00:00 – Dr. Hlavinka: We’re dealing with some very, very ancient organisms that have a real keen survival mechanism and they’re tough to get rid of.
00:25 – Melissa: So let’s move on to a discussion more about the urinary microbiome and the yeast or BV connection
00:31 – with recurrent UTI. Maybe you can explain a little bit more about the urinary microbiome.
00:37 – Now that we know that it exists is there a way that we can actively support that?
00:42 – Dr. Hlavinka: We do know now that there is a urinary microbiome and there’s the normal, there’s the quasi-normal
00:50 – and then there’s the abnormal. And you can have organisms that are clearly pathogenic and live in
00:56 – the environment and cause no problems whatsoever, then you can have organisms that are clearly
01:03 – commensal, or harmless quote unquote and in many patients cause severe harm, in a given patient who may be
01:10 – susceptible to that microbe. By and by there are rules but I have found that with patients and
01:19 – next generation sequencing and identification and treatment that I didn’t get to make the rules, they
01:26 – do. And what I thought were the rules from what I learned in microbiology and infectious disease
01:32 – therapy and pharmacology were wrong because it just doesn’t work that way. I think that we
01:39 – have to be adaptive as providers to these lessons, just like the microbes are adaptive in
01:47 – keeping in our bodies and causing havoc. So that’s the problem. We’re dealing with some very, very
01:53 – ancient organisms that have a real keen survival mechanism and and they’re tough to get rid of.
02:02 – So discovering that first is the most important thing and absolutely the next question is do
02:08 – antibiotics impact the bladder microbiome. I don’t need to tell this group the
02:14 – cascade of events that happens with their first UTI treatment. I hear these stories that
02:21 – end up being two or three years long after that for the patient so the bottom line is that
02:28 – you do want to not alter that microbiome, you do want to take alternative therapies if you can, you
02:33 – do want to get rid of an infection in the easiest way. But when it does happen you want to eradicate
02:37 – it because you don’t want to have that become resistant and you don’t want to have it cause
02:42 – more symptomatic infections. So when you do get an antibiotic you’re always fighting two battles,
02:50 – alteration in the microbiome and getting rid of the acute infection. There’s like two
02:56 – swords I have to have and I’m not very good at fencing anyway. So the bottom line is
03:02 – it’s the scourge of my existence when that doesn’t work. When it works I get to be the hero and
03:08 – pat myself on both shoulders, but when it doesn’t then the patient and I have to sit
03:14 – there with a chagrined look on both of our faces and decide what to do next.
03:17 – Melissa: So in terms of the urinary microbiome, is it linked to the vaginal microbiome? And then the question again
03:24 – is, can probiotics help in either location?
03:28 – Dr. Hlavinka: So if we’re going to get into probiotic. I mentioned them before. I’m a firm believer in probiotics. I was very fortunate to meet a provider about 20 years ago
03:40 – who was a GI doc who was treating C. difficile overgrowth and and symptomatic C. difficile which is
03:49 – clustering difficile and a really terrible antibiotic complication that causes severe
03:56 – diarrhea and can even cause bleeding and death in the worst case. And many people have fear of that
04:02 – and for a lot of providers the fear of creating C. difficile is the reason why they don’t treat
04:08 – any infections aggressively and they won’t tell you that but I will tell you that.
04:12 – I’m not afraid of it. I’m not afraid of that because I got aggressive with probiotics.
04:18 – What you buy over the counter typically, or the doctors recommend is not at all adequate.
04:24 – You need on a daily basis we need between 20 and 60 billion
04:31 – colonies of microbes in our gut – new ones. And it’s very difficult to get that with diet. Now
04:39 – if you have enhanced kimchi and things like that where somebody’s actually fermenting and creating
04:46 – a product, a natural product, that does have it, but even then you don’t know what you’re getting and
04:50 – you don’t know what organisms. A good quality natural probiotic with 10 organisms and at least
04:59 – 20 billion per capsule that is shelf-stable so you don’t have to worry about refrigerating it. Enteric
05:04 – coated so your stomach acid doesn’t chew it up. That’s the other thing, if you drink these liquids
05:08 – your stomach acid chews it up, and you certainly don’t take it with an hour or two of taking an
05:12 – antibiotic because the antibiotic will kill it all. So a lot of really simple practical things about
05:19 – probiotic use, we don’t do. And I will tell you, the infectious disease doctors
05:24 – just wagged their finger at me and told me what I was going to experience when I did Microgen and
05:28 – and all the next generation sequencing treatments and multiple antibiotics. I have not
05:33 – had a single case knock on wood of C. difficile. In fact I don’t even think I’ve had
05:41 – any antibiotic related complications, all right. And that is absolutely rare and it’s because my
05:47 – patients know when they come to me for recurrent UTIs, part of the prescription is not just here’s
05:52 – your antibiotic, take it and come see me in two weeks, let’s check another culture. It’s, here’s
05:57 – the program for getting rid of your infections, and getting on probiotics yesterday is going to be the
06:02 – most important thing. And so how does it alter it? Well you create,
06:09 – as I said, that fight between normal and abnormal microbiome and you what you do is you tilt the
06:15 – scales more toward the normal microbiome which enhances the immune system. What we’re learning is that
06:20 – the gut and its microbiome have tremendous amounts of intelligence and there’s actually
06:27 – a brain gut connection in the microbiome. So the bottom line is being very aggressive with
06:33 – probiotics has been absolutely as essential as my incorporation of next generation sequencing
06:40 – into my therapy. And keeping that healthy and its impact on the immune system has a profound effect on my impact on patients with infections.
