By: Dr Umar Bin Farooq

If we fail to act, we are looking at an almost unthinkable scenario where antibiotics no longer work and we are cast back into the dark ages of medicine

Antimicrobials are the drugs that destroy microbes, prevent their proliferation, or prevent their pathogenicity. Since the accidental discovery of penicillin by Alexander Fleming, antibiotics have saved millions of lives and thus, truly named as “wonder drugs”. The advent of antimicrobials has revolutionized medicine by controlling a number of infections. Antimicrobials are widely used for therapeutics, prophylaxis, and as growth promoters too. Their blue diamond role in the preservation of infection among humans & animals can be ratified with no compunction. On the flip side, with the ubiquitous use of antibiotics, mankind is at the verge of emerging antimicrobial resistance. Lack of properly observing the dosage regime, indiscriminate self-medication, quackery tactics, and poorly administered national action plans are major contributing factors for emerging antimicrobial resistance. Thus, senses for the rational use of antimicrobials must prevail. As to put in the words of Alexander Fleming:

“It is not difficult to make microbes resistant to penicillin in the laboratory by exposing them to the concentrations not sufficient to kill them.”

Antimicrobial resistance has been recognized as a principal public health concern with increasing magnitude. It is now accepted as a global multifaceted problem with several underlaying factors. The World Economic Forum has urged to add antimicrobial resistance in global risk register and asked for serious attention to this “catastrophic effect”. World Health Organization (WHO) has also highlighted the serious public health implications regarding antimicrobial resistance, in many resolutions. In 2001, the WHO global strategy for containment of antimicrobial resistance has provided a framework to emphasize the growing magnitude of antimicrobial resistance. In 2012, WHO published a detailed proposal entitled as, “the evolving threat of antimicrobial resistance-options for action”. This proposal mainly highlighted the importance of strengthened health surveillance system, infection control programs, development of new appropriate drugs, and a strong global commitment. The first World Health Organization (WHO) global report on surveillance of antimicrobial resistance (AMR), revealed in 2014, showed a significant extent of this evil phenomena all over the world, thus declaring antimicrobial resistance (AMR) as a major public health implication for 21st century. It respects no boundaries and indiscriminately ruining health paradigms. Therefore, globally coordinated actions, awareness campaigns and political commitments are need of the hour.

Antimicrobials are the most potent life-saving drugs. The reduction in the number of deaths are afforded by antibiotics. Studies have depicted that, the effective and timely availability of antibiotics has reduced the number of deaths from infections in the United States nearly by 80 percent, from 280 to 60 deaths per 100,000 population. The availability of antibiotics is imperative for advances in the modern medical establishments. They are of prime importance in a wide range of usage, from intensive care unit to aggressive surgeries, care of neonates, and chemotherapy as well. With losing the efficacy of antibiotics, medicine would have been paralyzed and it seems that we will be living back in the ages of stone.

Antimicrobial resistance-AMR is referred to the ability of a microbe to withstand the attack by antimicrobial drugs. When microbes develop resistance against antibiotics, infections are less likely to be treated. It may result into prolonged illness, increased mortality rates, economic burden, and several other complications. There are numerous ways by which a bacteria develops resistance against antibiotics. However, antimicrobial resistance is of two types: Intrinsic and acquired. Intrinsic resistance is the innate ability of a bacterium to resist a certain class of  antibiotics. It can be carried out by reduced permeability of the outer membrane-LPS and the natural activity of efflux pumps. On the flip side, acquired resistance can be ruled out in terms of genetic and biochemical mechanisms. Bacteria may mutate it’s genetic makeup or modify drug target sites, in order to survive the attack of antibiotics against them.

Factors contributing to the development and spread of antibiotic resistance are deeply rooted. It can be attributed to the increased community acquired resistance, ineffective infection control programs, increased international travelling, indiscriminate soaring misuse, over the counter availability of antimicrobials, irrational dose combination of antimicrobials, self-medication and substandard drugs causing sub-optimal blood concentration. Foreseeing the potential threat for antimicrobial resistance, in his Nobel Prize speech 1945, Alexander Fleming warned that,

“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 make them resistant.”            

Antimicrobial resistance can also be seen in the perspectives of one-health. Animals are essential to us in terms of food. The blind use of antibiotics in the therapeutics, prophylaxis and as a growth promoter is bearing us severe consequences. Drug residues in animal by products are stabbing concern. Improper administration of dosage or discontinued course of antibiotic treatment are major contributing factors in this regard. For overcoming this potent threat, proper awareness is needed. Farmers must learn the basics of antimicrobial resistance and antibiotic withdrawal period. Antibiotic withdrawal period refers to the mandatory time span required for an animal to metabolize an administered drug and to reach concentration of drug residues in tissues (meat/milk) at minimum or safer level. If this withdrawal period is not observed, drug residues in the meat/milk are perils to human health and thus, consumption of such animal by-products should be condemned.    

In Pakistan, the armageddon of antibiotic resistance have already prevailed. Studies have shown that developing countries like Pakistan, Afghanistan, India, Bangladesh, Uganda and Kenya have high level of antimicrobial resistance. Antibiotics are prescribed to nearly 7 percent patients here. Moreover, over the counter availability of antibiotics is an alarming concern. On the other hand, lack of education is a major hurdle. People in developing countries are habitual to self-medication and are thus more prone to irrational drug combination and overuse of the antimicrobials. This may have severe consequences for their individual as well as  community health. US Centre for Disease Control estimated that 23,000 Americans death per year is attributed to antibiotic resistance. The economic cost of such infections costs more than 20$ billion per year (CDC sources). This problem is soaring in developing nations with even greater magnitude, and if not stopped, future is awaiting us. This evil can surpass our economic potential and we may never be able to recover.

The COVID-19 is exacerbating the indiscriminate misuse of antibiotics. Some countries proclaimed the efficacy of azithromycin and hydroxychloroquine in COVID-19 despite no scientific approval.  Azithromycin overuse was observed during the spike of COVID-19 pandemic. This may lead to the complications in the treatment of significantly drug resistance typhoid (XDR) in Pakistan especially. Studies also have depicted the over prescription of antibiotics in case of telemedicine during pandemic. This malpractice should be properly address and prudent use of antibiotics must be discouraged. Overcrowding in hospital during the spike of pandemic, made a setback to the antimicrobial stewardship programmes.        

Considering the complexity of antimicrobial resistance, it can never be tackled by one scientific domain or even by research alone, but it needs collaborative approach and a strong commitment. In 2015, World Health Organization adopted a global action plan to combat antimicrobial resistance. The global action plan on antimicrobial resistance sets out five strategic objectives: 1. to improve the awareness and understanding of antimicrobial resistance; 2. to strengthen knowledge through surveillance and research; 3. to reduce the incidence of infection; 4. to optimize the use of antimicrobial agents; and 5. to ensure sustainable investment in countering antimicrobial resistance.  This way forward can be applied at international as well as national level.

Community engagement using a one-health approach can be significant to cope the wrath of antimicrobial resistance. Improve the awareness and understanding of antimicrobial resistance via training and education, improving national surveillance, carrying community based infection control programs, and appropriate and equitable use of antibiotics; can ensure commendable results. Legislative measures at national level can strictly monitor the use of antibiotics.

To put all in a nut shell, a comprehensive global as well as national plan is needed to combat the rage of antimicrobial resistance. The indiscriminate use of antimicrobials must be prohibited. Proper legislation in this regard, must be executed. Wits for the rational use of antimicrobials must exist.