Antimicrobial Resistance: A Battle Lost or a Challenging Conquest?

Aster Medical Journal held its inaugural AMJ antimicrobial resistance roundtable in Aster Medcity Kochi. Roundtable brought together clinicians, healthcare professionals, policymakers, pharmaceutical companies, academic researchers and NGOs. The expert panel discussed the wide range of issues that affects the antimicrobial resistance response.
Antimicrobial Resistance:
A Battle Lost or a Challenging Conquest?

Dr. Anup R Warrier: Before I start, I would like to take a poll. The title of this roundtable is “AMR - A Battle lost or a Challenging Conquest”. How many of you would go with the first term? The whole exercise is a battle lost? Anyone for that?

Mr. Sampath Kumar: Not yet

Dr. Anup R Warrier: Zero? Can I conclude that all of you are thinking of it as a challenging conquest? It is great to know we are optimistic. Since we represent a multitude of stakeholders, I am trying to take this from bottoms up. I want to start the discussion with Dr. Rajeev because he is a practising physician, besides holding the added responsibility of the Presidentship of the Indian Medical Association (IMA), at Kochi, which is a large association of practising doctors. He also has administrative responsibility in his hospital. So, he is the apt person to start off this discussion.

My first question to Dr Rajeev is, what are your observations regarding the awareness about the Antimicrobial Resistance? Does the “Antimicrobial Stewardship Program” come across as a solution among the doctors, especially among your IMA & Hospital colleagues, and various other people you come to face in your fraternity?

Dr Rajeev Jayadevan: Well, we are located in the town of Kochi, the academic capital of the State of Kerala; in a sense, we have a medical education program happening practically every day. Practising doctors meet in rooms like this and discuss academic topics. From that standpoint, the doctors in this part of the State are no strangers to the term Antibiotics Stewardship. Kochi is a town buzzing with academic activities, but that doesn’t represent the rest of India. So, I want you to keep in mind that distinction very clearly. Thus, the standard of practice around this area could potentially be of a higher standard than in the rural segments of the country where there is no access to CMEs.

I represent the Indian Medical Association as the President of the local chapter. We have several initiatives to reach out to doctors who are in practice. When I say the CME program, there is a set group of doctors who attend these programs. And there is a vast majority who never comes for these programs. That is our target. That is the group of people we need to be addressing. I always say that there is something called the seminar paradox. The seminar paradox is - that the people who attend the seminar are not the ones who need the seminar. The ones who need the seminar are always outside the seminar. So we must make ways for the ideas to reach the grass-root level.

Dr. Anup R Warrier: What do you believe are the challenges in managing this problem? What are the challenges in handling or managing AMR and getting proper compliance with the AMS initiatives and strategies in your hospital?

Dr Rajeev Jayadevan: Rational use of antibiotics is twofold. One side, they are often wrongly prescribed. The flip side is when they are needed; they are not prescribed. So, we need to address both sides. From a practising doctor’s standpoint, I would equate it to the garbage case in the country. I am sure you have travelled widely enough to see garbage piling up on the roadside. That is because; it is multifactorial. If you take a look at an area where garbage is piling up; you see one person going and depositing his junk, then you see another person seeing this person depositing junk, and says “Okay. Let me go and put mine as well”. Now you have two pieces of garbage. A third guy says, “Well, that is the official place to dump garbage!”, so, this is a self-fuelling process. Bad prescribing patterns work like this. Seeing your colleague prescribing or talking about antibiotic use for a mild condition or you see their notes. We see our patients, and we share similar notes, we learn passively seeing that an antibiotic is prescribed. We may not be learning actively. We learn the practice from other people. So when we see wrong practices around us, we tend to copy them. And we don’t have corrective measures often enough. We don’t have audits often enough to stop this copying process. So, this results in a large pile of garbage because when everybody thinks the other person is doing the right thing, then collectively, we are all doing the wrong things. That is the way I would equate the antibiotic prescribing practice in our country.

Dr. Anup R Warrier: Do you believe that good audits on the antibiotics prescription practices where you provide feedback to the prescribers would be some part of the solution?

Dr Rajeev Jayadevan: Yes, but again, audits will affect only a small segment of the prescribing physicians. Because audits are typically in academic settings, but the vast majority of practice does not happen in an academic setting. If you ask me, what is the best way to reach out to them? When I say ‘them’, I do not mean somebody who knows less than me. It could be me sitting alone in a clinic somewhere. The best way, in my opinion, is to create a list of the most commonly prescribed situations, what are the situations where you do not need antibiotics!. Educate them from what I would say, the wrong end of the equation. Rather than telling them what is right, tell them what is wrong. Often Antibiotics Stewardship meetings talk about the transfer of resistance, plasmids, horizontal transmission etc. The practising physician doesn’t care about mechanisms of resistance, he cares for a sore throat in a patient coming his way, a patient having a fever or a woman who is having dysuria. We need to create easy solutions, workable solutions for these people so that they will know that for uncomplicated sinusitis I don’t need antibiotics.

Each of them has a reason for over-prescribing; each of us has a patient’s case that did not go right. I have an uncle who died because his chest infection was treated with a low-grade antibiotic. He died at the age of 59. He should have been alive and well in his 80s at this moment. And that happened in Trivandrum in one of the largest hospitals. He had total lung destruction because of progressive pneumonia. That is another example of antibiotic use which is underprescribed. All doctors have experiences like this, so when a patient comes in front of them, they don’t want to take a chance. They are not bad people; they just want their patient to get better.

