CASE NOTES 1: ANTIBIOTICS
RADIO 4
TUESDAY 06/04/04 2100-2130
PRESENTER: MARK PORTER
REPORTER: TRISH MACNAIR
CONTRIBUTORS:
MARK WILCOX
DAVID LIVERMORE
TONY FIELDS
KEITH GIRLING
STIG BENGMARK
VANYA GANT
PRODUCER: HELEN SHARP
PORTER
Hello. The average British man will take around 50 courses of antibiotics throughout his life - a woman closer to 70. Antibiotic use is falling - but is it too little too late? Decades of overuse, not just by doctors - but by vets, dentists and the farming industry too - have encouraged the growth of a new breed of antibiotic resistant superbugs - like the infamous MRSA - with some experts predicting that the most widely used antibiotics could become useless within a decade.
CLIP
Where we perhaps have our greatest problems are with hospital bacteria that give infections in intensive care patients. And some of those are resistant to practically everything we now have. It's there that we're closest to the end of antibiotics.
PORTER
But it's not just resistance that's worrying doctors - heavy antibiotic use has been linked with other problems too - including breast cancer, asthma and inflammatory bowel disease. The exact nature of these links remains unclear, but one theory is that it's something to do with the effect that antibiotics have on the billions of bacteria that normally colonise the human bowel. The average adult carries around 2 kilos of these so called "healthy bacteria" - that's the equivalent of two bags of sugar - and I'll be finding out how encouraging their growth using something that's probacteria - probiotics - has almost eliminated post operative infections in one transplant unit. What else could probiotics do for us?
My guest today is Mark Wilcox, Director of Infection Control at Leeds Teaching Hospitals.
Mark, the average person is getting something like one course of antibiotics every year. We are becoming more careful with them now though aren't we?
WILCOX
Yes we certainly have reduced the use of antibiotics in the community, so GPs are prescribing less antibiotics. But there isn't good evidence that we're using at all less antibiotics in the hospital setting.
PORTER
Perhaps we should start off by saying or explaining exactly what an antibiotic is.
WILCOX
An antibiotic is a drug or a chemical, usually - well originally it used to be produced actually by other bugs, other bacteria, but now usually the pharmaceutical companies have become clever and they get these original drugs and manipulate them to make these new better antibiotics.
PORTER
So they're killing bacteria or stopping bacteria growing. How do they actually do that?
WILCOX
There's a variety of ways that antibiotics can work, some of them will actually work by damaging the wall, the coat, around the bacterium. Others will get inside and actually destroy the assembly line - the protein, building blocks of life factory, where all the DNA works and so on.
PORTER
What sort of bacteria do they kill, do antibiotics have quite limited uses, they don't kill all types of bacteria do they?
WILCOX
Well strictly speaking antibiotics work against bacteria, so they don't work against yeasts, they don't work against viruses, they work against bacteria. And there are two broad families of bacteria and some antibiotics work well against one family and some against another family.
PORTER
And that depends presumably on the individual makeup of the bacteria - they function in slightly different ways do they?
WILCOX
Yes the basic difference between these two families of bacteria is in the wall, in the coat of the bacterium, and some antibiotics need to get through that coat to work and if they're not designed correctly to get through that coat they won't tend to work at all against that particular family of bacteria.
PORTER
Well of course one of the other problems is antibiotic resistance, it's one of the major challenges facing modern medicine now, particularly hospital medicine where bacteria like methicillin resistant staphylococcus aureus, that's MRSA - which is immune to a wide range of antibiotics - are a growing problem. Official figures suggest around a thousand people died last year from MRSA infection but the real figure may be closer to five thousand.
David Livermore is Director of the Antibiotic Laboratory at the Health Protection Agency and I asked him how bacteria like MRSA become resistant.
LIVERMORE
It varies with the type of resistance, sometimes a gene gets transferred from one type of bacterium to another and that's what happened in the original emergence of MRSA. In other cases it's a case of mutation - when the organism is reproducing some mistake occurs as its DNA is copies, as its genetic information is copied, and that mistake leads to a change which makes the bacteria more resistant. Most of the MRSA that we see are just two strains, which have been highly successful from spreading from patient to patient. The earliest strains of MRSA that we had going right back into the 1970s were not very good at transferring from patient to patient but the recent ones, the ones we call epidemic 15 and 16, have been very efficient at transfer.
