The index mapping the ineffectiveness of antibiotic therapy of any nation is higher in developing countries, such as India. The lack of adequate healthcare facilities, clean environmental conditions, insufficient availability of standard infection prevention and control items seems alarming. Further, illiteracy, poverty, overcrowding, and malnutrition in India compound the situation. Moreover,

• India ranks among one of the top countries globally in antibiotic consumption
• Lack of policies in place to halt the supply of ‘over the counter drugs’
• Pluralistic health care system in India
• The trend of self-medication or use of leftover drugs
• The massive use of antibiotics in animals and aquaculture as growth promoters
• Unsafe disposal of pharmaceutical waste and hospital effluents in water
• The dearth of platforms creating awareness on AMR in society
• Absence of projects in Asia tackling AMR at grass-root levels
• The dearth of compulsory curriculum/ free online courses creating awareness on risk management and prevention of ABR
• Lack of research and India-based specific publications on AMR

High population density, poor hygiene practices and unorganized healthcare facilities are common factors contributing to ABR in India. In addition, human behavior (at consumer/prescriber level), medical tourism fuel the rate of the development of ABR. Moreover, India is the 1st largest producer of milk and the 5th largest producer of meat. Antibiotics are used in animal health as prophylactic, growth promoters and as a medicine. It is estimated that total antibiotic consumption only in the poultry sector of India will rise by 312% by 2030. Furthermore, antibiotic-resistant bacteria, antibiotic resistance genes, antibiotic residues transfer to the environment and the vicious cycle of AMR transmission continues.

A study led by the AMR surveillance network in India revealed high levels of resistance to antibiotics among various bacteria isolated from hospitals, humans, animals, animal products and other food items, water bodies, soil. Bacteria have acquired resistance to not only first-line antibiotics but also to third-generation antibiotics. Some major antibiotics resistant bacteria are Staphylococcus aureus, Carbapenem-resistant Enterobacteriaceae (Escherichia coli, Klebsiella, Shigella, Vibrio and Salmonella), Acinetobacter baumannii, Neisseria gonorrhoea and Mycobacterium tuberculosis. To read more about the AMR situation in India: Click here

Antimicrobial resistance (AMR) has been identified as a global health threat with serious health, political and economic implications. From the year 1998 onwards, AMR was given due importance across various World health assembly resolutions, United Nations general assemblies as well as the regional committee's resolutions. In May 2014, the Sixty-seventh World Health Assembly adopted resolution WHA67.25 on antimicrobial resistance, in which it requested to develop a draft global action plan to combat antimicrobial resistance. The Global Action Plan paved the way for the development of various national-level action plans taking into account the diversity across the countries.

The overall goal of GAP AMR

The overall goal of the action plan is to ensure, for as long as possible, continuity of the ability to treat and prevent infectious diseases with effective and safe medicines that are quality-assured, used responsibly, and accessible to all who need them. Five strategic objectives have been made to proceed to the goal:

In order to fulfil the strategic objectives, collaborative actions are necessary through stakeholder engagement, funding sources, technical experts, situation analysis and proper guidelines. These are necessary to implement planned global actions, develop and implement national action plans and conduct research and development. The various outputs of these activities would help in achieving the proposed strategic objectives.

Finally, it is expected that these would lead to reduced levels of resistance development, thereby facilitating the healthcare system to continue treating infectious diseases effectively and safely.

For more details, click: Global Action Plan on Antimicrobial Resistance

Challenges

While there is no doubt that GAP-AMR is a well-thought plan with an impressive number of more than 120 countries already developed their National Action Plans, the question arises on how well these Plans have aligned to the GAP-AMR which could influence the global governance of AMR. A study by Louise Munkholm & Olivier Rubin found that most of the National Plans developed were very similar in outline and content (including objectives and actions) to the GAP. But, the actual implementation and monitoring of these NAPs were highly questionable. The article pointed out that the subjective assessment of the alignment of NAPs to GAP has been made through the Global Database for Antimicrobial Resistance Country Self-Assessment, which has its own pitfalls. This includes subjective interpretations of the survey questions, lack of validation, transparency issues, mistakes due to manual entry, and moreover, the survey has limitations to identify the alignment of NAPs to the GAP. The survey has a very limited number of questions dealing with objectives 3,4 and 5 of GAP AMR.