Dr. Anup R Warrier: Dr Aravind has visibility at the Kerala government level. Kerala has taken the lead in the AMR activities across the nation because Kerala was the first state to launch this. Please explain the various steps taken by the Government of Kerala to fight AMR?

Dr Aravind R: From 2013 onwards, unofficially, the Government of Kerala has been tracking resistance. It was mainly through microbiology departments in the major medical colleges in the State as well as from the NABH accredited hospitals. In 2017 the National Antimicrobial Resistance Program (NARP) came into force in India, the states were invited to a workshop, and were given the task of developing their Action Plan in a five year time. Kerala took the cue and became the first state in India to release its own Action Plan. That is “KARSAP” – Kerala Antimicrobial Resistance Strategic Action Plan, which was released by the honourable Chief Minister, on October 25, 2018.

Why the Chief Minister is the crux of the question. Because AMR is managed under multiple ministries. When the Delhi declaration came in 2017, 11 ministries came together with the AMR declaration, because it is not only the health department alone which is concerned. We need to have different ministries as; Animal Husbandry Department, Environment, Aquaculture and Fisheries. We want the Ministry of Finance to support us. At the National level, there are around 11 ministries. So ideally it should be the Prime Minister who is heading the national program. But unfortunately, it is the Health Minister who usually heads the program. So the Environment Minister may not listen to the Health Minister. So in Kerala, the initial aim of the state was to have the Chief Minister to head the program, and that happened. So all the other departments are working under the Chief Minister of Kerala even though it is coordinated by the Department of Health and Family Welfare. What we are following is the ‘One Health’ approach.

We have the six strategic priorities under the KARSAP. First, is knowledge and awareness building. Second, is knowledge and evidence, that is, through surveillance. Third, is infection prevention and control. Fourth, is antibiotic stewardship. Fifth, is research; for which the Rajiv Gandhi Centre, which is a Central Government Institute, is our partner. And the sixth is the most important one:public-private collaboration. All these six strategic priorities cut across all the aspects of the ‘One Health’ approach. When we speak of knowledge and awareness, it is not about creating awareness among doctors alone; we tackle the farmers, horticulturalists and aquaculture persons.

Additionally, India has not banned over-the counter-selling of antibiotics. Even though we do have Schedule H1 as well as Redline campaign, the ground reality is that all the antibiotics are still available over the counter. Even though the situation is far better in Kerala compared to other states, it is still a reality. So, we cannot just blame the doctors. We need to engage the public as well because antibiotics are readily available at the pharmacies. In 2019, the objective of the state was to educate everyone; All the consumers, all the pharmacists, as well as the public. And the Kerala Health Minister declared that by the time of ‘Antibiotics Awareness Week’ next year (November 18, 2020), Kerala would become an antibiotic literate or aware state where everyone in Kerala will be aware of 10 basic facets.

Regarding the second aspect, the surveillance looks at the ground level resistance data. Where we started, in 2018, we had around ten labs reporting to the nodal centre, that is the Department of Microbiology, Trivandrum Medical College, and we had an NCDC site that we reported to. And from there our data is being reported to GLASS, that is a global surveillance system. Then we came with some interesting observations because the ten labs which were reported happened to be the medical college hospitals as well as a District Hospital Ernakulam. The resistance rates, even between the medical colleges, were entirely different. Trivandrum having more critical care support had more resistance rates. Small medical colleges like Alleppey, Kottayam the resistance rates were pretty low. So we decided not to have a state-level antibiotic policy or guidelines like the national guidelines, it may drive up the resistance if you are following the guidelines based on data only from the tertiary care centres. It was like a microbiologist paradox. If you follow the guidelines, we may drive up the resistance rates. So, the Kerala government decided not to have an antibiotic policy or guideline for the state; instead, we said that all hospitals should have their own AMR guidelines.

Then, we started with the second aspect of this KARSAP. To come up with KARSNET – ‘Kerala Antimicrobial Resistance Surveillance Network’ where we incorporated 17 other hospitals as well as the labs so that we can get data from the ground level representing the primary health centre, as well as the secondary health centre. And so now we do have the data representing all levels of care in the State of Kerala. That is KARSNET.

Third, is the Infection Prevention and Control. Our focus is really on Infection Prevention and Control. People who were on the frontline fighting Nipah, in Calicut, were people who got training under KARSAP. That actually can be counted as one of the successes of KARSAP, because Infection, Prevention and Control were given such support by the state government.

Fourth, is about Antibiotic Stewardship, not only on the human side but also in animal husbandry and aquaculture. We are addressing the low-hanging fruit. All the hospitals cannot have a restriction or a prospective audit and feedback; thus, we do insist on certain things only to start with, except in the tertiary health centre.

The research aspect is going on in all fields. Animal Husbandry, Agriculture, everywhere it is going on. All the data is being collected by the Rajiv Gandhi Centre.

Sixth is the public-private collaboration where we are working closely with an NGO – Centre for Science and Environment - to help us with environmental surveillance aspect, chart out the good farm management practices, as well as ensure the biosecurity guidelines and waste management practices in farms.