PORTER
So antibiotic overuse itself won't create a resistant "superbug" in inverted commas, but it can single them out, it can encourage their growth, presumably by getting rid of other bacteria that are susceptible?
LIVERMORE
Yes. If an antibiotic actually caused resistance it would be causing mutation, it would never get a licence. However, as we use antibiotics - this is the critical thing - we kill all the sensitive bacteria and the resistant ones survive. So we provide what in Darwinian terms would be called a selection pressure and the more we use antibiotics the greater that selection pressure, the more we select out resistant bacteria.
PORTER
Now in a community as a GP if I come across a urinary tract infection that's caused by a resistant bacteria I can just switch to another form of antibiotics, it's quite easy. But what happens when you're dealing with things like MRSA, that are a bit harder, or bugs that are resistant to lots of lots of different types of antibiotics, could you see a day - or are we there already - where we've got bacteria that don't respond to any antibiotics?
LIVERMORE
Well in the case of MRSA we have got antibiotics left and there are new antibiotics coming along. So with MRSA we do have treatment options and we have a growing list of new treatment options. Where we perhaps have our greatest problems are with a group of organisms called Acinetobacter and Pseudomonas. These are mostly hospital bacteria that give infections in intensive care patients who are really very, very vulnerable to infection. And some of those are resistant to practically everything we now have. Usually when you rummage about you can find some old antibiotic that still retains a moderate degree of activity and which can be used but it's there that we're closest to the end of antibiotics.
PORTER
And what sort of effects are these infections having on the patients that get them?
LIVERMORE
The patients who get them are often very seriously ill patients anyway, who've got multiple underlying problems. It's often very, very hard to be certain how much the infection really contributes to the patient's ultimate fate but clearly having an infection which is very, very difficult to treat can't improve your chances of recovery.
PORTER
What happens to somebody who gets a wound infection - a perfectly well person who goes in, let's say, for that hernia repair and they get a MRSA infection in the wound, what's the outlook for them?
LIVERMORE
The outlook is really pretty good. MRSA infections, on the whole, are treatable. The worst cases that one does hear about are commonly bone and joint infections where if somebody's having a replacement hip put in and that becomes infected with MRSA during the surgery then trying to cure that infection is very hard because the bacteria start to grow as a film on the artificial hip joint and trying to cure that without removing the replacement hip is extremely difficult.
PORTER
An all too familiar scenario for Tony Fields, who caught MRSA after surgery to repair a broken thigh bone two years ago. He spent three weeks in an accident and emergency department and four on a specialist orthopaedic ward. But then he learnt he was infected just before he was due to go home. He was reassured that the antibiotics he had been given had got rid of the MRSA, and that he'd "get over it". Sadly that wasn't to be - ongoing infection and two further attempts to surgically eliminate it, have left him with no hip joint and the upper two thirds of his thigh bone missing. Amazingly he can still walk but only with crutches. His experiences, and those of fellow patients infected with MRSA, led to him setting up MRSA Support - a group for those infected. He believes he caught the infection fairly soon after being admitted.
FIELDS
I'm sure that I picked it up in that A&E hospital, in the ward, when I needed the bedpan and the nurse refused to help to clean me and not being able to wear pyjamas and not being cleaned I really had no option but to literally lie back on the sheets and my buttocks were very sore, in fact they were weeping with the soreness and I'm sure that's where my MRSA came from. Perhaps from myself but possibly airborne from other patients who insisted on walking around the ward in a fairly unclean state.
PORTER
Was the ward itself clean did you think, did you notice?
FIELDS
It was not clean. It didn't worry me because I didn't know anything about MRSA, I hadn't got a clue.
PORTER
What about doctors and nurses and other people attending to you, washing their hands and things?
FIELDS
They would wear gloves but they appeared on the scene with gloves on, so one couldn't say whether they...
PORTER
Whether they were a new pair of gloves or not.
FIELDS
Indeed, indeed.
PORTER
What advice would you give to somebody who's going into hospital who's worried about MRSA?
