Rise of the Superbugs

 Measures need to be taken at international, national, community, hospital and individual level by healthcare workers including doctors, nurses, pharmacists and the patients as well in order to control the problem of antimicrobial resistance effectively in a time-bound manner. 

Alexander Fleming known as the “Father of Antibiotics” while receiving Nobel Prize for the discovery of Penicillin in 1945 had forecasted in his acceptance speech, “But I would like to sound one note of warning the time may come when penicillin can be bought by anyone in the shops. Then there is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non‐lethal quantities of the drug and make them resistant”. Today humanity is witnessing his golden words turning into a harsh and bitter reality with under-, over- and misuse of antimicrobials leading to the emergence of resistance among bacteria and other micro-organisms. Day is not far when a minor injury, disease or surgery could result into the death of a person as a result of untreated infection due to antimicrobial resistance (AMR). Currently, at least 700,000 people die each year due to drug-resistant diseases, including 230,000 people who die from multidrug-resistant tuberculosis (WHO, 2019). British government appointed antimicrobial resistance review committee chairman Jim O’Neil predicted in 2016 that by the year 2050 there could be an estimated 10 million deaths annually as a result of AMR and it could cost the world economy a whopping 100 trillion dollars. An ever-growing list of infections such as pneumonia, tuberculosis, systemic infections and gonorrhoea are becoming harder and sometimes impossible to treat as antimicrobials continue to become less effective. Resistance has also rapidly emerged to sulphonamides, penicillins, tetracyclines, macrolides, fluoroquinolones and cephalosporins. 

Though some critics term these figures projected by Jim O’Neil as exaggerated, fact of the matter is that as per World Health Organization (WHO, 2020) high rates of resistance against antibiotics frequently used to treat urinary tract infections, sepsis, sexually transmitted infections and some forms of diarrhoea have already been reported world-wide, indicating that we are steadily running out of effective antibiotics. For instance, the rate of resistance to Ciprofloxacin, an antibiotic commonly used to treat urinary tract infections has increased from 8.4% to 92.9% for Escherichia coli and from 4.1% to 79.4% for Klebsiella pneumoniae in countries reporting to the Global Antimicrobial Resistance and Use Surveillance System (GLASS). WHO-GLASS has further reported that the resistance in Klebsiella pneumoniae, that can cause life-threatening infections, to the last resort treatment i.e., carbapenem antibiotics has spread to all regions of the world. K. pneumoniae is a major cause of hospital-acquired infections such as pneumonia, bloodstream infections and infections among newborn and intensive-care unit patients. Colistin is the only last resort treatment for the life-threatening infections caused by carbapenem resistant Enterobacteriaceae i.e., E. coli, Klebsiella, etc. However, astonishingly bacteria resistant to colistin have also been detected in several countries and regions, causing infections for which there is no effective antibiotic treatment available at present (WHO, 2019). Thus the world is fast heading towards what some people call as ‘antibiotic apocalypse’ and others term as ‘post-antibiotic era’ as a fall-out of multi-drug resistant or pan-resistant micro-organisms known in common parlance as ‘superbugs’. Superbugs exhibit super-resistance and like super-computers and self-automated AI machines turn uncontrollably and unimaginably hostile, wreaking havoc to the ailing lot like tuberculosis patients suffering from multi-drug resistant, extensively drug resistant and totally drug resistant forms of tuberculosis. 

Need of the hour is to take adequate prevention, management and control measures well in time to stop the spread of resistance among microbes though many scientists believe it to be an evolutionary process wherein micro-organisms are believed to mutate to resistant forms as a result of natural selection and environmental survival pressure created by antibiotics or the constrained environment. Intrinsic or acquired mutations allow them to survive and live on to reproduce. Then they pass this trait to their offsprings, which would be a completely resistant generation. Bacteria are remarkably adaptable organisms with an innate ability to circumvent damage if exposed to a toxic environment (Floris et al, 2020). Since the development of the first antibiotic less than a century ago, there has been an exponential growth in antimicrobial resistance that is disproportionate to the rate at which antibiotics are introduced. In 2019 WHO identified 32 antibiotics in clinical development that address the WHO list of priority pathogens, of which only six were classified as innovative. Since 1990, only three novel-class antibiotics have been launched (pleuromutilins, lipoglycopeptides, and oxazolidinones), although many derivatives of older classes were also launched (Baker et al, 2018). 

