Former Director OPPI( Project & Policy) |
Former GSK (Sales, Marketing & Training) |
Email: vmpadgaonkar@yahoo.co.in |
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- Antibiotic Resistance Crisis in India and Role of Government - November 20, 2023
Last Updated on March 8, 2024 by The Health Master
Preamble
Antibiotic resistance is intrinsically linked to animal and human consumption patterns, partly driven by inappropriate use of antibiotics. In turn, the emergence of antibiotic resistance fuels changes in consumption patterns, as more costly broad-spectrum antibiotics become required to manage even common conditions.
India is the largest consumer of antibiotics globally in terms of absolute volume. Various research studies from India have reported poor prescription quality, including unindicated prescription of broad-spectrum antibiotics without evidence of bacterial infection. These findings are of particular public health relevance considering that India reports high antibiotic resistance in bacteria that cause certain common infections.
Wide variations exist between Indian states in terms of their population age structure, health-seeking behaviour, infectious disease burden, health systems organization and the relative contribution of the public and private sector in healthcare
The rapid emergence of resistant bacteria is occurring worldwide, endangering the efficacy of antibiotics, which have transformed medicine and saved millions of lives. Many decades after the first patients were treated with antibiotics, bacterial infections have again become a threat.
The antibiotic resistance crisis has been attributed to the abuse, overuse and misuse of these medications, as well as a lack of new drug development by the pharmaceutical industry due to reduced economic incentives and challenging regulatory requirements.
In Asia, infectious diseases make up a substantial 40% of the total disease burden. This includes formidable illnesses like Malaria, Tuberculosis (TB), and Human Immunodeficiency Virus (HIV), which necessitate treatment with antibiotics. Unfortunately, in India, there is a lack of a robust surveillance system.
When it comes to Malaria, the conventional treatment with Chloroquine has proven ineffective, thereby requiring the use of more costly artemisinin derivatives. Shockingly, 28% of TB cases in the region are classified as Multi-Drug Resistant (MDR) TB. Moreover, the second-line therapy for managing HIV is six times more expensive. This not only makes the fight against these diseases more challenging, but it also significantly escalates the associated costs.
In a recent study conducted by the Indian Council of Medical Research (ICMR), concerning revelations about Antibiotic resistance have emerged, painting a grim picture of healthcare in India. The abuse and overuse of antimicrobials, including antibiotics, antivirals, and antifungals, have led to widespread resistance to these drugs within the community
The battle against antibiotic resistance is a critical one, demanding a collective effort from healthcare professionals, researchers, and policymakers alike.
Also read: Understanding the Alarming Rise of Antibiotic Resistance in India
Antibiotic Development
Antibiotic development is no longer considered to be an economically wise investment for the pharmaceutical industry. Because antibiotics are used for relatively short periods and are often curative, antibiotics are not as profitable as drugs that treat chronic conditions, such as cardiac, diabetes, psychiatric disorders, asthma, or gastroesophageal reflux.
A cost–benefit analysis by the Office of Health Economics in London calculated that the net present value (NPV) of a new antibiotic is only about $50 million, compared to approximately $1 billion for a drug used to treat a neuromuscular disease. Because medicines for chronic conditions are more profitable, pharmaceutical companies prefer to invest in them.
Over the span of 80 years, a total of 150 antibiotics have been developed. However, it is not anticipated that any new antibiotics will be introduced for a minimum of 10 years.
Because of these factors, many large pharmaceutical companies fear a potential lack of return on the investment that would be required to develop a new antibiotic. The Infectious Diseases Society of America (IDSA) reported that as of 2013, a very few antibacterial compounds were in phase 2 or 3 development.
Co-trimoxazole Clinical Effectiveness
Clinical Effectiveness comparison of co-trimoxazole versus leading antibiotic molecules and against leading diseases conclusively prove that this most economical molecule ie Co-trimoxazole is considered as the antimicrobial agent of choice in the treatment of many diseases, minimizing the risk of vital organ involvement and relapses and is superior or equal to many molecules that are prescribed in the country.