One advantage of Kerala is that we don’t have that much of big pharmaceutical industry, so the affluence from the pharmaceutical industry is not a major problem for Kerala, but the affluence from the hospitals are. Those aspects are being taken care of with the help of CSE.

These are the initiatives taken under KARSAP.

Dr. Anup R Warrier: In infection control, what kind of capacity building has been done? I know that posts are being used as infection control officers. Can you give us more details?

Dr Aravind R: Even before the KARSAP materialised in 2017, an examination was conducted in almost all the government hospitals to select five to six nurses and were given a 7-day training by the Director of Medical Education, and they were designated as infection control officers in their respective hospitals. A major problem with the hospital is that the Trivandrum Medical College has around 3500 beds. So ideally, we should have around 35 infection control nurses. This is practically impossible, and we have only two infection control nurses. Another system is that we have link nurses and mentor nurses. They double up as infection control nurses. And this link nurses system has been spread across the state, and all the hospitals now have link nurses. Infection control nurses their function is only infection control, auditing and all those things. Link nurses do their job and double up as infection control nurses.

In a resource limited space, this is the only thing which works. As far as infection prevention and control, Nipah was a blessing in disguise. Everyone became aware of the importance of infection prevention and control. Our hospitals are very crowded, the situation has not changed much, but the situation in ICU has improved a lot. The situations in the ward, OP, and casualty are still out of control, but what we have observed is that the resistance is more of a problem in the ICU. So we are focusing our work on the ICUs.

Dr Rajeev Jayadevan: What are link nurses? What does that mean? Is it as in L-I-N-K?

Dr Aravind R: Yes. L-I-N-K. We are doing surveillance on three fronts under the KARSAP. One is the healthcare associated infection surveillance where we look at the VAP rates, CLABSI rates, CAUTI rates, SSI rates etc. Link nurses are the ones who collect the data from the ground level – that is the ICU levels, and they have a computerized system. Otherwise, they would write it down and convey it to the infection control officer who in turn will convey it to the Infection Control Committee.

Dr. Anup R Warrier: The sixth point mentioned was a public-private partnership. What are the opportunities existing as of now, where is the private partner with the government in this program, and what kind of partnerships have already occurred? What are the things you are looking for, for partnering with private institutes?

Dr Aravind R: For KARSAP there is no split between private and public because AMR is not my problem or your problem, it is our problem. KARSAP is headed by Amrita hospital, the private sector in collaboration with IMA is looking after creating awareness and all aspects of AMR in the private sector, and we do have six other partners. We have signed an MOU with the Government of Kerala BD, Beckman Coulter, BioMerieux, DSM Sinochem CSE; and recently, a group of ID physicians and microbiologists in Kerala came up with an app to help the students. So the contents are verified by the KARSAP committee and also are a part of it. Anyone in the private sector who is contributing to AMR is welcomed to be a part of this program because our aim is to make Kerala an antibiotic literate state by next year.

Dr. Anup R Warrier: Thank you Aravind. Moving on to Dr. Geetanjali from CDDEP. CDDEP has a tremendous amount of surveillance data from the national level, as well as through its visibility at the global level. When looking at the website of CDDEP, we see that it is very rich in data. You have a lot of prevalence studies, incidence studies, and coming on MDR and AMR data.

Despite this much data available in the sphere, just as Dr Aravind just said, when it comes to local implementation, the first thing we say is that we don›t have local data. So, let us wait and try to generate local data. Do you think it is essential for every unit at the local level to generate enough data? And do you think data will be vastly different from what you have accumulated from across the nation?

Dr Geetanjali Kapoor: CDDEP is a public health research organisation incorporated in 2010, headed by Prof. Ramanan Laxminarayan. CDDEP has various flagship programmes. One of them is the resistance map; that is an interactive tool that provides the data across different countries for AMR and AMU. AMR data reaches us through various networks across countries. So we cover over 70 countries, and the data reaches us. For example, in India, we have data coming from the Fortis SRL Labs, Vietnam, it comes from the Vietnam network. When we receive the AMR data from the labs, and we do a second-level run on that data before publishing it as a map on the CDDEP website. So everybody can view that. It’s not representative of the entire country for sure. It does not mean that we need to wait for data to come from everywhere. We don’t have as much time as we know because we say a “battle lost”. I would say that it’s lost if you do not take action now, with whatever data we have, yes, we do press for more data, we are encouraging our partner hospitals to share the data with us.

Dr. Anup R Warrier: Do you have any plans to have a map for infection prevention control or hospital-acquired infections?

Dr Geetanjali Kapoor: I think you have raised a perfect point. We shouldn’t restrict to either AMR or AMU. We should map as much data on hospital-acquired infection, devices associated, even community-acquired infections. However, the data collection has to be done as per stringent quality standards, because if you have data on your records or on your registers, that is not through a proper quality system. That collected data will not be useful in the end.

Dr. Anup R Warrier: Willemien, we will come to you now. From an international perspective, in the Netherlands, as we know, the per capita consumption of antibiotics is quite low. What do you think is the contribution of infection prevention to achieving the lowest per capita consumption in the whole world?

Dr Willemien Maathuis: Standard precautions in the hospital.

Dr. Anup R Warrier: Do you think you have the best infection control compared to the US & UK?