FIELDS
For routine operations the advice is quite clear. For a few days, perhaps a week, before going into hospital wash, bathe with an antibacterial soap, so that you in fact are clean and it's not on your skin. Get into the hospital and watch, make sure you're not touched by another patient or by a nurse who hasn't washed their hands as an immediate thing before coming to you. And the hand washing procedure must be adopted before putting gloves on and indeed immediately after taking gloves off.
PORTER
I've never been asked to wash my hands by a patient in 20 years, I can understand why - I can understand why they should ask me - but I've never actually been asked, it's an interesting thing that people don't. They don't like questioning a doctor …
FIELDS
Indeed no that's true and I know two stories of our members who have pointed out to a consultant that their hands have not been washed and their tie is hanging over the patient and it hasn't gone down well, I must say that, it hasn't gone down well but it has been observed.
PORTER
Tony Fields, chair of MRSA Support.
You're listening to a Case Notes special on antibiotics. I'm Dr Mark Porter and my guest is Dr Mark Wilcox, a specialist in infection control.
Mark, MRSA is a particular problem in British hospitals, we don't compare very favourably with other hospitals in the developed world do we.
WILCOX
No unfortunately we don't, we're fairly near the top of the infamous league table in terms of the proportion of all staphaureas, because that's what MRSA is, the proportion of all staphaureas that are MRSA as opposed to being MSSA - the susceptible sort. In the UK about 40% or 50% of all the MRSA that get into blood, all the staphaureas that get into blood rather, are MRSA. In other countries it tends to be a bit less than that.
PORTER
Is it something to do with the NHS, is it something to do with our hospitals, is it - as Tony Fields was suggesting - simply dirty hands and dirty wards or are we particularly heavy antibiotic users - why have we got a problem here?
WILCOX
I think it's for a variety of reasons. I don't think there's actually very good evidence at all to support the fact that a dirty hospital is a cause of MRSA if you like. MRSA doesn't tend to fly through the air, it can do but that tends to be the exception. So MRSA spreads usually by people touching one another or touching a surface contaminating that surface and then somebody else coming along and touching the surface. So certainly that - the spread of MRSA is important. And if your hospital is running at 100% bed occupancy, in other words as soon as one bed is emptied it's filled almost immediately, then the staff tend to be working harder, they have less time to carry out what should be perfect practice - washing hands each and every time, which may be 20, 30, 40 times a day. It only takes one of those 30, 40 times not to do what they're meant to do and the organism may be spread. The other important thing, as well as being a hospital working too hard, is that if we haven't got enough rooms to isolate patients who we know have got MRSA then we've literally got MRSA in one bed next to another patient without it and that's very hard to prevent MRSA spreading because of the reasons I've just said.
PORTER
Are we making inroads do you think?
WILCOX
If you look at the figures for how MRSA is spread in the UK it has plateaued largely in the last two or three years. Now that either means we've reached a natural plateau where the MRSA is happy at this level in nature, as it were, or we're actually starting to make inroads, one or the other, and only time will tell which of those two is true. But certainly a lot of things have happened in the last two or three years, particularly now hospitals have to publish their MRSA rates, so we can compare one hospital with another and we couldn't do that before.
PORTER
Do you think we're facing a post-antibiotic era? I mean these are amazing drugs, when they arrived in the '40s and '50s they really transformed the management of - people were dying of quite minor infections before then or infections that we would regard as minor today. Can you see us running out of antibiotics and having to find a new way of tackling bacterial infection?
WILCOX
Well hopefully not in my lifetime and I really can't see us running out of antibiotics. David Livermore talked earlier about certain bugs that are seen in patients on an intensive care unit. Just let's put that in perspective. A big hospital will have about 1,000 beds, of those 1,000 beds 10 of them will be the intensive care unit and of the patients in those 10 beds maybe one or two a month will get these sorts of multi-resistant bugs where we haven't got an antibiotic to treat them. So it's a very, very small proportion of all the patients. That's no consolation if you're one of those patients but it is a very, very small proportion. And we are developing new drugs all the time which are just about keeping pace with the prevalent organisms - the big hitting organisms - but these small niche organisms such as Acinetobacter, which David Livermore referred to, those are the problem areas where the outlook is bleak for those but that's the exception rather than the rule.
