00:00 – Professor Malone-Lee: We learned to say sex does not do harm, and we understand why sex can stir it up…
00:20 – Melissa: Another question around this on the practical side of things – is it okay to have sex while
00:24 – you have a chronic bladder infection?
00:33 – Professor Malone-Lee: Now sex, when I was working on my own I used to tend to avoid to ask about sex simply
00:39 – because I hadn’t, you know, the pressure on the clinic and myself, I couldn’t get through the work. And then
00:45 – a girl who I started treating when she was a medical student, and then
00:49 – subsequently qualified, who’s worked with me on research and so on, she gave me an
00:57 – absolute bollocking for not asking about sex. And she was pretty imposing. So I then
01:03 – started asking about sex and I really regret not having addressed this before. And in fact,
01:13 – asking about sex has now become an astonishingly important part of our
01:20 – outcome measures. And when I’m treating patients, part of their homework is having sex.
01:28 – Now why should that be? Well first of all, we discovered that having sex can be painful and
01:35 – there can be a painful aftermath, but it doesn’t do harm. And if we’ve got people having sex we’re
01:44 – able to have them reporting, but it got better, and it got better, and it got better. And we use
01:49 – that as an outcome measure. Now the thing is, the other point is that if you’re sexually aroused
01:56 – you may not sense pain. So some people have sex and they don’t get pain and then the shit hits
02:02 – the fan afterwards. And it’s horrible, but learning from that we’ve learned to say
02:08 – sex does not do harm, it’s all right. And we understand why sex can stir it up,
02:18 – and the reason being, is that during sex you can perturb the cells of the bladder because of
02:24 – the pressures in the pelvis and all that kind of thing. And if you perturb the cells the
02:29 – bugs that are colonizing those cells will get a fright. They’ll wake up, start dividing. I mean if
02:34 – you give a bug a fright, it’ll just start dividing. That’s all they do. That’s their one
02:40 – reaction to adversity – divide. And as a result they produce a whole lot of progeny that then burst out
02:48 – and charge for safety. It’s like a murmuration of starlings really, a similar principle.
02:57 – So the way we address that, we’ll be ready for it. You up your dose if you have sex and then you
03:05 – would increase the concentration in your urine and that will deal with the acute flare.
03:10 – Melissa: Should you up the dose before sex if you can plan ahead (which is not often the case)?
03:15 – Professor Malone-Lee: That’s quite a good idea. Actually I’ll tell you something, one of the
03:20 – things I suffer from terribly is that a couple come in and I see her and I treat her and
03:30 – a few weeks later she writes and says dear prof, I’m pregnant. She got pregnant without my
03:36 – permission, damn it. But the thing is that people are so used to not becoming pregnant because
03:44 – they’ve got a chronic urine infection. You treat the urine infection and then become fertile and they
03:50 – become pregnant before you’ve got a chance to really get the whole thing under control.
03:55 – Melissa: That’s an interesting point that you just made though, the connection between infertility and chronic UTI. Is
04:00 – there something more that you can tell us about that?
04:02 – Professor Malone-Lee: Yes. We know that urinary tract infection, I’ll tell you it’s
04:10 – very interesting. Sorry, I keep saying it’s very interesting
04:12 – Melissa: You just have to make sure it’s interesting then.
04:15 – Professor Malone-Lee: That’s a good point! Well it’s very interesting to me.
04:20 – The urine infection is known to be a significant risk factor for miscarriage,
04:32 – premature birth,
04:36 – pyelonephritis, preeclampsia. We also suspect that as part of the miscarriage thing it may be a
04:44 – factor in infertility. And certainly I’ll tell you evolution tells us something about that because
04:51 – the normal woman, when she becomes pregnant starts shedding epithelial cells like there’s no tomorrow.
