BACKGROUND

The discovery of the world’s first antibiotic penicillin by Alexander Fleming is perhaps one of the most significant medical science milestones, for which he was awarded a Nobel Prize. The life-saving drug helped to save millions of patients suffering from pneumonia and blood infections globally. However, in 1945, Alexander Fleming had predicted that “The time may come when anyone in the shops can buy penicillin. 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.” He was right.  

Years of scientific research has yielded humankind many antibiotics to fight several lethal infections. However, most of these antibiotics have lost their efficacy or at the verge of becoming outdated due to rampant misuse.  At present antibiotic-resistance problem is the biggest threat to humanity that requires immediate attention. Evidence suggests that several common infections such as pneumonia, tuberculosis, gonorrhoea, and salmonellae are becoming increasingly harder to treat as the antibiotics used to treat them before are no longer effective. Without immediate action, antimicrobial resistance (AMR) is estimated to claim about 10 million lives every year by 2050, compared to 8.2 million by cancer and 1.5 million by diabetes, with the most significant impact in developing countries.

The consequences of antibiotic resistance are high, and there is every chance that we may enter the pre-antibiotic era. An integrated approach is required for managing antibiotic resistance along with a comprehensive antibiotic resistance review. The healthcare institutions, healthcare professionals, policymakers, and the public play a vital role in tackling this tip of the iceberg.  

CONSEQUENCES OF HIGH RESISTANCE RATES

There are both long-term and short-term effects of antibiotic resistance. Some of the impacts of antibiotic resistance are:

High Healthcare costs: Patients suffering from drug-resistant bacteria need to stay longer in the hospital. They may require costly antibiotics that increase the overall treatment cost. 

The emergence of more powerful pathogens: Unregulated use of antibiotics results in drug-resistant microbes. These microbes, in the further generation, emerges as more powerful pathogens.   

Increased mortality: Drug-resistance pathogens cause severe, life-threatening complications. It results in increased mortality rates. 

Relapse of infection: Antibiotic-resistant infections are more likely to relapse.

Increased spread of infection: Patient with drug-resistant infection carries the pathogens for a prolonged period. Thus, there is a high risk of transmission. 

Severe side effects: Patients with drug-resistant infections require aggressive treatment. It may result in severe side effects, especially related to the liver and kidney. 

DRYING ANTIBIOTICS PIPELINE

The World Health Organization released a news alert about the global danger of drug-resistant infections on 17 January 2020. The pipeline for new antibiotics has slowed to a trickle, and bankruptcies have driven pharmaceutical giants out of the market. Two recent studies show a shortage of antibiotic agents in the pipeline. The 60 drugs in production (50 antibiotics and 10 biologics) provide a slight advantage over conventional therapies, and only a handful attack the most dangerous resistant bacteria (Gram-negative bacteria).

Though pre-clinical candidates (those in the early stages of testing) are more innovative, they will not be reaching the patients for years.

“We urgently need research and development,” said Sarah Paulin, technical officer of Antimicrobial Resistance and Innovation at the W.H.O. and an author of two reports on the subject issued Friday. “We still have a window of opportunity, but we need to ensure there is an investment now, so we don’t run out of options for future generations.”

PRE- AND POST-ANTIBIOTIC ERA: A COMPARATIVE ANALYSIS

A bacterial infection took the life of 70-year-old women in the United States recently. Reason? The infection was resistant to 26 antibiotics. This rise in dangerous resistance makes us think that are we heading towards a pre-antibiotic era.

There were no antibiotics in the pre-antibiotic era. Bacterial infections severely affected both adults and children. The mortality rates due to these infections were significantly high. Death due to bacterial meningitis was as common as 90% in children. Those who survived had significant physical and mental disabilities. Strep throat, considered a typical infection today, was life-threatening in the pre-antibiotic era.

• The antibiotic era initiated with the discovery of Penicillin in 1928. After that, pharmacists developed several antibiotics to manage various types of infections. 
• Gerhard Domagk was the pioneer in developing sulfonamides that helped prevent infection during the second world war. 
• Selman Waksman, in 1944, discovered a series of antibiotics, including actinomycin, streptomycin, and neomycin. He received the Noble Prize for discovering streptomycin.  The pharma companies and scientists discovered several novel classes of antibiotics between the 1950s and 1970s, which is probably the golden era of antibiotic development. 

WHAT GLOBAL RESISTANCE DATA CONCLUDES?

Antibiotic-resistant bacteria are emerging at a rapid rate. The global antibiotic resistance market was over 7 billion in 2017 and is estimated to increase at a CAGR of 5.6% between 2018 and 2025. This market's growth is majorly fueled by an increase in the incidences of antibiotic-resistant infections and the drying pipeline of antibiotics. The trend of antibiotic resistance has been witnessed globally. More than 58000 babies in India died in a year due to resistant infection from the mothers. Antibiotic resistance claimed the lives of over 25,000 people annually due to antibiotic resistance, with 2.5 million excess hospital days. 

Data collected between 2007-2011 indicated that MRSA obtained from Sikkim was resistant to 38% of the standard antibiotics, while 92% of Staphylococcus aureus obtained from Mangalore were resistant to penicillin, and 31% were resistant to erythromycin.

To tackle the growing menace, the World Health Organization (WHO) in May 2105 has developed and adopted a Global AMR action plan. The plan has the following five objectives:

• Increasing awareness about antibiotic resistance.
• Incorporating surveillance and research for strengthening knowledge.
• Reduce the occurrence of infection.
• Optimize and logical use of antimicrobials.
• Develop a financial plan for pharmaceutical research and development to boost new antibiotics, vaccines, and innovative diagnostic methods.