PORTER
Mark, thanks very much for now. Well an alternative approach to preventing infection is to work with bacteria, rather than fight against them. New research suggests that encouraging the growth of the billions of healthy bacteria that normally live in the bowel can reduce infections in hospital patients - including the most vulnerable ones in intensive care. Trish Macnair reports.
ACTUALITY - QUEEN'S MEDICAL CENTRE, NOTTINGHAM
Okay Adam, how are we getting on here, we're on day 15 now aren't we?
Yeah not too bad.
MACNAIR
Here on the intensive care unit at Queen's Medical Centre in Nottingham, consultant Keith Girling knows only too well the risk of infection in very sick patients.
GIRLING
The vast majority of our patients are on a life support machine, a breathing machine, for the majority of their stay here. They're exposed to a number of infections that are in the unit and most of their protective mechanisms for dealing with those infections are removed by the mixture of drugs that we're using by having a plastic tube in the windpipe and not being able to deep breathe, not being able to cough for themselves and up to approximately a third of the patients with mechanical ventilation would acquire a hospital acquired infection, ventilated associated pneumonia, during their stay on the intensive care unit here.
MACNAIR
These sort of infections can be very dangerous, increasing the risk of dying on the intensive care unit by up to 50%. And if the bacteria are resistant to treatment the risk may increase by as much as 76%. It's not surprising that powerful antibiotics are frequently used. But many people have begun to wonder whether there isn't a more effective way to prevent infection in the first place.
Stig Bengmark, a professor of surgery from Lund, Sweden and currently honorary visiting professor at University College London, was appalled to find that even when antibiotics were used, between 50 and 80% of his patients developed infection after surgery. He decided to investigate the problem further.
BENGMARK
I was doing extensive liver operations, we call them liver insections, and at one stage I asked a young doctor to review the results of the last eight liver insections. At that time we had the principle of supplying antibiotics for five days with the hope to prevent infections. He came back and told me one-third of the patients have not received the antibiotics and the surprising result was that this third had no infections and all the infections were in those who had received the antibiotics.
MACNAIR
This made Professor Bengmark wonder whether the antibiotics were doing more harm than good, somehow damaging the patients' immune system. His attention focussed on the millions and millions of bacteria we all have in our gut. Most of us go about our lives completely unaware that in our intestines there are up to 500 different species of bacteria. We still don't know what many of these bacteria are but some, particularly types called lactobacilli and bifidobacilli, play a vital role to keep us healthy. Dr Vanya Gant, Clinical Director for Infection at University College Hospital, London explains,
GANT
Some good bacteria break food constituents down into short chain fatty acids and we know that these molecules are essential for the healthy gut to survive and thrive and work normally. And these substances do not exist in normal foods. We need the bacteria to produce them for us.
MACNAIR
So what happens to these friendly bacteria when antibiotics are used. Dr Gant again.
GANT
Antibiotics can be and are lifesaving on occasions. Most of the time they do not help at all and we must not forget that if you take an antibiotic it's not only the bad bacteria that go, it's all the good ones as well and it can take weeks, if not months, for your normal gut population to re-establish itself after you've had even a short course of antibiotics.
MACNAIR
Studies have shown that after antibiotic therapy the first thing that happens is that less friendly, or bad bacteria return and start misbehaving, causing infection. So Professor Bengmark decided to try a different approach. He started treating his patients with a supplement containing a dose of friendly bacteria, called probiotics, as well as a dose of fibre, called a prebiotic, which provides an essential food supply for the bacteria. Together probiotics and prebiotics are now called symbiotics.
BENGMARK
When we gave a combination of one lactobacillus - a lactobacillus plantarum - and one fibre, which was an old fibre, did we reduce the sepsis rate to 13% - one three. And then we continued and introduced another formula which contained four lactic acid bacteria and four fibres and we gave 40 billion per day of these lactic acid bacteria plus 10 gram of fibre and in this study only one of 33 patients - which is 3% developed septic manifestations. In practical terms we had eliminated septic manifestations after liver transplantation.
MACNAIR
The results of Professor Bengmarks' work have so impressed Keith Girling in Nottingham that he is now testing what many doctors still regard as a rather fringe treatment on his patients in intensive care.
