Explaining high antimicrobial resistance in Asia

Elanco Animal Health’s chief medical officer speaks about antibiotic resistance in Asia, and what is contributing to the problem
An interview with
Chief Medical Officer at Elanco Animal Health

Elanco Animal Health’s chief medical officer speaks about antibiotic resistance in Asia, and what is contributing to the problem

Asia is home to three-fifths of the world’s population, and the bulk of these 4.6 billion people live in developing countries. Given the widespread use of antimicrobials (including mainly antibiotics) across the continent, antibiotic resistance has emerged as one of the key health challenges here, with serious ramifications for society.

In the first part of this interview, Unravel’s Siddharth Poddar and Shivaji Bagchi speak with Shabbir Simjee, Chief Medical Officer at Elanco Animal Health, about why antimicrobial resistance (AMR) is high across Asia, the role played by generics, and poor regulation.

Unravel: How would you explain AMR to a layperson?

Shabbir Simjee: There are two aspects to AMR. You’ve got the veterinary agricultural aspect and you have the human aspect. As much as people like to make these two interchangeable, there is increasing evidence to suggest that resistance doesn’t really transfer from animal bacteria into human bacteria. The concern really is whether you have resistant bacteria going through the food chain – and these are predominantly food borne bacteria like salmonella and campylobacter. And if they do, will they cause us infections so severe that an antibiotic will be needed? And then, will that antibiotic fail because of resistance?

However, that isn’t to say that resistance in bacteria specific for causing infections in animals is not increasing as well. In the veterinary sector, in my opinion, we’re probably about 10 to 15 years behind where resistance is in humans. Resistance in the human sector is astonishingly high, especially within hospital settings.

What we tend to see in humans is that in community acquired infections, resistance tends to be lower. However, the bacteria are more virulent. In contrast, in hospital acquired infections, virulence of the bacteria is lower. However, they tend to carry more resistance genes.

Therefore, infections in the community tend to be easier to treat. But when you start looking at infections in a hospital setting, the bacteria are commonly less virulent. They don’t have the necessary gene that could easily colonise a human. However, at the expense of not having virulent genes they carry antibiotic resistance genes which are probably more harmful to the patient. As a result, we tend to see a lot more resistance within hospital settings. This is a phenomenon not limited to Asia, but is seen across the world.

Unravel: Is there a relationship between the veterinary side and the human side in terms of resistance to antibiotics?

Dr Simjee: Food-borne pathogens, predominantly salmonella and campylobacter, go through the food chain and cause human infections. However, it is my view that the infections stem from poor hygiene more than anything else. Wet markets, hand-to-mouth contact without washing hands, poor hygiene in kitchens where people may use the same chopping board for meats and vegetables, and not washing utensils in between – these factors are probably driving infections more than anything else. If we look at the cooking habits across Asia, it isn’t like Europe. Everything is cooked very well in Asia; and it’s all deep fried if nothing else. That would tend to kill anything and everything that’s on the meat. What’s causing the infections is probably bugs that are on the meat pre-cooking, and poor kitchen hygiene and so on.

Food-borne pathogens go through the food chain and cause human infections. However, it is my view that the infections stem from poor hygiene more than anything else.

To track what resistance maybe present in bacteria from animals we have typically monitored for resistance in two commensal bacteria from animals, E. coli and Enterococcus spp. There was a long-standing belief that these bacterial species may also be going through the food chain and causing human infections. However, there is now increasing evidence that these bacteria do not go through the food chain, nor do they transfer their resistance while they’re transitioning going through humans, and therefore play no role in human infections either directly or by virtue of resistance gene transfer. This is especially true for animal commensal E. coli.

Unravel: Why is AMR relatively higher in Asia?

Dr Simjee: There are a few reasons why this is the case. The main reason we tend to see higher resistance in Asia is because of the ready availability of antibiotics over the counter across most countries. This results in a lot of people self-medicating and consuming far more antibiotics than they should, or than needed. For example, many people in Asia won’t go to a physician if they’ve got a chest infection. A chest infection is typically a viral infection but they’ll go directly to a pharmacy. Now, most of these pharmacies are small shops run by non-qualified pharmacists. They will likely just give an antibiotic which isn’t necessarily needed. That’s the biggest problem.

We need to understand that all antibiotics are not the same. Some antibiotics are for enteric infections, some for respiratory infections and so on. Taking a wrong antibiotic has two impacts. First, it won’t help address infection, and second, it puts selective pressure on the development of resistance. 