WHO has declared that AMR is one of the top 10 global public health threats facing humanity. It requires urgent multisectoral and multi-dimensional action in order to achieve the United Nations Sustainable Development Goals (SDGs). Superbugs are omnipresent in the biosphere Continued resistance is rapidly eliminating treatment options for patients, and the cost burden to treat a multidrug-resistant infection is steadily climbing, reaching more than $2.2 billion annually in the United States.  Universally, the market consumption rate of antibiotics is assessed to range from 0.1 to 0.2 million tons yearly (Wise, 2002). Antibiotics are extensively used in medical, veterinary, and agricultural platforms for therapeutic, prophylactic, metaphylactic and growth-promoting purposes. The overall quantity of antibiotics used worldwide in agriculture is estimated to range between 63,000 and 240,000 tons, with beta‐lactam antibiotics like penicillins, cephalosporins, and carbapenems being the largest group of antibiotics consumed (50%–70%) by humans (Kumar & Pal, 2018). 

Many strategies for avoiding, inhibiting, or bypassing resistance mechanisms in pathogens have been attempted. The most notable successes in such endeavors have been with the β-lactam antibiotics. Clavulanic acid and related compounds are potent inhibitors of β-lactamase enzymes and are frequently used in combination with the β-lactam antibiotics. These combinations have been highly effective but bacteria have found a way to outsmart us: a number of β-lactamases that are refractory to inhibition by clavulanate have appeared. To date, research to extend this approach to other classes of antibiotics has not been successful (Davies & Davies, 2010). Antibiotic resistance has been found in most bacteria, but several bacteria are particularly problematic and are becoming common among hospital-acquired infections that include Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacteriaceae commonly referred to as ESKAPE pathogens (Floris et al, 2020). In 2017, the WHO published a list of bacteria where new antibiotics to tackle them are needed urgently and grouped them according to their priority as critical, high and medium, with a view to encourage research and development of new antibiotics. 

AMR can be overcome to a large extent by referring to nature to develop naturally derived agents with antibacterial activity on novel targets such as bacteriophages, Odilorhabdins (ODLs), peptidic benzimidazoles, quorum sensing (QS) inhibitors and metal-based antibacterial agents and by deactivating the mechanism of resistance, like the action of the β-lactamase inhibitor antibiotic adjuvants (Breijyeh et al, 2020). Strategies relying on phage therapy, probiotics, CRISPR technology, faecal transplantation and host immune response biomarkers are also being explored as novel approached to combat AMR. Innovative vaccine technologies, such as reverse vaccinology, novel adjuvants, and rationally designed bacterial outer membrane vesicles, together with progress in polysaccharide conjugation and antigen design, have the potential to boost the development of vaccines targeting several classes of multidrug-resistant bacteria (Das et al, 2017). Furthermore, new approaches to deliver small-molecule anti-bacterials into bacteria, such as hijacking active uptake pathways and potentiator approaches, along with a focus on alternative modalities, such as targeting host factors, blocking bacterial virulence factors, monoclonal antibodies, and microbiome interventions, all have a significant potential to counter AMR (Baker et al, 2018). 