Dr Willemien Matheuis: Oh No, I don’t think we are the best. We have the same problem that you have here in India. This morning when I was talking to the infection prevention control team in Aster Medcity, I heard that infection prevention and standard precaution is so simple. Everyone can do it, you have to do it. And that’s the problem. You see, nurses mostly do it well. But other people in the hospital don’t do so well. And we all know it. We have the measures, we have the guidelines, but the change of behaviour. That›s the most important thing.

Dr. Anup R Warrier: Did you structure the program there so that it works, and how?

Dr Willemien Matheuis: Yes, when your basic hygiene is in order, then the hospital-acquired infection gets lower. The compliance is higher, and the infection gets lower. So, infection prevention control is simple, but everyone has to do it. And that’s the problem. And the change in behaviour is very problematic.

Dr. Anup R Warrier: When we visited the Netherlands, there was this session on change management & changing behaviour. That’s very new because in our regular curriculum it’s not there.

Dr Willemien Matheuis: It begins with educating doctors and the nurses, in the first year we have infection prevention education. The knowledge, the risk you take for the patient, and for yourself, it’s a part of our curriculum.

Dr. Anup R Warrier: The doctors mostly drive the antibiotic stewardship as of now, what do you see the role of nurses and pharmacists? In the Netherlands do you have the involvement of the nurses and pharmacists as some decision makers anywhere in this whole structure of AMS?

Dr Willemien Matheuis: Yes, nurses play a significant role. They even change or regulate the antibiotics as per the patient improvement. Nurses decide to change antibiotics from IV to oral. The active involvement of nurses in monitoring and promoting the best governance plays a crucial role.

Dr Anup R Warrier: Peter, Netherlands has the lowest per capita consumption of antibiotics for humans, but has the highest per capita consumption of antibiotics among animals. Nowadays, we hear this from clinicians when we discuss antibiotics, 80% is used in animals, so why are you coming and talking to us! Does this mean that heavy use of antibiotics in animal husbandry and fisheries doesn’t directly contribute to AMR rates in the community? Or is it that food hygiene is so good that it does not translate into human resistance?

Dr Peter: We indeed have very high antibiotic use in livestock. So how come it doesn’t reflect on the human situation in hospitals? I think AMR is a very complicated problem, and you only address it looking at ‘one health’. ‘One health’ means you have to look at the communities where you live, and you have to look at hospitals, and you have to look at livestock. You also have sanitation, hygiene and quality control, like in hospitals we have infection control, in livestock you have the control of the food whether it is safe or not. Of course, you have waterways and waste problems, so it’s a very complicated thing. Now if you think, for instance, Holland and Kerala are almost equally large. If you consider this as a country, we are almost similar. We have abundant water areas, we live in a delta, and you have a lot of water, and you live in a delta. Why it’s different in Holland, and why high antibiotic consumption in livestock does not reflect on hospitals!

We have about 100 hospitals in Holland, and the number of beds is decreasing very rapidly, so patients come in the morning and leave in the afternoon. We almost have no long-stays. We have renovated all our hospitals in the last 15 – 20 years, they are all quite modern, this may be an essential factor. I don’t know. If you look, for instance, the emergence of MRSA, in the 90s, Netherlands and Great Britain had the same problem of low resistance levels, and what we did in Holland was aiming at fighting MRSA right from the beginning. So anyone with MRSA was placed in isolation and treated, and we got rid of MRSA.

In England, they did not do this. So, ten years later, there was more MRSA per capita in England compared to the Netherlands. They were very alarmed about this. It took them ten years to take general precautions to come back to the level that we have in Holland. So this explains the power of just general infection control. Maybe targeted to specific situations.

After that, we started to use a lot of antibiotics in livestock. I live in the south of Holland, and that’s where we have the most livestock in Holland. What we saw was a tremendous increase in livestock-associated MRSA. This came directly from pigs; they were given antibiotics as a growth factor. They developed resistance, and because a lot of people were working in farms in our area, they got infected, or rather contaminated, with LA MRSA from pigs directly.

They came to the hospital, and we didn’t find many infections, what we saw a steep rise in the prevalence of LA MRSA. This caused a lot of public resistance, and they executed a new law, that bans giving antibiotics as a growth factor. When antibiotics are given to livestock as a growth factor, the animals grow better and have less disease, so it’s very profitable economically. So they said we want to stop this, and what we see now is that five-six years later the prevalence of LA MRSA is going down.

If in Holland, we see a patient with NDM, we are almost sure that it’s someone coming from India. So how come? If we have someone with NDM we get alerted, we had a large outbreak in our hospital with NDM, probably you have read about it I am not sure, because we never had NDM before, we started an outbreak control. What did we do? We just said we have to do general infection control practice. Nothing extra, just what’s usual, but we have to adhere to it, as we had 30 patients with NDM all of a sudden. Only doing that stopped the epidemic.

But interestingly we found that the NDM gene was not only in E. coli but also in Klebsiella and Enterobacter. So if we had not genotyped at the laboratory, we would have fought three different epidemics. What happened is that the resistant gene plasmid was able to go from one to the other species. This can be very confusing. In Holland, there are only a few epidemics, and we know we can fight them very effectively by simple infection control measures.