Another important factor is the availability of either fake or generic drugs. Fake drugs are an issue for obvious reasons, so let’s focus more on the generics. A lot of the generic drugs are not bio-equivalent to the same drug from a branded company – which means the amount of actual active antibiotic differs between what should essentially be the same drug from different companies. And additionally, their registration process doesn’t include the same level of scrutiny and testing. So, despite the packaging stating a particular composition, in reality the composition of the drug may be different. If you purchase a branded drug, you’re guaranteed of the composition but that is simply not the case with most generics. Quite plainly, these generics often do not get rid of the infection; more importantly, they put selective pressure on the bug to actually develop resistance.

On the topic of over the counter, we’ve got the carbapenems – a very potent class of antibiotics. These drugs are supposed to be strictly limited to hospital use and shouldn’t be used outside of hospital settings. However, a number of pharmacies across Asian countries have them on the shelves and they are sold easily without any prescriptions, despite their packaging explicitly stating they shouldn’t be sold over the counter. This doesn’t help the cause when we are desperately trying to limit the use of antibiotics, and you’ve got these extremely potent antibiotics being sold over the counter. Carbapenems are typically used as last resort antibiotics and if ‘illegal’ community access occurs, this can result in a quicker rate of resistance development to this potent class of antibiotic. Ultimately, we will lose efficacy of these antibiotics and as of now there is nothing on the R&D horizon to replace these antibiotics.

These are some of the biggest drivers for higher AMR across both Asia, and even Latin America.

If you purchase a branded drug, you're guaranteed of the composition but that is simply not the case with most generics. Quite plainly, these generics often do not get rid of the infection; more importantly, they put selective pressure on the bug to actually develop resistance.

Look, antibiotic resistance genes have been around for thousands of years, if not hundreds of thousands. The only thing that has actually changed in the recent past is that the excessive use of antibiotics—predominantly in the human sector—has just helped expand and propagate that resistance among bacteria.

Unravel: Why does it happen to this degree in Asia?

Dr Simjee: The trouble is we are not actually sure how many people are infected with drug resistant infections across Asia, especially if it’s in the smaller towns and villages – because those instances probably go unreported or undocumented. I think one of the problems we’ve seen in Asia is that the cost of going to the hospital, or going to see a physician, is very high relative to incomes. As such, a lot of these people can’t afford to go to hospitals for treatment.

Another factor to bear in mind is that resistance to antibiotics will not always be the same globally. What I mean is that we cannot say you’ve got more resistance to penicillin in Asia and Latin America as compared to Europe. A lot of the differences in resistance are dependent on the drugs that are available in the country and the region. Across Europe you might see a trend towards resistance to some of the more expensive drugs, whereas in Asia, you might see trends in resistance towards the cheaper and more readily available drugs.

Again, we see the importance of the cost factor in all of this.

Unravel: Can you explain this cost factor with an example?

Dr Simjee: Although I was born in the UK and live here, my background is from India and I have been there many times. I have seen some hospitals in Delhi, Mumbai and Chennai. You’ve got hospitals catering to medical tourism. They’re expensive but they’ve got the best equipment, the latest and most expensive drugs. However, they can only cater to tiny, rich section of the population in India.

It’s a similar story across much of Asia. The majority of people in most developing countries in Asia will go to a local hospital or a local doctor. In Indian villages, for example, there are not too many practising doctors. A lot of villages don’t actually have doctors, they have what are called compounders. They are just drug makers mixing concoctions and giving them to patients hoping they’ll do the job. It’s only when the patient becomes severely ill that they may go to a larger town and visit a hospital or a doctor. Keep in mind that all of this costs a lot of money for a poor person.

And I’ve taken India as an example but if you look across Asia, we see the same problem, including in China, which also doesn’t have enough doctors to cover that large a population.

The second part of this interview can be read here.

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Chief Medical Officer at Elanco Animal Health

Professor Shabbir Simjee is chief medical officer at Elanco Animal Health and holds global responsibilities for its antimicrobial portfolio, from discovery through to post approval. Prior to this, he worked at the US FDA for three years at the Center for Veterinary Medicine, specifically looking at gene transfers between animal and human pathogens. Dr Simjee is past-chair of the VetPath program, a pan-European AMR monitoring programme, and past co-chair of the CLSI veterinary antimicrobial susceptibility testing sub-committee.

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