Unless and until adequate prevention and control measures are not adopted in a concerted fashion by all the stakeholders, it is not possible to combat AMR through novel and innovative approaches. A mix of conventional and novel approaches alone is going to yield best results. Measures need to be taken at international, national, community, hospital level as well as at individual level by healthcare workers including doctors, nurses, pharmacists and by the patients in order to control the problem of AMR effectively. All stakeholders need to join hands and act in an integrated and collaborative manner complementing and supplementing each other in their efforts towards preventing and controlling AMR. All our hospitals need to devise their own infection control and antibiotic use policies besides framing standard treatment guidelines for infectious diseases and constituting Drugs and Therapeutics Committees and formulating Hospital Formularies (Geer, 2017). There is a need to conduct culture tests for determining antimicrobial sensitivity first and then only prescribing antibiotics. Rampant sale and use of antimicrobial drugs that have been listed and notified in 2013 under Schedule H1 of the Drugs and Cosmetics Act, over-the-counter sans any prescriptions written by qualified physicians and their indiscriminate sale by unqualified pharmacists at retail sale outlets need to be curbed with tough regulations and strict law enforcement. Need of the hour is to implement this provision strictly on war-footing basis failing which it will be impossible to avert AMR. Indiscriminate sale and use of antibiotics cannot be taken lightly anymore. Jammu and Kashmir government must come up with a robust and comprehensive action plan of its own for the containment of AMR as soon as possible. Other measures that the government needs to take for the prevention and control of AMR have been enumerated in another article of mine published in 2017 on “Averting Antibiotic Apocalypse in J&K”.

Scientific progress - hallmark of a dynamic society

 Fostering a creative mindset and nurturing academic freedom can spur innovations in the curriculum that in turn will churn out graduates with innovative ideas and ultimately result in substantial scientific progress in terms of innovations and inventions 

Pace of progess made in science and technology is the hallmark of a dynamic and vibrant society as twenty first century belongs to the science and technology and any nation that fails to keep pace with latest trends and recent advances made at the global level in this sector will draw a flak and eventually be despised as an unenterprising and regressive nation. Such a nation will also face a lot of difficulties in meeting with the needs, demands and challenges thrown by the potential threats and dangers of the twenty first century including human existential threats, food, water and fuel scarcity threats, cyber security and climate change threats, threats posed by lab designed viruses and bacteria and nuclear threats. Therefore there is need to prepare vision documents and perspective plans at the national as well as regional level in which long range targets are set in advance for a period of 10, 20 or 25 years for making some tangible and time bound progress in the field of science and technology while at the same time promoting innovations and inventions.

Progress made in science and technology by any nation at present can be assessed by the quantum of adoption of innovations and inventions made at the global level, degree of innovations and inventions contributed by that nation to the world and the level and quality of education and awareness among its citizens regarding some of the most burning and contemporary issues in science and technology. Former Principal Scientific Advisor to the Govt. of India R Chidambaram has in his Current Science article added one more dimension to this kind of evaluation by writing that “scientific research publications are one of the quantitative measures for the basic research activity in a country” and that “the root cause for stagnancy in the number of research publications from India seems related to the fact that talented and bright young students have not been opting for careers in science in recent years”. In another article he has emphasized that “the science and technology foresight involves forecasting of possible futures, taking into account existent as well as emerging technologies, with the objective of achieving the maximum economic, social and security benefits”.

In order to stay relevant and be counted in the modern world any nation has to strike a fine and delicate balance between being a producer and a consumer of the fruits of science and technology.  Nations that are only good at consuming and reaping the benefits of science and technology and are not performing fairly well at producing the innovative products for others will ultimately be thrown out of the race towards scientific progress and development and they will have to bear with little or no opportunities to earn sizeable revenue from the global markets. This will relegate them to the back benches and they will eventually lose all their influence as well as opportunities of emerging as global leaders. In order to avoid any such situation developing nations will have to undertake a major overhaul of their S&T curriculum, training, innovation incubation, entrepreneurship development and the whole education system at school, secondary and higher education levels.

Education and awareness about emerging areas in S&T

Creating awareness and imparting education about emerging areas in science and technology is the first step towards planting a seed that will eventually grow into a tree and bear sweet fruits for all to relish. Education and awareness needs to be enhanced about contemporary emerging areas in science and technology including artificial intelligence,  cloud computing, data analytics, robotics, space technology, nanotechnology, biotechnology and molecular biology, stem cell technology, gene therapy, 3D printing, quantum computing, biodiversity and ecology, point-of-care testing, nuclear and bio-physics, internet-of-things, micro-electrical mechanical systems, crypto-currencies, cancer vaccines, genetically modified foods, cell culture and in-vitro fertilization etc. There is a need to enhance the knowledge-base, training, skills, competencies, expertise, interest and familiarization in these areas among the youth. Once they are sensitized about all important aspects of these areas they can pursue higher education in them and acquire sufficient academic acumen and technical prowess to forge innovative solutions in these areas. This will help generate a technically competent workforce ready to venture into these areas and produce tangible results. Curricular updation at a large scale at school, college and university levels shall be required for meeting this challenge of change.