Dr. Anup R Warrier: From being a medical microbiologist, how important do you think it is for a country like us to invest in molecular diagnosis. As you said, you had an outbreak, and you used molecular diagnosis. Nowadays it is all about molecular epidemiology, so being in an endemic setting, and even for diagnostic stewardship part, for faster diagnosis and more accurate diagnosis etc., do you think that introduction of molecular technology in India, in infectious diseases, will help us or complicate things more?

Dr Peter: It will help on a national level to understand what’s going on. If you know where the clones are going, and what the drivers are, if you see a particular gene, very prevalent intakes, you know you have to go there. If you see it’s in the community, you have to go there. On a national level, it’s vital. I would look at the hospital level, and I think a quick and accurate diagnosis of infections is crucial. That’s life-saving and cost-saving. We had a large epidemic in Holland of Q fever, all these patients were treated with beta-lactams because nobody knew it was Q fever. Hundreds of patients got the wrong antibiotic which resulted in an average length of stay which was double than usual. If we had a proper diagnosis, we could have saved lives, and we could have saved a lot of money. I believe molecular tests will help us in quick and accurate diagnosis for sure.

Dr. Anup R Warrier: We have two industry partners with us from BioMerieux and Pfizer. Can you share with us some of the initiatives from BioMerieux? What are your contributions or initiatives in controlling AMR?

Mr. Sampath Kumar: Thank you so much for inviting us to this Roundtable. I represent BioMerieux. Navjeet Singh is the head of our medical affairs and Asia Pacific lead for AMR. And I am here on his behalf. First of all, the philosophy of BioMerieux is that diagnosis is power. That drives us. As we know, the diagnosis has played an important role in isolating and curbing down the infection rates. What we hear is that 70% of medical decisions are based on laboratory results. But how much is being invested in the labs is like less than 10%. As a structured program for our customers; not only for our customers as such, for anyone in the industry to join this global point prevalence survey - with the help of the University of Antwerp in Association with Biomerieux . Only as monetary support. And it’s a purely voluntary basis - customers can go into this program - it’s a one day point prevalence survey. It started in 2015, and around 17 hospitals across India participated in this and shared the data with us - and they were given an individualized report on their way of antimicrobial prescriptions and their resistance rates.

If there was any need for improvement, it was shared with them. It turned out to be an excellent tool for them to analyse themselves – the way they are doing their antimicrobial stewardship. This year we have targeted 75 hospitals, 50 we were able to achieve. Fifty are there - as a part of this global point prevalence survey. And it is entirely free of cost. That is one structured way of involving in the antimicrobial stewardship. We also support world antibiotic awareness week every year.

Dr. Anup R Warrier: What does BioMerieux understand about the QC & standardisation of microbiological reporting? Do you have any program focusing on the smaller lab which caters to a huge group of private practitioners on standardization of culture reports and in terms of reporting and background.?

Mr. Sampath Kumar: We do a lot of educational activities where we target lab technicians, nurses, and also the clinicians on various aspects. For example, for clinicians, we harp upon the number of blood culture bottles. For nurses, the volume of blood and the aseptic collection aspect. For the technicians, how fast he should process samples to reduce the turnaround time for the patient, these aspects we harp upon. When it comes to antimicrobial resistance, we speak to the doctors about the importance of having the way of doing the right antibiotic prescriptions. For example, with the help of the culture. So what we have been harping upon is to inculcate the concept of prescribing culture because in many places, it is in the OP setting; straight away, the antibiotics are prescribed without doing any diagnostic test. This leads to a lot of antimicrobial resistance.

Dr. Anup R Warrier: What are Pfizer’s initiatives to Address the AMR and AMS issue ?

Dr Sonali Dighe: Globally, Pfizer has been doing a lot of things in this space of AMR. Right from an earlier time, as well, but they have become more serious about this after the science declaration, the diverse declaration where about close to 100 pharmaceutical companies have come together and sort of pledged their support to curbing AMR in the world. Even there if you see the roadmap for reducing AMR, the aspects, the pillars are very similar to what you had mentioned. We start with AMS, the Antimicrobial Stewardship. There is surveillance. There is also this bit about prevention, and I will talk a little bit more about prevention.

As far as AMS is concerned, there are several initiatives at different levels that are going on. For example, at the tertiary care level, the initiatives are more around education; having training modules that are being used for educating the clinicians, even the pharmacists based on the need. There is also this capability building initiatives like infectious disease fellowship. There are these international partnerships like the Academy of Infection Management where there is a certification program that the doctors can take up.

If you look at the smaller nursing home, the secondary care, at the smaller nursing home, the main problem is that they do not have an antibiotic policy specifically. So Pfizer has been working with these nursing homes to work on their own antibiotic policy. Everyone will have slightly different data based on their susceptibilities in their hospitals plus their prescription data. Based on this, they plan their antibiotic policy, and we hope that they can see before, after, and actually see the difference and hence will continue to use antibiotic policy. Because we believe that we can do one intervention, second intervention, but after that, the nursing homes will have to take it ahead by themselves.

In India, a nursing home is a smaller hospital with about 15-20 beds. And then at the public level, there is our association with ICMR where we did have a public awareness campaign about the misuse of antibiotics. Because there is a lot of OTC antibiotics usage in India, which all of us are aware of. So there was this campaign about not using it until prescribed by the doctor, and once prescribed also, taking the right dose for the right duration etc.

