The rise of antibiotic resistance in water: a danger to humankind and the environment
The discovery of the first antibiotic, Penicillin, by Alexander Fleming is, without a doubt, the turning point in the evolution of modern medicine. Antibiotics are the primary treatment choice for bacterial infections like chlamydia and gonorrhoea. Antibiotic treatment became widespread after Penicillin use in 1947 to treat World War II soldiers. It also underpins surgeries, chemotherapy for cancer and joint replacements.
The golden antibiotic era from 1950 to 1960 saw massive advancement in treating infections that were once deemed incurable, and many concluded that common infections are not going to kill them anymore. Antibiotics, at the core, are natural substances produced as a defence mechanism by bacteria, to either inactivate or destroy the competitor microbes for their survival. Humans leveraged this defence mechanism of antibiotic production as a weapon against its producers (the bacteria) utilizing it as a form of therapeutic intervention.
However, the bacterial population found ways to bypass the threat of antibiotic action leading to the emergence of antibiotic-resistant bacteria like methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus species (VRE). The resistant bacteria were selected for survival overtime via the evolutionary process of natural selection due to their ability to tolerate sublethal dosage levels of antibiotics. In addition, there are reports to prove that antibiotic resistance has existed even before the widespread use of antibiotics, suggesting that antibiotic resistance may not be a consequence of antibiotic overconsumption.
Alexander Fleming did warn about antibiotic resistance and its consequences in 1945, even before the first case of penicillin resistance was documented in 1947, two years after his warning.
The pharma industry made considerable investments in producing new classes of antibiotics every time an antibiotic failed to treat a bacterial infection. However, the beginning of the 1980s saw a gradual rise in antibiotic resistance despite the attempts made by the pharmaceutical industry to curb antibiotic resistance. Eventually, the antibiotic pipeline began to dry up, and a new antibiotic became a rare commodity. Over the last three decades, not a single new class of antibiotics have been introduced to the market due to the inability to cope with the spread of bacterial resistance to antibiotics. In fact, only less than 5% of investment in research and development of the pharma industry was allocated to antibiotics development between 2003–2013 upon realizing that more antibiotics are not the solution to counter the threat of resistance.
So, what is the significance of antibacterial resistance, and why does the World Health Organization consider it the third-largest threat to global public health in the 21st century?
Antibiotic resistance is when a bacterium develops mechanisms to protect itself from antibiotic action. According to the WHO, the urgent need for treatment options for infections like pneumonia as of February 2017, due to the inefficacy of antibiotic therapy, shows the breadth of this issue.
The problem is so acute that currently 700, 000 people die every year from resistant infections. If we lose the fight against antibiotic resistance, then the future generation will bear the brunt of the post-antibiotic era, especially in middle and low-income countries. Moreover, the death toll could mount to 10 million per year or one person every three seconds, by 2050 if the dangerous trend continues. In other words, one person could lose their life every three seconds by 2050 if the rapid spread of antibiotic resistance is not mitigated. Apart from human loss, antibiotic resistance is also linked to substantial economic costs, which can reach a cumulative 100 trillion USD by 2050 unless proactive solutions are taken to tackle the challenge, according to the analysis of Jim O’Neill, a British economist. The World Bank Report of 2016 mentions that a staggering 8 million to 24 million people could enter poverty due to challenges posed by antibiotic resistance, which shows that tackling the issue is integral to the development of the long-term economy of countries. All 193 countries of the United Nations, accounting for 98% of the world, have declared to combat antibiotic resistance upon understanding the issue’s magnitude from an economic perspective. If countries do not take coordinated steps to isolate the problem, the negative economic impact will be felt across all communities.
Over-the-counter drugs without medical prescription, incomplete course of treatment or overuse of antibiotics for infections that cannot be tackled with them have led the bacteria to outsmart us in developing antibiotic resistance in hospital settings. Over the last two decades, overexploitation of antibiotics in sectors beyond hospital settings like agriculture, livestock and aquaculture, has accelerated the rate at which bacteria in the environmental compartments are exposed to amounts of antibiotics that are not lethal to them resulting in the spread of resistance. So, the dangerous trend is not antibiotic resistance but the dissemination of antibiotic resistance in the environment, particularly in water bodies.