06:54 – Melissa: Do you also recommend suppository probiotics?
06:57 – Dr. Hlavinka: I’d say that that is different. If we can do it by oral probiotics I prefer that because it’s much
07:02 – easier and simpler. It’s sometimes hard to get it right and I’ve actually made things worse. I tend
07:08 – to want to stay away from the vagina when there’s antibiotics because I’ve seen these circumstances
07:13 – where this and that chemical compound and refresh and replenish and natural this and
07:18 – that and and then all of a sudden who knows what the chemical environment is like in the vagina.
07:24 – Restoring a homeostatic level and normal vaginal chemical and microbial environment
07:35 – to me is the most important thing to prevent the next infection. And so many times what we’re
07:39 – doing is just kicking the can down the road or disturbing that further and I prefer
07:44 – to stay away and do simple things, but yes I have used all of those, I’ve used all of those when necessary.
07:49 – Melissa: Do you think long-term antibiotic use actually destroys the bladder microbiome
07:54 – entirely, and can you ever overcome that if you have been down that road?
08:00 – Dr. Hlavinka: That’s a very good question. That’s controversial. At best I would say that it depends on the pace
08:07 – and severity of infections. If a patient is getting very frequent, very severe infections
08:12 – I have to kind of take that gulp and take a chance on doing that with long-term antibiotics knowing
08:17 – that that tilts the risk benefit more toward benefit. If she’s the kind of patient who
08:24 – comes in and every time she gets antibiotics it costs her six months of yeast infections and BV
08:30 – and vaginal alterations then I say no, let’s not change that anymore, let’s try to restore it.
08:38 – I’m not to the point of where the GI doctors are, of giving microbes in the gut to restore that but
08:43 – I would say that that’s a possibility we might be doing in the future in the bladder
08:47 – for people if we could find the right mix. You know what their normal microbiome was before
08:52 – say, measure it, treat them see how that’s altered and replace anything that might be a a beneficial organism.
08:58 – Melissa: How far away do you think we are from that kind of technology?
09:05 – Dr. Hlavinka: With next generation sequencing I wouldn’t be surprised if it’s not too far because there are already
09:10 – giving fecal transplants in GI these days and that’s as successful as anything for C. difficile
09:16 – and a lot of the irritable bowel and all of that. So we’re just behind that.
09:23 – That is going to be for even me, a very aggressive urologist with urinary tract infections,
09:29 – that’s going to be hard for me to accept is putting bacteria in the bladder that I always wanted to be sterile.
09:33 – Melissa: So you briefly mentioned yeast and BV. I was hoping you
09:37 – could explain the difference between AV and BV and how you go about testing for either?
09:44 – Dr. Hlavinka: So you’re talking atrophic vaginitis right, and bacterial vaginosis right? So atrophic
09:51 – vaginitis can – any kind of vaginitis, of course vaginitis is a generic term for inflammation of
09:57 – the vagina and it can come from many causes. It can actually be chemical if you have say,
10:04 – for instance if you’re putting metronidazole suppositories in the vagina and to treat
10:10 – BV, you can get a chemical vaginitis. I’ve seen that happen where the patient for all
10:17 – intents and purposes had a chemical burn in the vagina from the multiple metronidazole
10:23 – suppositories being put in there to treat the BV. And when we stopped them magically
10:29 – the vaginitis went away. But again, the ability to detect the right organism is so important
10:36 – and you cannot tell. I can have a 28 year old that’s been on the pill for 12 years
10:42 – and I can’t tell if it’s BV or atrophic vaginitis because she probably is estrogen deficient and
10:49 – the problem is that the PCR machines (and that’s called polymerase chain reaction).