So that is something we are currently doing from the AMS perspective. Coming to surveillance again, there is a global program; we are calling it ATLAS, where there are more than 70 sites in the world, a few sites in India as well - surveillance from susceptibility data for different molecules has been looked upon over the years.

The third bit and again I would think that is an important bit that often gets missed out -prevention. Prevention in terms of vaccination. That’s one of the important aspects of AMR according to us.

Again, vaccination at the paediatric level. We are aware of it because the paediatrician is the one who asks to go for vaccination. There is a very clear national immunization program there. Going ahead, what we want to do is also to talk about adult vaccination, which is at a very rudimentary level in India. Then you avoid infection in the first place, and hence AMR.

The last bits I would say R&D, while there are a couple of molecules we would be launching. All of us know that the pipeline is not very great, but at the global level Pfizer is working with the regulator in terms of how can we get molecules, how can we work on the real-world data and hence get new molecules. And there are those aspects that Pfizer is working at the global level. So this is broadly about what we have been doing.

Dr. Anup R Warrier: The second question is about the poor quality of drugs. Organisations, including the World Health Organisation, have mentioned the poor quality of antibiotics as being one of the drivers which drive antibiotic resistance. So what are the regulatory and compliance structures which are in place in India to address this issue as of today and how far has this been successful?

Dr Sonali Dighe: And that actually reminds me of the importance of good manufacturing practices. I think India, from a few years from a regulator’s perspective, gained a lot of awareness about the importance of manufacturing practices. So what we know is that - not just OTC prescription and the H1 Schedule, the drugs under the H1 Schedule that the Indian regulatory bodies have got into. But also there is a push to increase inspections. There are drug inspectors who actually visit the manufacturing sites, and they can take samples from any manufacturing site. They can take samples from the pharmacies and get them tested at central laboratories. The government has increased the number of drug inspectors as well as the central laboratories. If they are sub-standard, then they get back to them. The medicine may have to be withdrawn from the market. And in fact, they do publish the data on the website as well. So there is this awareness among everyone about the importance of substandarization of medication.

Dr. Anup R Warrier: What about the approval level? Just last week I saw promotions for meropenem, sulbactam and meropenem & EDTA Combinations by good companies. If you look at WHO list, there is a whole lot of medicines which are in the non-approved list in the World Health Organisation schedule, and there are many companies which are launching this non-approved combination by World Health Organisation to the market as recently as you know this month and last month. Are there any regulatory frameworks at the approval? If somebody comes out with an A-plus B combination or antibiotics B or C, is there a system where the government or the Drugs Controller looks at?

Dr Sonali Dighe: Actually there are. By the Drug Controller General of India through the subject expert committee, there is a very clear process of approving the drug. So when I have to apply for marketing authorisation, there is not just the clinical trial data, but data of Indian patients has to be submitted and also data of manufacturing practices has to be submitted. And you know API level data has to be provided. They go through this data. As some of you might be aware, now our regulators insist on Indian patient data.

Dr. Anup R Warrier: How did those combinations come into the market?

Dr Sonali Dighe: I don’t know. Probably they have shown Indian patient data. I would not know to that extent. If you look at the framework, there is definitely a framework. A very stringent framework to see through that there are the right molecules, and the right products come into the market.

Dr Geetanjali Kapoor: I would like to comment. We also need to address the fact that some of these drugs are coming not from within India but from the borders, especially spurious drugs. There are markets which are outside India, and the borders are so porous, I think till we have an international agreement and international strict regulations, all that you do, it would be a failure because the drugs are coming from China, from Vietnam, from Nepal, from other countries. I think the porous borders and regulations need to be tightened even at those levels. Apart from this, 68% of the fixed-dose combinations are not registered with the Central Drugs Standard Control Organisation, the CDSCO. So that’s a huge number. 68% are not registered, but they are available in the market. This was in the year 2017, so I don’t know the latest figures. But a huge number of FDCs are still unfortunately in the market.

Dr Rajeev Jayadevan: Dr Sonali talked about substandard medication. I am sorry to say, but in India, with all the heterogeneity in the health sector, we also have some substandard prescribers. A large number of prescribers from a healthcare provider is not from an MBBS doctor. And that is a fact. In some of the larger towns outside of Kerala, I am told that the majority of general practitioners are not MBBS graduates. MBBS is a basic medical degree. And these individuals control the market. I don’t know what kind of standards they are practising with. So when we talk about substandard medicine, we must also talk about substandard prescribers.

Dr Geetanjali Kapoor: Even the online pharmacies are openly selling drugs though they are not supposed to be sold over the counters.

Anup R Warrier: Now I am going to invite Dr Harish Pillai. When you sit around with other CEOs of other hospitals in the country, does this thing come at all? Do CEOs talk about Antimicrobial Resistance?

Dr Harish Pillai: You are trying to strip me naked. Honestly.

Anup R Warrier: There is a specific reason why I asked you because the UN is saying that the GDP will drop by 3.8% by 2050 because of AMR.

Dr Harish Pillai: Like many of us, for the right reasons, we start questioning Donald Trump and his theory on climate change, where many Americans, especially those in the Trump faction think that climate change is a hoax, and is not based on science. Unfortunately, the reality is that the CEOs around the world, especially in the private sector, their priorities are entirely different. And these kinds of discussions in a hospital set up, even in large enterprises are learnt from the clinical leadership level. I would not say it is the management level.