Water plays a major role in the spread of antibiotic resistance
The dissemination of antibiotic resistance in the aquatic environment is considered the primary reservoir of antibiotic resistance since unmetabolized antibiotics and residues from hospital waste, agricultural runoffs, effluent from animal feed, aquaculture feeds, and drug manufacturing centers are disposed into the water sources. Moreover, the consumed antibiotics end up in human faeces and animal waste, to eventually get dumped into water.
The presence of antibiotic contaminants in water systems can enable horizontal transmission of resistance genes between bacteria already resistant to the same class of antibiotics, to sensitive commensal or pathogenic bacteria, eventually making a pool of antibiotic-resistant bacteria. Horizontal gene transmission occurs in three main ways; transformation, transduction and conjugation. The water treated in a wastewater treatment plant is reused in anthropogenic activities, worsening the already prevalent threat to the ecosystem. For instance, the entry of resistant bacteria into the human gut upon consumption of treated drinking water can transfer the resistance gene from resistant bacteria to the normal flora. Future contact of a pathogen with the person can lead to the failure of antibiotic treatment as the normal resistant flora can swap genes with the pathogen making it resistant. The presence of antibiotic contaminants in treated water and sludge indicates the lack of technicality in treatment plants to break down antibiotics, particularly in countries like India, where the scale of low-cost antibiotic production is vast.
A research study conducted in a Hyderabad wastewater treatment plant receiving water from 90 pharmaceutical factories in different regions revealed that bacteria were resistant to 30 out of 39 test antibiotics. Several studies indicate that traveling and displacement of people also contribute to the transmission of antibiotic resistance genes, which poses an ominous threat to the global health care system. Sri Lanka is not an exception to antibiotic resistance in the water. Varying levels of resistance were found against E.coli in Kelaniya River based on the seasonal profile.
Strategies to combat antibiotic resistance in aquatic systems
Several interventions can be implemented to reduce/ avoid antibiotic resistance, even if we cannot stop it from happening. The first challenge to overcome is access to clean water and sanitation infrastructure, preventing the spread of pathogenic infections like diarrhoea since it could drastically reduce the consumption of antibiotics thereby mitigating the rapid rise of antibiotic resistance. According to the Review on Antimicrobial Resistance (AMR), chaired by economist Jim O’Neill and commissioned by the UK Prime Minister in 2014, the introduction of improved water and sanitation infrastructure in four middle-income countries (India, Indonesian Nigeria and Brazil) could reduce the number of water and sanitation-related diarrhoea being treated with antibiotics. Campaigns like the ‘Clean India Mission’ in India that proactively make an effort to provide safe water can create a positive paradigm shift in the road to fighting antibiotic resistance.
In collaboration with experts in the field, policy-makers and the government can make a concerted effort and investment decisions to minimize the unnecessary use of antibiotics across humans, animals and the environment. For example, prohibition of the use of antibiotics as growth feed additives in the animal husbandry of European countries is a great strategy that could minimize the resistance spread, and poorer countries require this urgent measure now more than ever. Regulators can set minimum standards in the pharmaceutical industry to control the release of contaminants into water bodies. Information on the site and surrounding context of antibiotic manufacturing center can serve as a guide to measure the stringency level of environmental regulations, pharmaceutical companies should comply with and propose on-site wastewater treatment plants for the efficient disposal of antibiotic waste and antibiotic-resistant contaminants. Detection of antibiotic resistance genes in water across different water treatment facility components can be done as part of a risk assessment program to understand the extent of risk linked with the dissemination of antibiotic resistance genes in drinking water sources.
Another way to reduce the spread of antibiotic resistance is by installing steps to either break down antibiotics or filter the residues and resistant bacteria using a membrane bioreactor with ozone and activated coal. These are significant steps taken by Sweden to counter the threat of antibiotic resistance in water. Enzymes fastened to toilet bowls that can cleave antibiotics is another great initiative by Sweden to reduce the spread of antibiotics. Actions like composting, liming and aerobic or anaerobic treatment can reduce the antibiotic resistance gene levels. The sludge, animal manure and sewage effluent have to be treated in wastewater facilities to reduce the antibiotic concentration before its release into aquatic compartments.
Equal attention to antibiotic resistance is required, as much as the topic of climate change, to avoid an era where there would be no more antibiotics that could treat an infection as simple as bacterial food poisoning. Even if we cannot eradicate antibiotic resistance, formulating a coordinated action plan by each country can slow down the dissemination of global antibiotic resistance until new drug alternatives with zero resistance can replace antibiotic treatment.
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