04:59 – Now it doesn’t make sense to start shedding cells when you’re pregnant because you’ve already got
05:05 – nutritional demands, so it strikes me that we have, that human beings have evolved to try and protect
05:12 – against infection during pregnancy in a big way. So we think that it plays an important
05:21 – role. The other thing is, I supervise all the pregnancies in our units and I’ve looked after
05:27 – 277 of them and the obstetricians tell us that our rate of miscarriage is too low
05:36 – for women who’ve got chronic urine infection. So in other words we might be doing something right
05:42 – and they’re looking into that. And the other thing is that I’ve had
05:49 – infertility doctors referring women to me because they thought that they had urine infection and
05:55 – it’s not uncommon. I mean, it’s informal this, but I’ve got this problem of people becoming
06:01 – pregnant when I hadn’t really wanted them to because we haven’t quite got it under control.
06:06 – Melissa: I assume they continue their treatment throughout their pregnancy?
06:12 – Professor Malone-Lee: Yeah that’s right. We were able to use Keflex and Nitrofurantoin incredibly safely in pregnancy. We’re
06:19 – very conscious of safety with pregnancy. So that I’ve got a rather obsessive approach to monitoring. I’m looking after them.
06:25 – Melissa: Would you ever take someone off their antibiotics if they reach
06:30 – the point where you would normally take someone off antibiotics, during pregnancy?
06:34 – Professor Malone-Lee: Not during pregnancy. I’m absolutely scared rigid of of a blow up during
06:41 – pregnancy because prematurity is not a funny thing at all.
06:48 – Melissa: Speaking of coming off the antibiotics, how many patients can come off at that point and then never have to go
06:53 – back on? Or do you think most people then have to try again and it takes a few times?
06:58 – Professor Malone-Lee: I don’t know the answer to that one and the reason being is that once we’ve got them off onto Hiprex.
07:03 – I give them a kiss and some instructions and wave bye bye with the option that they can contact me,
07:11 – you know if there are any problems. And I don’t know what it is. What we do say is that
07:19 – they will leave our care while still taking Hiprex with instructions on when they feel safe,
07:28 – you know, to decide on when they’re coming off. We give them, what we do say is a lifelong
07:35 – habit, you must have some antibiotics with you and you must self-medicate at the faintest hint
07:42 – of any trouble, whatever you do. And I talk about some woman who came back to me and once years ago
07:49 – and described how she was in the lunch queue at work and she thought, I think I might be starting
07:55 – a urine infection. So she took the antibiotics with her lunch she had them with her. That’s what
08:00 – we advise people to do. And we found that if you do that you find yourself in that three-day group.
08:07 – You can take it for a very short period of time and abort it. So we’re really keen on
08:13 – immediate self-medication on the faintest tint of any trouble.
08:18 – Melissa: Is the idea that you would take the antibiotics until your symptoms have disappeared?
08:24 – Professor Malone-Lee: Yes that’s right, So we say start it, and on our regimens there tends to be 12 hours between doses.
08:30 – So start it, you’ve then got 12 hours to decide whether you’re getting better, have another dose and usually
08:36 – it’s one or two days. We’ve got some people who take it for a week because they’re buggered if they’re ever going to risk
08:42 – going back to that. I understand, I don’t think that does any harm at all.
08:48 – Melissa: Maybe we can talk a little bit now about other side effects of antibiotics. Obviously
08:53 – a lot of people suffer from yeast infections or BV and have trouble taking long-term antibiotics
08:59 – because that can cause a lot of issues. What’s your approach there?
09:07 – Professor Malone-Lee: I have to say that in those days, going right back in the beginning of this century, that it was becoming
09:15 – clear to me that I was just not going to manage these patients without protracted antibiotics
09:22 – that were lasting much longer than i’d ever envisaged. And I was a terribly worried man and
09:28 – I remember sleepless nights out in the garden there just worrying, worrying, worrying about this.
09:34 – And so we adopted an obsessive approach to toxicity side effects and the such like.
09:41 – And our data scrutinized it meticulously. So in fact, when we had our crisis in 2015, or
09:50 – we were being looked we were able to produce the most remarkable data sets on side effects
09:56 – and consequences. No one was expecting it and so it continues so that we we’ve looked at side effects
10:03 – very, very carefully. Secondly, I’ve now treated well over over seven thousand patients. I’m not
10:09 – sure how it is seven thousand have gone through the stocks now. So what are we worried about?