Anup R Warrier: What would be the roadmap ahead for Aster DM looking at the focus of AMR and antibiotic use. Where do you see in another five years the Aster DM doing in the field of AMR or infectious prevention or AMS?

Dr Harish Pillai: For Aster, because we are a multinational Indian healthcare entity. We are presently there in nine countries. Our presence in India is rather small compared to our presence in the GCC. We are the largest primary health providers in the GCC region with extensive investment in primary and secondary care because demographics in countries such as UAE, especially in the city of Dubai, is such that it is mostly a clinic and ambulatory practice.

But in India, the spectrum is different. All our hospitals are focussed on tertiary and quarterly care. The institution where you are sitting right now, the Aster Medcity, is a classic example of what Aster would like to do in India. We have a big portfolio of hospitals across five states, and the way we have set up Aster Medcity is to create a certain benchmark of best practices across the spectrum.

Just to give you a snippet about that, this hospital is the result of an epidemiological study of the state of Kerala where we realised the rapid ageing of the population and extensive prevalence of type II diabetes. We established the centres of excellence which are just focussing on eight to nine spectrums. So from NCD point of view, what is really necessary for our community in Kochi or in the larger state of Kerala is cardiac, orthopaedics, neurosciences, gastroenterology, oncology, women health, metabolic diseases, critical care, multi-organ transplantation, so that is the focus of this tertiary care hospital.

And the resource planning, whether in terms of capital allocation of resources or the manning plan, all support the larger epidemiological data that flowed through when we set up this hospital. I would say this was the easy part. The tougher part was to set the culture. And many of you mentioned behaviour as a critical part of sustainable programs. When we started this hospital, in fact, I was the first CEO of the hospital, it was left to us to ensure that we hire right. And we built the concept of a collaborative team. The idea was to deploy clinicians who knew their limits. We didn’t want to have cowboys in the system. We ensured that algorithms and evidence are set from Day 1.

Like Dr Warrier, I had the privilege of hiring him. He was from Day 1 the single point of contact for infection control and infectious diseases. And it was very obvious, even though you have senior colleagues in Internal Medicine, or the subspecialties of medicine, when they have a moment of doubt, the question has to be raised to Dr. Warrier for an expert second opinion. So that culture was built in from Day 1.

The second aspect, in addition to behaviour, was the investments we made in IT systems. We had a very robust electronic recording system from Day 1. We said there would be no paper medical records in this hospital. Ambulatory and inpatient data will be entirely electronic medical records. And you have a decision support system embedded into that. And the conversation which all of you had on nursing. We have a very empowered team of nurses. We used to encourage the nurses to pull the chain. If they had a doubt, whether in terms of prescription or anything else. Nurses are highly empowered.

The third important aspect I think is the clinical pharmacy, the whole cadre of clinical pharmacists. Aster Medcity has a total of 13 clinical pharmacists. I know that this is probably one of the few hospitals in the state of Kerala and even in South India, wherein one institution has 13 clinical pharmacists.

We have a large number of education programs. We have about a hundred postgraduate students being trained in this hospital, both from the national board of exams and they have a very interesting program accredited by the three royal colleges of physicians for IMT - Internal Medicine Training. All these postgraduates also get to have that element of the important role of AMR, the other aspects, the cultural aspects are embedded into them.

We are also generating a new generation of clinicians who would hopefully have altered behaviour compared to the set rate.The beauty of running a hospital in Kochi and I would say, I would dare say in Kerala also, is the quality of other hospitals. Like we have a large representation of public sector as well the private sector. It is a real pleasure where people do not hesitate to reach out and share knowledge just because you are a competitor hospital. Between societies, we have a strong bond. You have a lot of these societies, for example, the Gut Club in Kochi. Many of these societies have a lot of fraternal relationships across the state of Kerala. There is a symbiotic aspect to spreading knowledge, and that elevates the practice structure in the State overall.

Answering Dr Warrier’s question is that, the good things which we have done in Aster medcity, we are trying to spread across Aster India because I have a benchmark in Kochi. So I ask my colleagues either from infection control or from quality, from the rest of India to come to Kochi and learn from their colleagues; because they have already been doing that for the past six years. Ultimately the way forward is, this hospital is already doing a joint commission accreditation and all the joint accreditations; I am also trying to get all the other hospitals in India to go through the same path, the same path as Kochi hospital.

We are also now investing in the database in software where the clinical outcomes, for about 15 specialities, would be published and also shared with Institutions overseas. We can benchmark our clinical outcomes—both for specialities and for physicians.

Dr Anup R Warrier: Dr Satish, What are the technological innovations that we can look forward to? At two levels.One, the technological innovations which are out there in the world, but may or may not be financially feasible for us. Second, what are the innovations which you think you can bring down to our organisation and we can look forward to using in the near future?

Dr Satish Rath: We have two technologies understanding biology, infection and genomics well. It’s a semiconductor technology that we can call lab-on-a-chip. You put any fluid, and you can analyse it at a very cheap cost. We were always able to analyse this. But the computation power was very high. Maybe a computer of this-sized room. What we used to do in 2003 or 2002 has come down to a tiny fraction of things.