10:54 – And let’s just take a minute to at least say the difference between PCR and next generation
11:00 – sequencing – they are different detection mechanisms and I’d like to wait until we get to the section
11:06 – on testing to go further into how PCR looks for a given set of organisms. It’s a preset test. In other
11:13 – words, if there’s 28 organisms in the urinary panel for instance, and you got organism number
11:19 – 29 or 30 it’s going to say negative, I don’t find anything all right. So that is part of the problem
11:26 – with BV and atrophic vaginitis and I keep trying to tell my gynecology colleagues, if you’re not
11:32 – doing NGS you don’t know what you’re missing and you’re treating these people incorrectly.
11:36 – And lo and behold, well I get them all. They come into my office and I’m seeing and I’m
11:40 – identifying them and making them happy. Because we are seeing a ton of resistant BV
11:45 – and we’re seeing a lot of atrophic vaginitis and younger women that need estrogen therapy.
11:51 – And maybe that’s all they need because younger women will respond more quickly to the estrogen
11:55 – therapy. So that I hope answers that question on how important it is to distinguish between the type of vaginitis – that it is.
12:03 – Melissa: Really important. And going back to again the yeast BV connection. A lot
12:08 – of people say they think that yeast infections or BV are actually causing the UTIs. Is it possible
12:15 – that this kind of imbalance is the reason that They’re experiencing urinary symptoms?
12:21 – Dr. Hlavinka: Absolutely. Any alteration in the vagina, like I said, putting that metronidazole
12:26 – suppository in there, treating with an antibiotic, treating the BV, treating the yeast infection – you
12:32 – are changing the very complex microenvironment of the vagina. And any alteration of that,
12:40 – you can change the vaginal pH one point and it absolutely completely changes the urinary
12:45 – microbiome. You can change the exudate, the vaginal exudate by chemical change you can
12:51 – irritate the vaginal wall causing edema or swelling of the vaginal epithelial cells,
12:56 – such that they become more fragile and susceptible to ulceration during intercourse and invasion
13:01 – by bacteria. So all of these things are very exquisitely intertwined in terms of maintaining
13:08 – proper vaginal health and prevention of any infection, be it urinary tract or vaginal.
13:14 – Melissa: You just mentioned sex as part of the potential issue here. Is it possible that during sex you can
13:19 – transfer organisms from the vagina to the urinary tract and that’s where the problem is coming from?
13:25 – Dr. Hlavinka: So when we are in our training we hear about a classic study done in the 50s
13:33 – that took a hundred women and they catheterized them before and after immediately after intercourse.
13:39 – 98 of them had bacteria in the bladder and again this was not a culture this
13:44 – was just a detection, but it was a highly centrifuged ultracentrifuge specimen. So they were
13:51 – looking. So almost every woman gets microorganisms in her bladder during intercourse it is just
13:59 – the mechanical aspect of inner vaginal intercourse. And that of course will happen with any sort of
14:04 – insertional devices. And I don’t want to get into oral sex versus vaginal penetrative
14:11 – sex but there still are microorganisms there too. But the bottom line is, that happens.
14:17 – So what happens? You’ve got a healthy system, not an aggressive organism, you void it out no problem.
14:22 – Well the issue is, is that intercourse can create more risk for infection because of
14:29 – that. So every woman gets them in there. So under the circumstances of the
14:35 – vaginal microbiome and risk for infection and urinary microbiome – absolutely you’re going to –
14:41 – whatever’s in the vagina is going to get in the bladder. And what we have to do make sure that it doesn’t
14:46 – set up shop. And that is the void before and after. The simple things like that. Avoid positions that
14:52 – may be causing you problems. You know perhaps if some people need to shower, and I believe
14:58 – are we going to get into the issue of passing an infection between partners in the next section?
15:04 – Melissa: Definitely, in a different section yes.
15:06 – Dr. Hlavinka: So that certainly is something to identify. And most of the time showering does help – that won’t
15:13 – eradicate it but most of the time showering before intercourse if that you’re susceptible.
15:17 – Melissa: And do condoms help at all with the transference?
15:21 – Dr. Hlavinka: So, unfortunately it is a mechanical aspect of intercourse
15:27 – that causes this vaginal microbiome to get into the bladder. Now if a man has an infection say for
15:34 – instance he has a prostatitis or chronic urinary tract infection the condom might help prevent
15:39 – that and again we can explain that more in the section about couples passing infections back and forth.
15:45 – Melissa: Okay, sure. So while we’re still talking about the urinary microbiome I wanted to ask a few questions
15:49 – about biofilms as we received some from our audience. The first is, what is your understanding of the involvement of biofilms in recurrent UTI?