GIRLING
I don't think 10 years ago we'd have had any idea that this was a line we were taking. What we're doing at the moment is randomising all the patients that come into the intensive care unit here at Queen's into one of two groups - and one group is just getting a fibre additive to the feed that they're getting placed through a tube that's in the stomach and the other group are getting a fibre feed supplemented with lactobacillus symbiotic preparation.
MACNAIR
According to Dr Gant, the evidence for symbiotics is growing.
GANT
We have evidence that probiotic bacteria can assist in wound healing, can lower rates of opportunistic infections with the other rather more harmful bacteria. We have evidence that even in the context of things like bone marrow transplantation it would appear that if you keep a very healthy probiotic bacterial population you tend to suffer from less complications.
MACNAIR
Looking after the gut bacteria could be life saving for seriously ill patients but the research also has an important message for the rest of us. We need a regular supply of lactobacilli. However, before you reach for your daily dose of live yoghurt, that might not be the best way to get the lactobacilli you need.
BENGMARK
The yoghurt bacteria they will most likely not survive the acidity in the stomach or the bile acid content in the small intestine and they're largely useless [indistinct words]. What I'm talking about are specific lactic acid bacteria which grow on plants, we should try to eat more like our forefathers - eat much more of fruits and vegetables and non-processed food. And if we eat them we will also get lactic acid bacteria.
PORTER
Trish Macnair there talking to Professor Stig Bengmark.
Mark, the Professor suggests that encouraging health bacteria requires a bit more than drinking yoghurt - you also need to nurture the bacteria with something to live on?
WILCOX
Yes the - we heard that the normal gut has about 500 different species of bacteria, add to that perhaps double that number of viruses that actually live in our gut, so it's a very, very complex situation. If you simply drink or eat one bacterium which you've been given - a probiotic - the chances that that one bacterium can have a significant effect on this huge complex ecology in the gut, consisting of hundreds and hundreds of different species is very, very small. If, however, at the same time you were to give a bacterium or two or three of them and give a foodstuff which can not only affect the two or three that you're giving but perhaps 10 or 20 or hundreds of the other species that are there then you can see that that's got a much greater chance of significantly affecting the gut ecology rather than just the needle in a haystack approach of throwing one bacterium at hundreds of others.
PORTER
So what about the probiotic drinks that you can buy from supermarkets and pharmacies - I mean basically are you saying that without prebiotics as well, without something to nurture those bacteria, they're basically a waste of time?
WILCOX
It's difficult to be so dismissive but I'd turn it round and unfortunately - not unfortunately, fortunately I'm brought up to rely on evidence of effectiveness and certainly, for example, we're not allowed to use antibiotics unless we've proven that they work, these sorts of drinks that you're talking about have very little proof attached to them. So I think the chances of them doing anything harmful is very small, that's the good news, but where's the evidence that they actually do things that are good for you? And I'm afraid that evidence is just lacking in most, if not all, of these over-the-counter probiotics that we're talking about. My worry is that people are perhaps wasting their money and could divert it into increasing the quality of their diet by increasing more fruit and vegetables for example instead of spending them on these probiotics.
PORTER
So where is the evidence, do we have good evidence that probiotics do help things, other than what we've just heard?
WILCOX
Probably the best evidence that probiotics can work is in the context of diarrhoea in childhood, some sorts of gastroenteritis and that's a very specific situation and it doesn't mean it can work against all sorts of diarrhoea. But there is some evidence there that they can prevent gastroenteritis occurring as frequently in babies given these probiotics as opposed to babies given a placebo. Outside of that setting I'm afraid the evidence is very scant that they actually work at all and I think the other point to make here is that giving a probiotic to you or to me won't necessarily have the same effect because your gut ecology is likely to be different to mine. Plus my gut ecology today may be different next week, dependent on the foodstuffs that I'm eating. We can quite easily imagine that if you were to have a curry your gut bacteria may look very different the next day as opposed to if you simple have a bowl of porridge.
PORTER
Mark that's all we have time for I'm afraid. Dr Mark Wilcox thank you very much.
If you want more information on anything we have discussed then do call our Action Line, that's 0800 044 044, and for useful contacts try visiting the website at bbc.co.uk/radio4 - where you can also listen to the programme again.
Next week I'll be leaving the relative quiet of the studio and coming to you from the busy accident and emergency department at Whipps Cross University Hospital in London for a behind the scenes look at the world of ER.
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