And the cost of computing has also come down drastically. So we have chips for everything, and we have the power to compute it at the point of care which is making a lot of start-ups coming into local diagnostics.

On the other side, we have a lot of data exploding - the power of AI, which has improved over the last four to five years. You put any data, and you can churn out the real insights. Why do people prescribe even when they are not sure about something? They do not want to miss out. An antibiotic need might be there, and there might be a bacterial infection. I don’t have a diagnostic to tell me whether this is a bacterial infection or a non-bacterial infection. I believe these kinds of technology which can quickly diagnose it’s bacterial or non-bacterial that would be a real game-changer. The good thing is that its happening. The technology is coming very fast from countries like the US, Israel, Australia, Singapore and some parts of Europe.

The second piece is, as we understand in Biology as the doughnut model. As a scientist, you see the doughnut with the middle portion, which is empty, that is microbiomes. The microbiomes are controlling the NCD’S, the infections, the immunity and the inflammation. There is gut-brain access. So how we are thinking, how we are handling the external pathogens, is contributing a significant part into it.

If I have taken a certain kind of food, I am particularly vulnerable of being exposed to certain types of microbes, and my susceptibility to infection and infection resistance power. It would be beneficial if the government takes it up to have a microbiome database. So that we understand this is the microbial pattern of people who are resident in Kerala or say migrant from Kerala. And you can then correctly prescribe what kind of antibiotics they should be taken based on the microbial pattern.

There is a start-up in Israel called k2, which has started this area, and they already have two publications in nature. Before you are prescribed antibiotics or NCD drugs, your microbial analysis is going to be done, which is a very cheap thing. Because the sample is the stool, and you are going to be prescribed personalised antibiotics. This reminded me of one of our researches when I was in xerox lab. We invented something based on normal cellulose, paper, what is used for printing, and we can print it with wax, and this can act as a lab-on-a-chip. So, the cost of a lab-on-a-chip is just the cost of your paper. We had worked with WHO to make it widely available, we had samples for E.coli, and salmonella, shigella and work is still going. Why I am citing this is because technologies are available, which can make it available at the doorstep of each and individual patient before they are prescribed anything.

When we say aIl kind of data, real-world evidence data becomes very very important. You have data which is getting generated, if you have real-world data, what we call real-world data is citizen data plus enterprise data. Consider citizen data as whatever my online data, my behaviour is there, from my phone, there is a humongous amount of data which is out there. There are good companies which can mine it, through Artificial Intelligence, and then you know there is the enterprise data, which is the AMR data or PHR data, let’s say surveillance data. When you combine these two, citizen data is up to 70%, and enterprise data is up to 20%, you have a remarkable amount of specificity in the insights. This is seen as the next big thing.

When you use AI in unsupervised learning, an area where we throw any data, AI identifies which are the closest patterns, what we call as clustering. Now we have started to understand what are the older antibiotics which have been put out of use, can be used to treat particular infections. And this is a significant discovery where we are having the falling of the pipeline of the antibiotics. If you ask any of the pharmaceutical companies they will say, they are apprehensive about not having the new molecules not coming up. Still, here we have an opportunity where we can identify which antibiotic might work for which demographic, which localisations, and entirely for a newer indication, which was not identified. So, if we use lab-on-a-chip we can have a diagnosis part, and this is very much possible, we should not think that this is very much expensive. And the entrepreneurship should be driven by both government and private partnership. Birac, DBT, other funding agencies are supporting things like that, and this should be done. I would see this is the best part of a public, private partnership.

Dr John: Dr Harish was saying that driving AMR is a clinical activity. I will fully agree with him. When I took over as Chief of Medical Services at Aster Medcity two years back, this was one of the issues and I had able support from Dr. Warrier. I can give you a simple example, it was the surgical site infections that was a battle we won. And we did not go for anything hitech. we knocked off 95%. From where we stood, we have come down to 1.

Dr. Anup R Warrier: We had about 15-20 every month, now it has come down to 1-3.

Dr John: Yes, we came down to 1. Regularly we are hitting it. The battle is not lost. We have to start with the basics. Education. Educating the public in a language they understand. That’s what we did. We took groups, nurses, paramedics, doctors, and gave them feedback. Retrain, retrain, give them feedback. And it took some time. One and a half years almost. But we did it. And that is what I think. I fully say that it is a challenging conquest which we are going to win. That’s what my final remark will be.

Dr Harish Pillai: Dr Anup, please, allow me to add to what Dr John just mentioned.

Dr. Anup R Warrier: Yes, Dr Harish

Dr Harish Pillai:In our group of hospitals in India, this institution- Aster Medcity receives the largest volume of international patients. Which adds one more dimension to the challenge of antimicrobial resistance. These groups of patients are mostly coming in from the Middle East and Africa. What he just was talking about, the 2-year cycle of surgical site infection rate, the same period also showed a quantum increase in the number of international patients. So, despite that surge, I think, what he said is something pretty good. In India, we also see this as a national challenge, because India is positioning itself as a medical value traveller’s destination to the world, as we discussed today unless Indian hospitals (especially those who are NABH accredited) get this act together; instead of being a solution to the world, we might become a headache. It’s critical that hospitals that cater to international and domestic patients have very robust AMR and AMS systems in place.

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