize facilities failing to follow these guidelines, usually in the form of a fine (18). Reevaluating these current guidelines to reduce the acceptable concentration of antibiotics after treatment will help lower the tolerable level of pharmaceuticals (and antibiotics) in wastewater effluents.
Technological Aspects/Prevention Strategies—Currently, research is being conducted to determine more efficient and effective ways to treat pharmaceutical wastewater. The four prominent areas that are under further investigation are electrocoagulation, up-flow anaerobic sludge blanket (UASB) reactors, and ozonation.
Electrocoagulation is a low-cost alternative from the standard chemical coagulation process in wastewater treatment. In electrocoagulation, an anode is used to destabilize contaminants in wastewater instead of mixing the solution with chemicals to form a precipitate. Typically, the floc from electrocoagulation is more stable and binds less water (in comparison to chemical coagulation) making it more easily removed through sedimentation or filtration. Additionally, electrocoagulation, in comparison to traditional methods, produces less sludge and faster pollutant removal (19). Proving to be extremely effective in removing pharmaceuticals from wastewater, particularly with antibiotics such as diclofenac and amoxicillin (20), perhaps more efforts should be made to transition to incorporating electrocoagulation more frequently in wastewater treatment facilities.
UASB reactors are another alternative process in wastewater treatment. Instead of the normal process where water flows down or through a filter, in an UASB reactor, wastewater enters the tank from the bottom and flows upward where it filters through a suspended sludge blanket. There are many benefits to using UASB reactors that include a reduction in the biological oxygen demand, an increased ability to withstand high organic and hydraulic loads, decreased sludge production, and production of biogas that can be used for energy (21). Research is going into determining the effectiveness of using UASB reactors as a pretreatment for pharmaceutical wastewater. Lots of variable results indicate a need for further research (12), but UASB reactors pose as another possible method to remove pharmaceuticals from wastewater. (See Appendix A, Figure 1)
In ozonation, ozone molecules attack and rupture target molecules and produce byproducts that are easily biodegradable. Overall, ozone treatment usually improves the biodegradability of the wastewater. This improvement is essentially necessary for complete degradation of pharmaceuticals found in wastewater because of their ability to resist typical biological treatment (22). Relatively inexpensive, this is another form of wastewater treatment that should be further investigated and implemented.
All of these technologies are proving to be overall more cost-efficient, more effective at eliminating pharmaceuticals from wastewater, and only slight modifications to what is currently being done.
Conclusions
There is growing concern of pharmaceuticals and pharmaceutical byproducts being inadequately removed from wastewater as it is treated by normal methods. These leftover chemicals not only cause environmental damage and increase the amount of chemical exposure individuals have on their daily lives, but are also playing a role in the development and propagation of antibiotic-resistance. In order to combat this issue, methods that have shown to improve the cleansing process of wastewater, especially from pharmaceutical facilities. As mentioned above, there is lots of research going into developing and improving alternative methods. It appears that electrocoagulation is one of the preferred methods as there were about six companies in the United States currently working with this technology in 2014 (23). Utilizing more biological methods are also being considered: adding membrane bioreactors to the treatment process and adding the fungus T. versicolor to unprocessed sludge (24, 25). In all cases, fewer amounts of pharmaceutical concentration were left over after the addition of any of the aforementioned processes.
Unfortunately, the biggest challenge preventing the immediate implementation of the majority of these processes is time and money. Making progress in the wastewater treatment process is reliant upon implementation of new technologies and the sooner it occurs, the better outcomes will be. These new technologies will require training, changing of protocols, and will be dependent on whether or not the facilities are able to adapt to their usage. There is hope for the future of wastewater treatment and eliminating its influence on the growing level of antibiotic resistant bacteria – it will depend heavily on industry recognizing the issue, the EPA stepping in to make regulation changes, and those same industries being willing to adapt to promising solutions.