ADDRESSING ANTIBIOTIC RESISTANCE: ONUS OF THE HEALTHCARE PROFESSIONALS

Rampant prescription of antibiotics coupled with self-medication contributes to the emergence of antibiotic resistance. For example, the extensive use of vancomycin led to the development of vancomycin-resistant enterococci. Some of the other antibiotic resistance bacteria examples include imipenem-resistant Acinetobacter baumannii and multidrug-resistant (MDR) Pseudomonas aeruginosa.

Evidence suggests that antibiotic overprescribing for a viral infection is expected in a primary care setting, accounting for about 90% of all antibiotic prescription. Respiratory tract infections being the leading cause of antibiotic misuse. Lower antibiotic use appears to be one of the key strategies to prevent antibiotic resistance. Some of the essential interventions should include

• Prohibiting the over-the-counter sale of antibiotics
• Development of Antimicrobial Stewardship Programs that guide the use of antimicrobial therapy
• Promotion of delayed antibiotic prescribing strategies. All healthcare workers should be adequately trained when to use antibiotics. This particular strategy will limit the use of antibiotics. 
• There should be better and fast sampling and analysis methods to prolong empirical therapy. Ruling out infection as early as possible helps in avoiding the unnecessary use of antibiotics. 
• There should be policies in place in the hospital regarding the use of antibiotics. Every healthcare worker should understand antibiotic resistance meaning. There should be monitoring and audit of antibiotic prescription in the healthcare settings. 
• Patient education on rational antibiotic use and resistance  There are various causes of antimicrobial resistance, and the following are some crucial steps to avoid them. Prevention is always better than cure. Stopping the spread of infection itself cuts down the risk of falling sick and the need for antibiotics
• The hospital and health workers should follow proper sanitization methods to prevent nosocomial infections. 
• Proper hygiene, such as hand hygiene, significantly reduces the risk of upper and lower respiratory tract infections and diarrhoea. 

REFERENCES

• World Health Organization. Lack of new antibiotics threatens global efforts to contain drug-resistant infections. Available at: https://www.who.int/news/item/17-01-2020-lack-of-new-antibiotics-threatens-global-efforts-to-contain-drug-resistant-infections. Accessed on 19th February 2021.
• Center for Infectious Disease Research and Policy. The analysis highlights troubles in the antibiotic pipeline. Available at: https://www.cidrap.umn.edu/news-perspective/2020/04/analysis-highlights-troubles-antibiotic-pipeline. Accessed on 19th February 2021.
• World Health Organization. Antibiotic Resistance. Available at: https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance. Accessed on: 19th February 2021.
• World Health Organization. Global action plan on antimicrobial resistance. Available at: https://www.who.int/antimicrobial-resistance/global-action-plan/en/. Accessed on: 19th February 2021.
• Lee CR, Cho IH, Jeong BC, Lee SH. Strategies to minimize antibiotic resistance. Int J Environ Res Public Health. 2013;10(9):4274-4305. Published 2013 Sep 12. doi:10.3390/ijerph10094274
• World Health Organization. Antimicrobial resistance: global burden. https://www.who.int/medicines/technical_briefing/tbs/TBS2016_AMR_GAP.pdf. Accessed on: 19th February 2021.
• Llor C, Bjerrum L. Antimicrobial resistance: risk associated with antibiotic overuse and initiatives to reduce the problem. Ther Adv Drug Saf. 2014;5(6):229-241.
• Center for Disease Control and Prevention. Info-graphic: Antibiotic Resistance The Global Threat Available at https://www.cdc.gov/globalhealth/infographics/antibiotic-resistance/antibiotic_resistance_global_threat.htm. Accessed on 21st February 2021.
• Mint. The perils of irrational antibiotic use. Available at: https://www.livemint.com/Politics/rQUHZ98ogyXrkdHYvjS0uI/The-perils-of-irrational-antibiotic-use.html. Accessed on 21st February 2021
• Andrew Jacobs. W.H.O warns that the pipeline for new antibiotics is running dry at: https://www.nytimes.com/2020/01/17/health/antibiotics-resistance-new-drugs.html. Accessed on 12th April 2021

FAQs

1. What are the risks associated with the overuse of antibiotics?

There are various risks associated with antibiotic overuse. These are increased bacterial resistance towards antibiotics, severe infections, complications and an increased hospital stay. These challenges faced with the hospital stay will increase the overall healthcare cost. 

2. What role does a policymaker play in preventing antibiotic resistance?

A comprehensive approach, from all the sections, is required to curb the menace of antibiotic resistance. The policymakers should make policies that reduce unnecessary antibiotic prescription and prevent the spread of infections. They should improve surveillance and make the people aware of the consequences of antibiotic resistance.

3. What is the World Antimicrobial Awareness Week?

World Health Organisation (WHO) started antimicrobial awareness week in 2015. The awareness week's primary aim is to increase awareness about the impact of antibiotic resistance on healthcare. It also aims to emphasize the best practices that people and healthcare workers should follow to reduce antibiotic resistance.

4. Can you reverse the antibiotic resistance?

It will depend upon whether the resistance is permanent or temporary. If the resistance is temporary, then there are chances that the resistance may be reversed. However, if the resistance is permanent, chances are remote to get them reversed. The only way to reduce antibiotic resistance in the long term is to reduce dependency on them. 

5. How common is irrational antibiotic use in India?

Several antibiotic combinations are available in the Indian market. Many of them are without proper clinical trial and the approval of a regulatory body. Approximately 70-80% of the antibiotic prescriptions in India are prescribed without any necessity. Overprescribing of antibiotics by healthcare providers, over-the-counter sale of antibiotics, and self-medication potentially increase the risk of antibiotic resistance.