Global dependence on antimicrobials
It is hard to imagine a world without antimicrobials. From healthcare to agriculture; antimicrobials underpin the microbiological safety of our modern world. In agriculture, antibiotics are used to control microbial pathogens and promote growth in livestock animals. In 2017, the FDA reported that over 10 million kilograms of antimicrobial drugs were sold for use in food-producing animals, 51 % of which are medically important. In human medicine, antimicrobials are dispensed within hospitals and in the community to prevent or treat infectious disease. In 2014, the Centers for Disease Control (CDC) reported 266.1 million oral antibiotic prescriptions, and the most recent figures from the EU report a median consumption rate of 17.9 defined daily doses of antibiotics per 1000 inhabitants. Unfortunately, the lifecycle of an antimicrobial does not end with the human or animal to which it was administered.
The lifecycle of antimicrobial compounds
Depending on the exact antimicrobial and its route of application, between 10 to 90 % may be excreted in its active form. Taking the example of a human patient prescribed with oral amoxicillin to treat strep throat, after administration, more than 50 % of the antibiotic may be excreted, entering the sewage system. From here, it will be transported to waste-water treatment plants (WWTPs) and subjected to mechanical, biological and chemical treatments. In spite of these treatments, large amounts of amoxicillin and other antimicrobials persist and are introduced, with the treated water, into rivers and lakes. Subsequently, they spread through the natural environment, as an unseen pollutant, interfering with natural systems far beyond their original administration.
The devastating effects of antimicrobial contamination
Antimicrobial contamination in the environment has been linked with high levels of ecotoxicity and the rapid spread of antimicrobial resistance. Recent research has revealed the toxic effects of antimicrobials released into the environment on primary producers, such as cyanobacteria and algae. The concern is that, like other bioactive chemical pollutants, the antimicrobials will destabilize entire ecosystems from the bottom up. Beyond the direct ecological effects of antimicrobials in the environment, the emergence of antibiotic resistant microbes is a major global concern for human health care. The prevalence of multi-drug resistant microbial pathogens is rising, and many are far more challenging to treat. For instance, the WHO reported the treatment success rate of extensive drug resistant tuberculosis (XDR-TB) as only 34 % in 2015, compared with 82 % for non-resistant TB.
As natural producers of antibiotics, bacteria have innate mechanisms to interact with this class of chemical. Furthermore, compared with animals, bacteria can evolve extremely rapidly. These factors dramatically increase the probability of bacteria spontaneously developing resistance in response to external selection pressures, such as the presence of antimicrobials. With more and more antimicrobials being released into the environment, there is an increasingly strong selection pressure for antibiotic resistant bugs to thrive and eventually find their way back into humans. A particularly concerning environment is the WWTPs, which may act as incubators for antibiotic-resistant human pathogenic bacteria ,. One study of four U.S. WWTPs, detected methicillin resistant Staphylococcus aureus (MRSA) in 50 % of wastewater samples, including wastewater effluent.
Removing antimicrobial contaminants from the environment
The problem is that WWTPs were never designed to remove complex chemicals. Dr Rachel Gomes, a lecturer in Chemical and Environmental Engineering at the University of Nottingham, explains “WWTPs were created in the 1850s, and they were designed to remove pathogenic microorganisms. WWTPs were never designed to remove these emerging pollutants”. WWTPs represent a key target for breaking the cycle of antimicrobial contamination in the environment and removing the selection pressure for antimicrobial resistant bacteria. However, antimicrobials present a significant challenge for existing wastewater purification methods, which can be categorized by mechanism of action into biodegradation, chemical oxidation and adsorption.
Most WWTPs currently use biodegradation as the primary method to degrade or remove organic molecules from wastewater. Biodegradation processes rely on micro-organisms and solid biomass in the wastewater sludge to degrade and adsorb organic molecules, before separation by sedimentation or membrane filtration. However, these methods have generally demonstrated a lower efficacy for complex pharmaceutical molecules, such as antimicrobials. Dr Adriano Joss is a Process Engineer at the Swiss Federal Institute of Aquatic Science and Technology (EAWAG), he states that there are “50 compounds that are typically discussed in the context of micropollutant removal. Biological methods remove only around 20 % of these compounds”.
Chemical oxidation has been proposed as a pre-treatment to deactivate complex organic molecules before they are fully decomposed in the biodegradation steps. This can be achieved by addition of oxidizing chemicals, including hydrogen peroxide, ozone, inorganic catalysts, or through electrochemical methods. Electrochemical oxidation methods include the use of a boron-doped diamond anode, which attained complete mineralization of effluent organic matter containing 29 target pharmaceuticals and pesticides. Dr Gomes states “advanced oxidation methods reduce the levels of these chemicals, but they have extremely high energy costs, they produce air emissions and there are potentially dangerous side products”, indeed the boron-doped diamond anode researchers raised environmental concerns about the generation of chlorate and perchlorate species, and the potential effects of their release into the environment.
Finally, there is adsorption of the organic micropollutants on a solid particle, which can be removed from the effluent by filtration. Adsorption can be achieved through hydrophobic van der Waals interactions or ionic interactions, and common particle materials include granular activated carbon, activated alumina, zeolites, peat and metal-organic frameworks. According to Dr Joss, activated carbon represents the most scalable option, “activated carbon is very cheap, easy to get and the activation process requires only an oven with controlled temperature.” Dr Gomes agrees “we use activated carbon; it can be manufactured at scale. The challenge with adsorbents is will it take the pollutant of interest, and are you able to manufacture enough of it?” Nevertheless, activated carbon is often portrayed as a costly and burdensome option in the literature due to its regeneration process, which requires high temperature treatments and atmospheric control.
Several new adsorbent species are being explored at lab-scale for their potential to remove organic micropollutants and be regenerated efficiently. One such species is cyclodextrin, a naturally occurring sugar more commonly associated with air pollutant removal products such as Febreze®. In recent years, cyclodextrin polymers have found a new application in water purification. Insoluble cyclodextrin polymers are proposed as an inexpensive, sustainably produced alternative to activated carbon. Recent research from Northwestern University reported the production of a high surface area, crosslinked β-cyclodextrin polymer which sequesters organic micropollutants at rates 15 – 200 times greater than those of activated carbons. Furthermore, the regeneration process requires only a mild washing procedure with no loss of performance.
There is widespread agreement on the need to reduce antimicrobial contamination in the environment. This is motivated, firstly, from the perspective of longer-standing environmental initiatives to protect natural ecosystems from organic micropollutants. The United Nations’ most recent report provided a stark reminder of mankind’s colossal footprint on a fragile plant, stating that a staggering 1 million animal and plant species are now on the brink of extinction. Secondly, there are rapidly amassing concerns regarding antimicrobial resistance and human health.
With a rich research landscape of new and improved methods for degradation and removal of challenging organic micropollutants, it can seem that we are not far from reaching a resolution. However, the engineer’s perspective resonates the issues of scalability and practicality. For any new decontamination technology, these factors must be at the forefront. “Is it scalable and practicable?” is every bit as important as “does it degrade/adsorb our target chemical?” Dr Gomes eloquently summarizes “You have to look at these treatment technologies holistically, it’s about translating research into practicality”.