The absence of a comparable dataset on AMR policies complicates the matter further. At present, GLASS (Global Antimicrobial Resistance and Use Surveillance System) comes close to such a dataset. But the catch is, only 87 countries are enrolled and the system also follows self-reporting. There is a clear lack of objective methods for measuring the alignment of NAPs to GAP AMR. As rightly mentioned in the article: “Global governance should not be perceived as two separate processes where the WHO designs universal policy guidelines and then leaves it to regional WHO offices and national governments to implement them. The fact that we see this disconnect between policy documents and actual practices indicates the need for addressing the policy process as a whole rather than reducing the challenge to one of policy implementation.” Another article by Arne Ruckert points out that GAP is not a “binding governance mechanism” wherein the signatories are legally held responsible and accountable. Hence, many countries fail to voluntarily adhere to the GAP AMR. The member states are also facing difficulties in identifying resources to develop and implement the NAP in alignment with GAP.

As long as the spread of antibiotic resistance differs among developed countries and developing countries, national governments should take action to elaborate strategies related to their country’s needs, in line with the solutions drafted by the Global Action Plan. In fact, while the developed countries face antibiotic misuse in animal farming and agriculture, the developing countries are misusing antibiotics due to a lack of qualified health personnel. Moreover, developed countries are providing a low amount of aid towards ABR control activities, while the developing countries are struggling to allocate enough resources towards ABR activities. Hence, governments have a critical role to play to curb the spread of antibiotic-resistant infections. They have a wide variety of policies at their disposal for the same.

India is among the nations with the highest burden of bacterial infections. AMR is a major public health concern in India. The resistance to newer and more expensive drugs has been recorded in addition to the commonly used antibiotics. Accepting the call of the World Health Assembly for developing the country-specific National Action Plan, India developed the National Action Plan on Antimicrobial Resistance. The goals of the Indian NAP-AMR are:

• To effectively combat antimicrobial resistance in India, and contribute towards the global efforts to tackle this public health threat
• To establish and strengthen governance mechanisms as well as the capacity of all stakeholders to reduce the impact of AMR in India.

The objectives of the National Action Plan:

• Define the strategic priorities, key actions, outputs, responsibilities, and indicative timeline and budget to slow the emergence of AMR in India and strengthen the organizational & management structures to ensure intra- & inter-sectoral coordination with a One Health approach;
• Combat AMR in India through better understanding and awareness of AMR, strengthened surveillance, prevention of emergence and spread of resistant bacteria through infection prevention and control; optimized use of antibiotics in all sectors, and enhanced investments for AMR activities, research, and innovations;
• Enable monitoring and evaluation (M&E) of the NAP-AMR implementation.

Challenges

India’s National Plan is well aligned to the Global Action Plan and aptly includes the one health approach theoretically. As per the self-assessment survey 2019-2020, India reports that human health, animal health, food safety and environment sectors are actively involved in developing and implementing the AMR NAP while information about plant health and food production sectors are missing. Considering the one health aspect, though multi-sectoral working groups are functional, bringing together various stakeholders to a common objective is still a challenge for India. The actual implementation of NAP on the ground is rather slow as per the article by Jaya Ranjalkar and Sujith J. Chandy. Lack of separate financial allocation is the major obstacle to the proper implementation of NAP-AMR in India. Further, the absence of strong political commitment and public-private partnership support has also contributed. Looking into the gaps within the NAP-AMR document, the authors point out that, considering strategic priority 1, there is a need to include mass media campaigns especially for awareness on AMR. Additionally, culture and context-specific behavior change strategies also need to be incorporated into the NAP-AMR. In the AMR self-assessment survey 2019-2020, India reports that only a limited number of antimicrobial resistance awareness campaigns targeting some stakeholders on human health have been carried out. Animal health, environment and food safety sectors didn’t get adequate attention for the same, while the plant health and food production sectors were totally left out of all the educational and awareness activities.