Price comparison : Therapeutic Substitutes in Antibiotics
In India, the out of pocket expenditure constitutes ~60% of total health expenditure with substantial 40% being incurred on the medicines (Ref : Report of Standing National Committee on medicine SNCM 2022). With this background it is of paramount importance that the accessibility & availability of essential medicines be enhanced in order to reduce the financial burden.
The National List of Essential Medicines (NLEM) of the Ministry of Health & Family Welfare (MHFW) is incorporated in the Schedule-I of the Drugs (Prices Control) Order, 2013 (DPCO, 2013). The formulations under Schedule-I of DPCO, 2013 are mentioned according to their therapeutic category.
Also read: Antibiotic resistance: Read this before taking any medications
There is no separate classification of antibiotics based on the generations i.e., 3rd or 4th generation Antibiotics. However, the Section 6.2 of Schedule-I of DPCO, 2013 deals with the class, “Antibacterials”, which includes 95 formulations of 27 medicines. Out of these, ceiling prices for 74 formulations have been fixed under NLEM 2022 and 11 formulations under NLEM 2015 as on 31.07.2023 by National Pharmaceutical Pricing Authority (NPPA).
Prices of other molecules which are used as therapeutic substitutes for the bacterial infections in case of non-availability of Co trimoxazole. (Trimethoprim 80 mg)+Sulfamethoxazole 400 mg ) tabs
| Molecule | Price per tab excluding GST (March 2022) | Source |
| Amoxicillin 500 mg + Clavulanic Acid 125 mg Tabs | 19.95 | NPPA S.O. 1499(E) 30th March 2022 |
| Azithromycin 250 mg Tabs | 11.72 | |
| Cefixime 200 mg Tabs | 10.66 | |
| Amoxicillin 500 mg Caps | 7.17 | |
| Levofloxacin 250 mg Tabs | 4.90 | |
| Cefadroxil 500 mg Tabs | 4.47 | |
| Ciprofloxacin 250 mg Tabs | 2.30 | |
| Co-trimoxazole (Trimethoprim 80 mg)+Sulfamethoxazole 400 mg ) tabs Tabs | 0.86 | NPPA S.O. 1499(E) 30th March 2022 |
………“A considerable price difference was observed between brands of a particular generic formulation marketed by different firms. To illustrate, one of the top selling formulations in the antibiotic category, namely, amoxicillin + clavulanic acid (Tablet, 125/500 mg), is currently sold by 217 companies under 292 brands. Substantial price variation was observed between companies selling different brands, ranging from Rs. 40 to Rs. 336 for a pack of six tablets.”………
…..“The price difference for antibiotics was in the range of 82–193%”…….
Source: CCI Report market-study-on-the-pharmaceutical-sector-in-India
As evidenced by the data, despite the seemingly strong generic competition, gauged in terms of the number of players present in each of the therapeutic areas and at the level of formulations/molecules, consumers in India ostensibly pay a premium for brands.
…..The substantially large price variations amongst various brands catering in the same therapeutic areas.( CCI Nov 18, 2021.. mentions about the same formulations)
| Anti-infective therapy Penetration | |||
| Therapy Area | No. of Formulations | No. of Brands | No. of Brands Per Formulation |
| Anti-Infective | 290 | 5349 | 18 |
……The average number of brands per formulation across therapy areas hides the stark variation observed within each formulation. In fact, the number of brands varies considerably even between different strengths and doses…….