Adopting global innovations in our day-to-day life

Adopting global innovations and inventions in our day-to-day life is as important as knowing about them. Apart from knowledge, data is going to be the new capital in the twenty first century.  World is heading towards a mad and bitter race for data in the coming years. We need to march ahead in tandem with rest of the world lest we shall lag behind and be overstepped by other nations in this race. It is said that burgeoning consumerism leads to a faster adoption of the breakthrough innovations. As per William Pollard, “Learning and innovation go hand in hand; the arrogance of success is to think that what you did yesterday will be sufficient for tomorrow”. Greek philosopher, Hiraclitus says, “The only constant in life is change”. Change calls for innovation and innovation leads to progress. “Without change there is no innovation, creativity, or incentive for improvement. Those who initiate change will have a better opportunity to manage the change that is inevitable”, William Pollard has said. Political will of the government for adopting global innovations is of key importance. Unless there is political will no tangible innovation and progress in S&T is practically possible. As per Bill Gates, “Governments will always play a huge part in solving big problems. They set public policy and are uniquely able to provide the resources to make sure solutions reach everyone who needs them. They also fund basic research, which is a crucial component of the innovation that improves life for everyone”. 

Contributing our bit of innovations and inventions 

While it is important to gain sufficient knowledge and know-how about innovations and inventions made globally and also to adopt them to every possible extent in our day-to-day life, it is equally important to keep contributing our share of innovations and inventions on persistent basis with a view to stay technologically relevant as well as reliable in the international arena. Our academic and research institutions need to innovate themselves first in order to be capable and competent to contribute innovations and inventions that are acceptable and buyable in the global markets. Peace and stability as well as unity and economic strength of a nation assumes utmost importance in being able to come up with innovative solutions to the problems and challenges thrown by twenty first century. Nations facing internal strife, discord and distress socially, politically and economically will find it increasingly difficult to compete in the global innovations market. A creative mindset and liberal ideology as well as academic freedom alone can spur innovations in the curriculum that in turn will churn out graduates with innovative ideas and ultimately result in substantial noteworthy scientific innovations and inventions. 

Global scientific community can work in tandem across cultures and nations, bridging political divides to encourage innovations and engineer inventions all across the world. In order to promote science education and scientific temper among our progeny at school, college and university levels, we need to have students eager to investigate the wonders of the natural world, teachers steeped in scientific knowledge and masterful at guiding students' investigations, parents and school administrators who value, expect and support standards-based science education, leaders in business and government who understand the importance of science education for all citizens. Scientific temper is considered to be the best answer to ignorance, superstition and arrogance. A citizen without scientific literacy can have no basis for discerning the valuable from the worthless. One who is scientific literate is able to critically interpret, analyze and evaluate claims and not just believe the hearsay or go by the common public perception. He knows how to research relevant data, examine evidence and draw appropriate conclusions because theories are judged by results. Sincere, dedicated and collective efforts alone on part of all these stake-holders can get us rid of the ills that are plaguing our understanding of, adoption and contributions to science and technology. 

Coronavirus disease outbreak has exposed many chinks in our armour. It has virtually caught the whole world napping in terms of our preparedness to combat a crisis of this magnitude and mange its consequences well. Higher educational and health institutions as well as research centres in developing countries like India have not come out with sufficient and substantial new knowledge, guidance, resources, policy papers or blueprints to counter the economic, sociological, psychological, medical, commercial, humanitarian and health-related challenges posed by the pandemic. We have turned into consumers of knowledge and resources emerging from rest of the developed world necessary for tackling its fall-outs. Therefore we need to learn this bitter lesson from the ongoing crisis and prepare for more such challenges and other possible, similar disasters in the coming decades. Road to our preparedness towards such unprecedented situations leads through an impressive progress in Science and Technology alone.