15:58 – Dr. Hlavinka: We really didn’t understand that environment at all
16:02 – and in urology we thought that microbiomes were other specialties’ problems, like
16:12 – orthopedics, wound care, people who did implants. Those of us that did urinary tract implants
16:19 – knew about microbiomes and biofilms. But the bottom line is that we didn’t really think that
16:24 – that applied to the bladder. Now maybe in people with kidney damage who had sort of
16:32 – stagnant areas in the kidney and they sloughed these parts of the kidney and there was kind
16:37 – of a chronic kidney infection, yes we thought that would be the case but we couldn’t identify them.
16:42 – All we could do is get a urine that they voided out and sent that for a culture, and we missed so
16:47 – much. So the capacity to detect an infection, its location, is undergoing revolution not just in
16:55 – urology but across the spectrum of organ systems. So for instance I just heard about a
17:02 – doc, a urologist in Loyola of Chicago who is studying actual different parts of the prostate
17:09 – and the different microbiome in different parts of the prostate. I have no doubt that that will happen
17:14 – with the bladder also. The bottom line is that I’ve long suspected the persistence of a
17:24 – biofilm in the urinary tract as the cause of a persistent infection. And the reason is that we
17:31 – used to see this thing we call trigonitis. Trigonitis was this area of the bladder where the
17:35 – ureters come in just inside the bladder from the urethra and it was sort of this filmy layer,
17:41 – whitish layer. Well we thought that was just a plaque in menopausal women that was due to lack of estrogen.
17:46 – Well, that was because we’re dumb old male urologists and really didn’t care because we were going to
17:51 – burn it or biopsy it or something by gosh, or do a urethral dilation, we’ll see you later honey.
17:57 – And that always bothered me. Also I used to see what we called cystitis cystica.
18:02 – Basically it’s acne of the bladder. You’ll see these little tiny pimples in the bladder and
18:07 – they’re pustules. Okay what does pustule mean? Well pustule means full of pus
18:12 – and pus is an inflammatory liquid. So just like if you pop a pimple, well that’s got bacteria,
18:18 – it’s got propionibacteria and acnes and all that other stuff. There’s infection and white cells and all
18:24 – that other stuff. Well, that I’m convinced is in the bladder. I also saw patients who had no IC symptoms
18:31 – have these florid ulcerations and cysts and and plaques formed throughout the bladder and you
18:39 – know, should I have biopsied them back then and taken a piece of it to look for microbes? I should have but
18:44 – then we didn’t have any means of detecting them so that would have been overly invasive. Now i’m
18:48 – doing a lot more of that. I’m going in and sampling these areas. I’m sampling the normal bladder. I’m
18:54 – sampling these ulcers, these plaques. We’re finding that these are full of bacteria. They’re full of
19:00 – inflammatory response and no doubt that they are a component of the persistent infection conundrum that we’re facing.
19:09 – Melissa: That’s very interesting because you do often hear that one of
19:12 – the signs of IC is these Huhner’s lesions and that that is an indication you have IC and therefore
19:18 – have to manage this disease forever, though I have spoken to other clinicians who say it’s a sign of
19:23 – infection potentially and that it may be able to be treated. So if you see these lesions, you
19:29 – do a biopsy, find microbes, do you then initiate treatment as you would for another kind of UTI?
19:36 – Dr. Hlavinka: Well to start off I’m glad we’re going into that right now because it segways into
19:40 – discussing this and as a parenthesis please ask those providers to contact me.
19:47 – I’ve done three IC patients now with their Huhner’s ulcers and I resect them.
19:53 – Now, you’re supposed to resect the Huhner’s ulcers but I thought that didn’t make sense, it’s just going to
19:56 – cut out an infection or you know cut out a scar or an ulcer but that is effective cut them out,
20:02 – but what I did was, in these three patients, and the patients agreed to it – again this is
20:06 – no clinical trial, they don’t have an institutional review board – but they were miserable. And once
20:13 – I got next generation sequencing I felt that there was a capacity to give them an answer. So
20:18 – before resecting them I biopsied them and I found a biofilm with multiple organisms. I treated them.
20:24 – In two of them it went away and the third one it did not and I had to resect it, but she’s better
20:30 – after that and we found that there was a different organism in an area that I hadn’t biopsied. So
20:35 – I’m going to resect all of them now and send them because I feel like that’s going to leave
20:40 – potential infection behind. It’s a short early series but this is my process now and I discuss
20:45 – this with the patients and I believe that more and more IC experts should be getting on board for
20:52 – this. Again, they don’t know how to identify the biofilm and only by sending the entire ulcer
20:58 – to next generation sequencing are we going to be able to identify things we might be missing.