Talking about the training and professional education on AMR, AMR is covered in some pre- and in-service training or other continuing professional development (CPD) for human health workers. In the veterinary sector, AMR and prudent use of antimicrobial agents are covered in the core curricula for graduating veterinarians and for veterinary paraprofessionals in some educational institutions. There are no training provisions on AMR for key stakeholders, e.g. farmers, extension workers, food and feed processors and for retailers and environmental specialists in the farming sector (animal and plant), food production, food safety. Considering strategic priority 2, though India has a Surveillance network for AMR, it needs to be expanded nationally. In order to do so, there is a need to improve the quality of laboratories, availability and training of the lab personnel, as well as infrastructures and quality checks. Under strategic priority 3, India has a program specifically designed to undertake the task. Though national IPC (Infection, prevention, control) and water, sanitation and hygiene (WASH), environmental health standards exist, they are not fully implemented in the human health care sector. The authors suggest that in addition to the existing IPC guidelines, the IPC can be ensured only if the program will be made mandatory for licensing/accreditation of health care institutions. Some activities are in place to develop and promote good health, management and hygiene practices to reduce the use of antimicrobials and minimize the development and transmission of AMR in animal production (terrestrial and aquatic). But a national-level program and guidelines are absent. No activities are undertaken to optimize antimicrobial pesticide use (including bactericides and fungicides) in plant production. Under strategic priority 4, though many regulations are in place for optimum antibiotic use, the country has no legislation on the marketing of pesticides including antimicrobial pesticides, such as bactericides and fungicides used in plant production. The 29 states in India must come together by developing and implementing the respective state action plans to combat AMR. Unfortunately, only 3 states (Kerala, Delhi and Madhya Pradesh) have developed their state action plans, even after 4 years of implementation of the NAP-AMR.

Surveillance plays a crucial role in monitoring and evaluating the trends of emerging diseases. It is crucial for better prevention and management of infectious diseases. Surveillance also helps in making evidence-based decisions. India had surveillance of certain drug-resistant organisms as part of national programs like Revised National Tuberculosis Control Program (RNTCP) and National AIDS Control Program (NACP). But a program dealing with multiple drug-resistant microbes was missing. The National Policy on AMR Containment in India prioritized the surveillance of AMR and antibiotic use across human and animal sectors. The policy advocated for the sentinel surveillance of AMR through facility-based testing. This led to the development of the National Antimicrobial Resistance Surveillance Network (NARS-NET)India launched the National Program on AMR Containment during the 12th five-year plan period (2012-2017). The program was coordinated by the National Centre for Disease Control (NCDC). The main objectives of this program are:

• Establish a laboratory-based AMR surveillance system in the country to generate quality data on antimicrobial resistance
• Carry out surveillance of antimicrobial usage in different health care settings
• Strengthen infection control practices and promote rational use of antimicrobials through Antimicrobial stewardship activities
• Generate awareness amongst health care providers and the community on antimicrobial resistance and rational use of antimicrobials.

The NARS-Net India was established to fulfill the first objective of the National Program on AMR containment. Currently, 29 state medical college laboratories from 24 Indian states are part of this network. The AMR surveillance under this network presently includes seven priority bacterial pathogens isolated from 5 clinical samples.

The data is submitted by the network labs to NCDC using the WHONET software (computerized microbiology laboratory data management and analysis program) quarterly and feedback is provided to the labs by NCDC regarding the completeness of data. The corrected data once received is analyzed at NCDC and compiled in the form of an annual report.