Price Comparison : Single Strength vs Double Strength formulations in Antibiotics
| Molecule (Tablets) | 2014 | 2015 | 2016 | 2017 | 2018 | 2019 | 2020 | 2021 | 2022 | 2023 |
| Ciprofloxacin 500 mg | 4.01 | 3.9 | 3.23 | 3.42 | 3.57 | 3.64 | 3.66 | 4.05 | 4.24 | |
| Ciprofloxacin 250 mg | 2.1 | 2.27 | 1.58 | 1.95 | 2.03 | 2.07 | 2.08 | 2.3 | 2.19 | |
| Ratio | 52% | 58% | 49% | 57% | 57% | 57% | 57% | 57% | 52% | |
| Levofloxacin 500 mg | 6.09 | 7.57 | 7.89 | 8.04 | 8.08 | 8.95 | 8.80 | |||
| Levofloxacin 250 mg | 4.00 | 4.14 | 4.32 | 4.40 | 4.42 | 4.9 | 4.76 | |||
| Ratio | 66% | 55% | 55% | 55% | 55% | 55% | 54% | |||
| Cotrimaxazole 800/160 | 1.28 | 1.37 | 1.33 | 0.96 | 0.99 | 1.32 | 2.02 | 2.03 | 2.25 | 2.52 |
| Cotrimaxazole 400/80 | 0.58 | 0.6 | 0.62 | 0.47 | 0.49 | 0.51 | 0.78 | 0.78 | 0.86 | 0.89 |
| Ratio | 45% | 47% | 49% | 49% | 39% | 39% | 38% | 38% | 35% |
The difference in costing of the single strength and double strength is usually attributed to the quantum of API, whereas the rest of the cost components such as excipients and packaging costs are similar, therefore in terms of costing, the cost of single strength is usually more than 50% of double strength.
Also read: Antibiotic abuse causing drug resistance: Experts
Similar difference can be observed in the prices in the above table which clearly exemplifies that the ratio of the price of single strength as a percentage of double strength is over 50% for anti biotics like levofloxacin and Ciprofloxocin, whereas for cotrimoxozole it is as low as 35%.
The relatively larger number of brands are typically present in markets with a larger number of formulations. In some therapy areas, the number of brands created are disproportionately larger than the number of formulations.
The market failure (non-availability of medicines in the market) in respect of pharmaceuticals in the context of India can be attributed to several factors, but the main reason is that the demand for medicines is largely prescription driven and the patient has very little choice in this regard. The sales promotion drives doctors’ prescriptions. The sales promotion budget is a function of the revenue generated by the brand.
Co-trimoxazole (Trimethoprim 80 mg + Sulfamethoxazole 400 mg ) tabs proved to be significantly lower in price to the patients, with fewer options than any of the above mentioned therapeutic substitutes for the patients suffering from the bacterial infections.
Unfortunately if the financial unviability continues companies marketing Co-trimoxazole may be left with no option but to exit from this category leaving ailing patients for much costly exploitative options.
Research study on Health Care Professionals (HCPs) in India
In a latest research study which was conducted amongst 763 HCPs across India including Metros and Class I, II towns & beyond. 100% of the HCPs opined that AMR is something that they are aware with in their clinical practice. Medical practitioners recognized that AMR is a global health threat & poses a significant challenge to their ability to treat infections effectively, which can lead to higher mortality rates and longer hospital stays.
In the 1436 Bills from the chemists shops across the country analysed in the another research study, it was observed that patients buy some antibiotic or the other, in 63% there was one or more antibiotic present.
Also read: Resistance to common antibiotic rising among Indian patients
One of the medical practitioners mentioned that “Antibiotics are less effective when used repeatedly and without any control. We have seen more than 50% of cases wherein repeated usage of Antibiotics have resulted in AMR in our patients and we are very concerned with the same in India.”
On a Query asked that whetherthey feel pressured to prescribe antibiotics even when they suspect they may not be necessary? HCPs mentioned that patient pressurises them to write an antibiotic as they feel that the antibiotic will provide a quick relief and they can get back to work faster. The medical practitioners said that they believe in the importance of educating patients about antibiotic & they spend time explaining to their patients when antibiotics are necessary and when they are not.
When Pronto Consult conducted a research study amongst 456 chemist shops on the key question of “ How often do you encounter patients requesting antibiotics for conditions that do not typically require them ?” Almost 73% of the chemists mentioned that the patient directly asks them an antibiotic and want to buy. Most of them don’t have a doctor’s prescription and want to buy an antibiotic,may be a formulation of Amoxy-Clav, Azithromycin or a Cefixime.