21:08 – Melissa: Can you just explain what resect means for people that don’t understand?
21:13 – Dr. Hlavinka: Resect means to remove by surgery and typically when you do that with a scope you have these
21:14 – instruments that basically, well, they’re kind of like they’re kind of like gougers. They just
21:20 – go in and sort of gouge something out like you’d scoop out
21:24 – of a melon, you know scoop a little scoop out of a melon – miniature versions of that.
21:30 – I hate to be crude but believe me, if you got it done by me I’d explain a lot more in detail
21:35 – and get you through it. And really, they’re small, they’re small devices and they’re small
21:41 – ulcers so we’re talking about no more than about the skin of your pinky knuckle. That’s about the biggest piece of tissue you’d resect.
21:50 – Melissa: Is it a painful procedure for the patient?
21:55 – Dr. Hlavinka: Pain is subjective from a standpoint of the patient and the provider so I’m someone
22:05 – who’s exquisitely sensitive to pain because I’ve treated chronic pain patients my entire career
22:11 – and I realized how horrible we medical providers have been to people with chronic pain. I apologize
22:17 – for all the horrible stories I’ve heard. My very best friend has had chronic pain after
22:24 – cancer chemotherapy and has lived with it his entire life so I know the truth.
22:31 – And I know that all the opioid addiction is once again a very sad way for docs to pass the
22:39 – buck. What I do is I do something beforehand. I inject the ulcer with a needle called
22:47 – a Williams needle, through a scope with a local anesthetic in the area. So it’s like if you had
22:53 – to have something in the dermatologist and they would numb underneath it and then resect it and
22:58 – then sew it up. I’d do that first, so that sort of helps the pain because before the resection
23:03 – and then I put a solution in the bladder with the long-term antibiotic. I should say a
23:08 – long-term analgesic and numbing medicine and a bladder anti-irritant and I
23:17 – leave that in for an hour while the patient’s waking up from recovery. Then I take it out
23:22 – and that that helps. That helps but I’m not saying it makes it pain-free. But by and by I believe pain
23:30 – can be decreased. Also I use B&O suppositories Belladonna and Opium suppositories, an ancient
23:36 – urologist trick that decreased spasm. I get one of those before they wake up in the recovery room
23:42 – and you do all sorts of things to diminish it but I think it depends on the patient’s pain scale. If
23:47 – a patient has a high pain scale they’re probably going to have significant pain with this resection.
23:52 – Melissa: Okay that’s good to know. So there are two directions that I want to go in. One is further down the IC
23:58 – treatment path, but I also want to ask a couple more questions about biofilms.
24:02 – You’ve mentioned NGS as a way to actually do testing to maybe pick up multiple organisms.
24:07 – Is seeing multiple organisms on test results a potential indicator that a biofilm is present?
24:14 – Dr. Hlavinka: Absolutely yes. If you have multiple organisms and NGS tells us that, then my opinion is that’s a strong indicator of a biofilm.
24:23 – Melissa: From a patient perspective again, when they’re trying to
24:24 – identify whether biofilm may be involved, if taking antibiotics brings relief but the symptoms always
24:30 – return when the antibiotics are ceased, could that also be an indication that there’s some kind of biofilm involved in the bladder?
24:37 – Dr. Hlavinka: Yes. The reason is, is that failure to eradicate
24:42 – an infection despite appropriate antibiotics, and again appropriate antibiotics is indicative of a
24:48 – complicating factor and that can be something as significant as a foreign body – a stone, an ulcer –
24:57 – and in my opinion a brand new topic of biofilm. And honestly, Melissa, I feel like
25:05 – we haven’t even begun to touch the surface. For instance in males and prostatitis I’m convinced
25:12 – that there are multiple micro-biofilms in the body, I should say in the prostate. The prostate is like
25:18 – like a lung with a little alveoli, little lung pockets that we breathe through.
25:23 – All the little tiny glands in the prostate that produce semen, in my opinion there’s probably
25:31 – dozens of different micro-biofilms in those that could be explaining,
25:35 – and maybe one is stronger, you know, one is predominant today and next month another
25:39 – one’s predominant. So you could repeat it and them be different. And I’m convinced that
25:43 – say for instance if I look in a lady and she’s got 20 of these little pustules in there, these
25:49 – little pimples in the bladder, who’s to say that there’s not 20 different biofilms micro-biofilms
25:54 – and each one of them might be different. Now from a practical standpoint you’re not going to
25:58 – biopsy all of them because that’s just too much trauma to get the answer, but you might
26:03 – start learning to biopsy three to four to five and that’s what i’m going to do in the future.