The annual report for the year 2020 is available here. The quality of data submitted under the National AMR surveillance network is ensured through an External Quality Assessment Scheme (EQAS) conducted by NCDC, under which all network sites submit isolates every quarter (as per program guidelines) to the National Reference Laboratory established at NCDC. NCDC has also developed various SOPs, which are updated regularly, and all the sentinel site laboratories are provided training on the use of these SOPs. During onsite visits, the lab capacity is assessed and hand holding is done for strengthening Internal Quality Control and Proficiency testing in these labs. In addition, training is also provided on AMR data management using the WHONET software. Capacity building on standardization of basic procedures in Bacteriology across the network has also been initiated using the virtual platform in collaboration with CDC, ASM and ECHO-India. The AMR surveillance network sites are also mandated to submit AMR alert strains for confirmation to NRL at NCDC. NRL at NCDC also conducts molecular characterization of the AMR strains. Annual meetings are conducted to review the working of the network labs under the program.

Antimicrobial Resistance Surveillance & Research Network (AMRSN)

In 2013, ICMR initiated Antimicrobial Resistance Surveillance and Research Network (AMRSN) to generate evidence on the extent of drug resistance and nationally representative data on AMR.

The main goals of ICMR AMRSN are to:

• Establish a network of hospitals to monitor trends in the antimicrobial susceptibility profile of clinically important bacteria and fungi limited to human health
• Include comprehensive molecular studies for identifying the clonality of drug-resistant pathogens and their transmission dynamics to enable a better understanding of AMR in the Indian context and develop suitable interventions
• Disseminate information on AMR in pathogenic organisms to stakeholders to promote interventions that reduce AMR
• Create a data management system for data collection and analysis

CMR's network focuses on six pathogenic groups: Enterobacteriaceae causing sepsis, Gram-negative non-fermenters, Enteric fever pathogens,

Diarrheagenic bacterial organisms, Gram positives (Staphylococci and Enterococci), Fungal pathogens-yeast (Candida and Criptococcus spp.) Iand mycelian fungi (Aspergillus spp. and Zygomycetes spp.) Hence, AMRSN includes six Nodal Centers (NCs) for each pathogenic group that is located in four tertiary care medical institutions. The surveillance network is managed by the coordinating centre at ICMR Headquarters in New Delhi along with the nodal centres. The six nodal centres are:

• Enterobacteriaceae causing sepsis: PGIMER, Chandigarh
• Gram negative non fermenters: CMC, Vellore
• Enteric fever pathogens, AIIMS, New Delhi
• Diarrheagenic bacterial organisms, CMC, Vellore
• Gram positives including MRSA: JIPMER, Pondicherry
• Fungal infections: PGIMER, Chandigarh

There are 16 regional centres (RC) in the network which are sixteen regional labs from tertiary care hospitals to provide data on a fixed number of isolates for each pathogenic group across the country. These are:

• Mahatma Gandhi Institute of Medical Sciences (MGIMS), Wardha, Sevagram
• Tata Medical Center (TMC), Kolkata
• Sir Ganga Ram Hospital (SGRH), New Delhi
• Apollo Hospitals, Chennai
• P.D. Hinduja National Hospital, Mumbai
• Armed Forces Medical College (AFMC), Pune
• King George’s Medical University (KGMU), Lucknow
• All India Institute of Medical Sciences (AIIMS), Bhopal
• Lokmanya Tilak Municipal Medical College and General Hospital (LTMMC & GH), Mumbai
• Assam Medical College & Hospital (AMCH), Assam
• Nizam's Institute of Medical Sciences (NIMS), Hyderabad
• Kasturba Medical College, Manipal, Karnataka (KMC)
• Institute of Postgraduate Medical Education & Research (IPGME & R), Kolkata
• Sher-e-Kashmir Institute of Medical Sciences (SKIMS), Srinagar
• All India Institute of Medical Sciences (AIIMS), Jodhpur

The NCs and RCs follow standard operating procedures (SOPs) of Bacteriology and Mycology formulated by ICMR to collect resistance data. ICMR has developed a real-time online AMR data entry system and has AMR data analysis capacity. It is a user-friendly web-based solution for the collection, storage, and analysis of surveillance data. The analysis of the data from the surveillance network provides information required for targeted antibiotic policy and

implementation of antibiotic stewardship in a tertiary care medical facility.