Pronto Consult also spoke with 874 consumers ontheir awareness of Anti-microbial Resistance. 71% were not aware about AMR.29% mentioned they have heard or read in the news. This is a serious concern which needs to be addressed by proper education and needs to be taken up by all stakeholders.
On a Question to consumers that “ Do you pop an antibiotic every time when you are ill?” 81% mentioned they have taken antibiotic most of the time they have fallen ill and 71% stop the medicine as soon as they feel fine without completing the full prescribed course of the antibiotic.
Also read: Antimicrobial Resistance in India: The Alarming Rise and Potential Solutions – ICMR
Dr Karishma Shah, Founder Pronto Consult comments that “doctors generally view AMR as a complex and critical issue that requires a multifaceted approach, including responsible antibiotic prescribing, patient education, research, and collaboration among healthcare professionals and policymakers to combat this growing threat to public health.”
Karishma adds that “Antimicrobial Resistance reminds us that in the battle between man and microbe, adaptability is the true measure of strength. It’s a call to action for responsible stewardship of antibiotics and the pursuit of innovative solutions, as our survival depends on the wisdom to evolve with the ever-changing microbial world.”
Government’s initiatives on anti-microbial resistance (AMR)
The Government has taken the cognizance of the increasing issue of Antimicrobial Resistance (AMR) which can be one of the public health crises in coming years and has taken the following initiatives have been planned to prevent the increasing risk of AMR;
The Government is planning to expand and diversify the AMR National Action Plans (NAPs) with the robust surveillance systems will be followed in the hospitals to facilitate early detection of AMR
Government is aware about the challenges posed by anti-microbial resistance (AMR) in India. It is a multifaceted problem with significant consequences for individuals as well as Health Care Systems.
To capture the trends and pattern of AMR in India, ICMR has established an AMR surveillance and research network (AMRSN) to monitor data on the trends and patterns of antimicrobial resistance of clinically important bacteria and fungi limited to human health from 30 tertiary hospitals. MoH&FW has taken several steps to address the issue of AMR. Some of the steps are:
- AMR surveillance network has been strengthened by establishing labs in State Medical Colleges. 38 sites in 30 States/UTs have been included in this network so far.
- National action plan on containment of Antimicrobial Resistance (NAP-AMR) focusing on One Health approach was launched in April 2017 with the aim of involving various stakeholder ministries/ departments. Delhi Declaration on AMR– an interministerial consensus was signed by the ministers of the concerned ministries pledging their support in AMR containment.
- AMR Surveillance Network: ICMR has established AMR surveillance and research network (AMRSN) comprising 30 tertiary care hospitals, both private and government to generate evidence and capture trends and patterns of drug resistant infections in the country.
- AMR Research & International Collaboration: ICMR has taken initiatives to develop new drugs / medicines through international collaborations in order to strengthen medical research in AMR. Further, to create awareness IEC materials including audios, videos, social media messages and Outdoor Media has developed and is also shared with states for further dissemination. MoHFW has released National Guidelines for Infection Prevention and Control in Healthcare Facilities in Jan 2020.
National Center for Disease Control under MoHFW is conducting several stakeholder consultations to monitor the implementation of existing National action plan on AMR by various department and ministries. The consultations are also to guide the development of a more practical and implementable National action plan on AMR 2.0.
Under the National Programme on AMR Containment, 38 state medical colleges/large Government hospitals in 30 states/UTs have been strengthened to do AMR surveillance on 7 priority pathogens. These sites have robust surveillance systems to facilitate early detection on AMR. AMR emerging alerts are also confirmed at the National Reference Laboratory.
Anti-Microbial Resistance (AMR) discussed in Loksabha
Union Health Ministry has taken several initiatives to spread awareness about appropriate use of antibiotics and control AMR which include:
- Red line campaign was launched to curb over the counter sale of antibiotics.