10:16 – Well there are the idiosyncratic responses, side effects. So you’ve got people
10:21 – who are allergic and very often people come saying I’m allergic to penicillin. Most of
10:27 – those, we’ll ask them to do a skin test because people are often not allergic to penicillin
10:34 – and it’s better to get skin tested to know. Because if they say they’re allergic to
10:40 – penicillin, it can rather reduce our options, which can be a bit worrying. Resistance,
10:47 – this is the key point. We measure resistance and we keep measuring it all the time.
10:54 – If we extract microbes from someone’s urine when they first arrive
11:02 – and then when we see them after they’ve been on their their treatment for their first review visit,
11:09 – and extract microbes and measure the resistance, it will rise very slightly. The resistant measure that
11:16 – we use after that, it doesn’t alter at all. So the resistance profile of the bugs in your urine
11:24 – shifts slightly in response to the antibiotic that you’re prescribed and after that
11:32 – nothing tends to happen. So that the evidence is that we’re not creating resistance by using these
11:41 – long-term regimens. Now, the anatomy of that has to be just
11:48 – scrutinized in a great deal away, but I wasn’t terribly surprised to see that because
11:52 – Darwin told me that probably would be the case. It fits mathematically
12:01 – with Darwinian evolution for a whole lot of complex reasons I won’t go into. Provided
12:07 – we don’t start shuffling the antibiotics, that we strictly limit our prescribing
12:13 – to the first generation, where we start off and and stick at it through thick and thin.
12:19 – Right now the next thing is the bowels. Yes, antibiotics can alter the bowels but
12:25 – what I’ve learned over time, I thought about this a lot by watching the, you know, we feed birds out in our garden. And it’s very interesting to see the way different species of birds
12:36 – feed in different ways. And sometimes you want to go out and say listen you shits, the food’s there!
12:44 – You know, why are you feeding there? And also that they will go for different…
12:50 – For instance I’ve noticed recently that the starlings will go for little worms whereas none
12:56 – of the others want that and so on so forth. That’s very interesting. And it was in discussions of the
13:04 – gastroenterologists that I thought this might make some sense. Resistant starch are foods like
13:14 – potatoes have been cooked and cooled down. Potato salad, pasta cooked, cooled down, pasta salad
13:22 – and various pulses of one kind and another. Now the cold resistant starch, because the the starch
13:30 – in them is incompletely digested in the small intestine, so it goes through into the large bowel
13:37 – and there it provides food for the sort of bugs that you want.
13:44 – So if you feed them they will come. If you build it they will come, that comes from that film, but
13:50 – if you feed it they will come. So we’ve gone a big deal on using resistance starch.
13:58 – And I mean, once again this is just survey data, observational data where we can
14:06 – pick up that the bowel problems have reduced substantially. And we don’t encourage people
14:12 – to stop mucking around with probiotics and if they they want to have probiotics then have kefir.
14:21 – Partly because that acts in a similar way.
14:24 – Melissa: Last time you and I spoke you said that you had never tried kefir. Is that still the case?
14:28 – Professor Malone-Lee: Good point. Well I went off and tried it. God I rather like it. It’s just like yogurt, it’s really nice.
14:37 – I thought it was going to be absolutely ghastly. It was delicious, yeah it’s very very nice indeed.
14:43 – Right, now as to the vagina, there again we got into awful troubles really by
14:49 – treating candida with fungicides. Now the problem with this is that if you treat someone with a
14:56 – fungicide, it clears up, they feel much better, you stop the fungicide and back it comes again.
15:02 – So we’ve gone back to ecology, Darwin and the such like, and we’ve majored now in a big way
15:09 – on acidification of the vagina. So we encourage people to use boric acid or some other convenient
15:17 – acidification thing – they’re growing numbers of them. But to do it all the time.
15:25 – And in people who are acidifying their vagina, you’re creating an ecological circumstance where
15:32 – the candida can’t thrive and neither can the BV and all the others.
15:35 – Melissa: Does all the time mean using a suppository every night?