AMR ICMR data for the year 2019 is available from the link: Visit Webpage

To know more about the regional centres and the nodal centres: Visit Webpage

Healthcare-Associated Infections (HAIs) Surveillance in India

HAIs have tremendous implications in terms of associated mortality, morbidity, adverse patient outcomes, increased cost of treatment, and social impact. Apart from the escalating rates of HAIs, Multidrug-resistant (MDR) organisms now increasingly cause these infections. The problem is further compounded by the severe paucity of new antimicrobials, making treatment extremely difficult. An important initiating point to curtail HAIs and AMR is through capacity building to ensure that systems, policies and procedures are in place to rapidly and accurately detect and monitor AMR and HAIs. The All India Institute of Medical Sciences (AIIMS) in New Delhi is collaborating with the Centers for Disease Control and Prevention (CDC) and the Indian Council of Medical Research (ICMR) to leverage the existing capacities for microbiology and robust academic capabilities of the ICMR-AMRSN to implement a step-wise, scalable process for quantifying, strengthening, and expanding the ability of the healthcare systems in India

to generate, apply and report accurate data of Healthcare-Associated Infections and AMR. This work, being conducted under the broader umbrella of Global Health Security, includes more than 25 hospitals, representing almost all regions and states of India. This project will strengthen the national capacity for surveillance of HAIs, using the modules developed at AIIMS, based on CDC’s NHSN guidelines. This will serve the need for reliable AMR data to support successful patient care, and public health needs to measure, track and report the magnitude and types of AMR and HAI threats affecting India, in accordance with stated GHSA goals. In addition, the clinical facility component of the proposal will assess and strengthen both clinical antimicrobial use practices and infection control capacities for the containment of AMR pathogens. For further information, Click here

Challenges in surveillance in India

Creating a sustainable AMR surveillance system is a challenge. This was identified by the GARP India working group. The challenges pointed out were securing cooperation from the various stakeholders across multiple sectors, establishing mechanisms for inter-state and cross-border coordination, and financial sustainability. NARS-Net focuses on facility-based surveillance, especially from tertiary care centres. The network contains a large number of public sector hospitals and a limited number of private sector hospitals. This doesn’t provide a complete picture. There are high chances of underreporting of community-acquired resistant infections. Considering the national AMR Laboratory network in animal health and food safety sectors, India reports that laboratories perform antimicrobial susceptibility testing (AST) for their purposes are not included in the national AMR surveillance system.

No standardized national AST guidelines are currently in place. The diagnostic techniques used and the data management procedures are not clearly described in the self-assessment survey 2019-2020. Surveillance in India doesn’t cover the antibiotic consumption data. Such a surveillance system is vital to track antibiotic consumption and to predict AMR emergencies, especially today as India is the largest consumer of antibiotics in the world. As per the AMR self-assessment survey response 2019-2020, while India has designed a monitoring plan in the case of the human health sector, there is no national plan or system for monitoring sales/use of antimicrobials in animals. The situation is similar in the plant sector where there are data on antimicrobial pesticides used in plants. Surveillance of AMR in animals and food is very limited in India. Though many small-scale studies were conducted across the country confirming the high burden of AMR, India still lacks national-level data on one health. Under the national surveillance system for AMR in animals, priority bacterial species have been identified. But AMR surveillance is not routinely carried out in animal (terrestrial and/or aquatic) isolates linked to animal disease, zoonotic pathogenic bacteria, commensal isolates and specific resistance phenotypes such as ESBL producing indicator E.coli obtained from healthy animals in key food-producing species. Without adequate data on antibiotic consumption and AMR across various sectors (humans, animals, plants, food production, food safety), it would be difficult for India to amend the national strategy or to inform decision-making.

For more information, Click here