- Antibiotics Stewardship Program(AMSP) has been implemented in 20 tertiary care hospitals to control misuse and overuse of antibiotics in hospitals wards and ICUs.
- National Action Plan on AMR has been launched in 2017 with an objective of intersectoral coordination, improve awareness, strengthening knowledge and evidence through surveillance of AMR, reduce incidence of infection through effective infection prevention and control and promote optimal usage of antibiotics.
- Issued guideline for Antimicrobial use in common syndrome in 2019.
- Developed guidelines on Infection Prevention and Control in 2020.
- Guidelines for management of carbapenem resistant have been developed in 2022.
- With an aim to regulate sale of antibiotics, it has been included in Schedule H and H1 of the Drugs Rules,
- 1945 and are required to be sold by retail only under the prescription of a Registered Medical Practitioner. State
- Licensing Authorities are empowered to take action against any violation. The State Drugs Controllers/other stake holders have been sensitized in this regards.
- Various Notices/Advisories /Letters have been issued to all State Drugs Controllers, other stakeholders for strict compliance of the requirements of Drugs and Cosmetics Act and Rules.
Source : Lok Sabha Unstarred Question No. 4894;Dr. M.P. Abdussamad Samadani:
Summary
The impact of loss of antibiotic efficacy due to emergence of drug-resistance in various bacterial pathogens is creating a ´silent pandemic’.
Antimicrobial resistance (AMR) poses a substantial threat to humanity, with the potential to render some of our most innovative medicines ineffective against common infections that for decades, and in some cases over a century, have been easily managed with antibiotics.
With the potential for AMR to push 28 million people into poverty and 10 million deaths/year by 2050 (especially in countries), the time to invest in solutions is now. As per latest estimates for year 2021, AMR related deaths were already more than 4 million.
The global response does not match the scale of the problem. The market for new antibiotics is nearly non-existent and, as a result, more than 82% of all antibiotic approvals occurred prior to the year 2000.
The Hon’ble Supreme Court of India vide Order dated 12.11.2002 in SLP no. 3668/2003 (Union of India vs K.S. Gopinath & others) has directed the Government to ensure that essential and life saving drugs should be available & affordable to the common public.
the market failure alone may not constitute sufficient grounds for government intervention, but when such failure is considered in the context of the essential role of pharmaceuticals play in the area of public health, which is a social right, such intervention becomes necessary, especially when exploitative pricing for the therapeutic substitutes makes medicines unaffordable and beyond the reach of most and also puts huge financial burden in terms of out-of-pocket expenditure on healthcare.
The continuous price control has led to financial unviability of therefore causing an erosion in the value of Co-trimoxazole (Trimethoprim 80 mg+ Sulfamethoxazole 400 mg)tab from 2013 to 2023 ~ 84 % erosion of value.
Conclusion
The government should make the availability of drugs at affordable prices, while ensuring affordability, accessibility cannot be jeopardized and the lifesaving essential medicines must remain available to the general public at all times.
Therefore, it is important for the government to take the considered view that the financial unviability of these formulations -Co-trimoxazole (Trimethoprim 80 mg+ Sulfamethoxazole 400 mg) tablets should not lead to a situation, where these drugs become unavailable in the market and the ailing patients are forced unfortunately to switch to very costly alternatives and therapeutic substitutes heavily promoted from the non-scheduled formulations category.
In final words “Antimicrobial Resistance is a silent pandemic, a reminder that our actions today shape the future of medicine. To preserve the power of antibiotics, we must act responsibly and collectively, for a world where infections remain treatable and lives are safeguarded.”
Authors:
Prof. Vivek Padgaonkar : Former Director OPPI
Dr Hari Natarajan: Founder & Managing Partner Pronto Consult
Disclaimer: The views expressed are solely those of the authors, and TheHealthMaster.com does not necessarily subscribe to them. TheHealthMaster.com shall not be responsible for any damage caused to any person / organization, directly or indirectly.
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