15:39 – Professor Malone-Lee: No, well pop the boric acid in twice a week, all right. And a lot of these
15:44 – things are like that, you don’t have to do it all the time. I’m very apprehensive about oral
15:51 – antifungal agents and these pessaries and so on. The fungicides, I just don’t think that they’re working
15:58 – and it comes back to this, the whole principle of re-wilding and ecology and so on. Let’s do it
16:05 – using our understanding of the selection of the bugs, all right. And of course
16:10 – the diagnosis of BV is based on measuring a relatively alkaline vagina. So you
1618 – know the acidification of the vagina, the BV is not going to thrive. So that’s the way
16:27 – we do with that now. The the other thing is that that there’s an awful lot out there about the way
16:35 – the microbiome of the bowel changes when you’re exposed to antibiotics. And children are given
16:41 – antibiotics, they’ve got a different microbiome and and so on. And then people build this up into doom,
16:48 – the end of the world. I honestly, I’m really not terribly convinced about that, the reason
16:55 – being is, there in the bladder we know that there are well over 450 different species.
17:02 – Loads more than that, so it’s a kind of soup of microbes of one kind and another.
17:10 – And if you perturb it, throw it up in there bring it down again, it will reorganize itself
17:16 – in a different form. So it’s no surprise that if you perturb it by putting someone on an antibiotic,
17:22 – throw it up in there bring it down again, when you measure it later it’ll be in a different form.
17:28 – There was a brilliant video I saw the other day that was suggested to me
17:34 – by someone on Twitter which it tells the effect of reintroducing wolves into Yellowstone
17:42 – Park. The video is brilliant, brilliant.
17:48 – And it once again brings back to this point that if you just let it be the the evolution
17:55 – and ecology will come together and recreate how things were. So I simply, I found it very hard
18:03 – to believe that you’re getting long-term catastrophic effects on the bowel. And the other
18:08 – thing that everyone forgets, is the bowel is full of microbes and we call antibiotics
18:16 – because they’re produced by microbes. They’re invented by microbes and what they do is, microbes
18:24 – produce antibiotics to kill off other bacteria so that they can have more to eat.
18:31 – So if I’m a bacterium producing an antibiotic to kill off my competitors,
18:36 – I must also produce a resistance factor or I’ll kill myself. So bacteria are constantly co-evolving
18:45 – antibiotics and resistance all the time and they’ve been around for 3.5 billion years
18:53 – squabbling, these microbes. So you would expect antibiotics and resistance factors
19:03 – to evolve long before humans even were thought about. So if you go into the
19:13 – Lechuguilla Caves, the Lechuguilla Cave, okay my editor says it’s cave, I thought it was caves, but anyway…
19:21 – A section of the Lechuguilla Cave in New Mexico was sealed
19:29 – off from the rest of the world for four million years. That’s a phenomena – four million years. Now,
19:35 – we humans evolved 120 000 years ago, so four million years. And so the biologists had
19:43 – this option and they found this sealed bubble, not been touched for four million years. So they put
19:50 – probes in and sucked out the contents and studied the microbiology. Now would you believe it, they
19:57 – grew from those caves bugs that were resistant to 14 or 18 different antibiotics including would you
20:06 – believe it, my cefalexin, which is a synthetic antibiotic invented by human beings. In fact
20:14 – if anyone’s sort of got any anxieties about cephalosporins, I can tell you that they were
20:19 – developed from Sardinian sewage effluent. So you can think of that when you’re
20:26 – eating Sardinian shit to get better. So the the point being is, that if you’ve got
20:36 – an environment where there are bacteria there will be antibiotics. And remember that we consist of 20,
20:47 – is it 20 trillion cells, and 20 trillion bacteria and those bacteria are living
20:55 – with us in a mutualist relationship and I assure you that they’re squabbling with each other
21:03 – and producing antibiotics and producing resistance. So it’s a much more
21:11 – subtle problem. And I think a lot of the AMR resistance, the AMR problem comes from people treating on culture.
21:19 – So you culture something, you’re convinced that’s the cause of the drug, the thing so
21:25 – you treat people based on the resistance of that. When you culture again, it’s inevitable –
21:32 – Darwin – that the bugs you grow will have a degree of resistance to the antibiotic you use.
21:37 – So you use a stronger one and a stronger one and a stronger one and I think we need
21:44 – better methods of studying causation to get around that.