00:00 – Dr. Hlavinka: We have a large component of Interstitial Cystitis that are undiagnosed or under-diagnosed infection.
00:20 – Melissa: So I wanted to ask you a couple of questions about recurrent UTI and IC treatment and how you
00:25 – work with your patients. The first question is, do you have any general advice for people whose
00:30 – symptoms disappear when they take antibiotics and then return again a short time later?
00:36 – Dr. Hlavinka: IC is changing, the field around IC is changing. I believe the thought leaders in Interstitial
00:42 – Cystitis and urology and urogynecology and women’s health have taken on the notion that we
00:52 – have a large component of Interstitial Cystitis which is undiagnosed or under-diagnosed infection.
00:59 – In my own practice that was one of the first subset of patients that I discovered
01:05 – the benefits of next generation sequencing technology, because the patients acted as if
01:11 – they had an infection on top of their Interstitial Cystitis. They complained of worsening symptoms
01:17 – when they had a urinary tract infection and knew exactly what those symptoms were like but then
01:23 – the failure of the traditional cultures to be able to deliver results that we could use to treat
01:29 – successfully was a big part of that. So, those were among the most helpful and I think
01:38 – at least a half a dozen of them at the very beginning which sold me quickly on next
01:42 – generation sequencing particularly in patients for whom infection symptoms on top of another entity
01:50 – could be problematic. So, I would say, and I’m getting stronger by the day from the standpoint
01:58 – of my emphasis on this, and that is, if you have an infection or history of infections
02:07 – and you think you have an infection or if you have a chronic condition which is exacerbated by
02:12 – an infection on top of it, complicating it, then I would demand your doctor learn how to
02:18 – do next generation sequencing and run that test. Because you will find, in my case,
02:25 – probably 80-90% of the patients, indeed I was interviewed last week by a lab asking for clinical
02:35 – relevance and I told them that we really have to rethink what we call an infection these days,
02:51 – and limitations in technology are the most important thing. You mentioned people that
02:58 – have been diagnosed with IC that have an infection on top of their IC, which is the language that we
03:02 – hear a lot. If they have been culturing negative and then sometimes they culture positive,
03:07 – which is when they say they have the infection, do you think the whole set of their symptoms could
03:12 – actually be caused by infection, or that they do have a UTI on top of whatever else is happening?
03:18 – I think the simplest thing to do is to identify and treat, and if you identify
03:23 – with next generation sequencing you’ve done everything you can. Now some of those are
03:29 – frustrating in that even then the NGS is negative. However, I just took a lady to the operating room
03:37 – last week and we were going to do biopsies of her lesions because we’d talked about that,
03:44 – and it turned out that she actually had an ulcer and the ulcer was positive and we sent that for
03:48 – tissue analysis and that showed the infection. So I’m convinced that IC is probably either bacteria
03:57 – or bacterial product buried under the surface much like acne is or much like cellulitis is where you
04:04 – really don’t have the infection on the surface. There’s not an abscess or a pustule or something
04:12 – like that, that’s a medical term, but you know, a big round pocket of infection like a pimple.
04:17 – A pustule is a pimple, the classic white head. So you see these in the bladder on endoscopy and you
04:26 – say well that’s got to be something, that’s got to be infection, so my goal is to biopsy
04:31 – as many as I can. Now, good news, bad news – the bad news is I’m not finding them, and the good
04:38 – news is that because I’m doing the MicroGenDX ahead of time, finding them and treating them,
04:41 – the findings on endoscopy are less pronounced. I’m still seeing the occasional pimply bladder
04:47 – as I call it and I’m going to start biopsying those and sending them. And dollars to dimes,
04:52 – or pounds to pence, is that what you say there? Pounds to pence, it’s going to be an infection.
05:02 – Melissa: And if you do find infection in an IC patient, is the treatment the same as that which you
05:08 – would use for a recurrent UTI patient?
05:12 – Dr. Hlavinka: So I had a brilliant urogynecologist talk about
05:20 – female pelvic floor issues. And the notion of physiologic pelvic floor dysfunction, like from
05:30 – prolapse or hypertonicity, was one corner of the diamond. The other was pure IC. The other was
05:40 – pure infection and the other was pure overactive bladder, neurological bladder. So you form this
05:49 – diamond, can you see that? And at the corners were these, and his point was that every woman
05:56 – is somewhere in there, who’s had these conditions before. They’re not pure pelvic floor, pure IC.
06:02 – So if you think of this as sort of a constellation of entities that contributes one versus the other
06:13 – and sure the pelvic floor may manifest if you’re had ten infections in a row and you’re IC is
06:18 – flaring and your overactive bladder, and you’ve had a rough week with diet or something. So I
06:24 – tend to think of it this way. So every time I see a woman who is flaring, whatever her diagnosis,
06:29 – that means even she comes in as pure overactive bladder, I do the same thing – could this be the
06:35 – other three? And so, by not treating all four of those at once, you’re really not getting the
06:40 – patient to improve as fast as you possibly can. And when I said that it means I’ve probably got
06:46 – to do that. She’s probably going to get a boost in her overactive bladder medication, maybe
06:51 – Interstitial Cystitis therapy enhancement, maybe a referral back to a physical therapist
06:56 – or whatever helped her in the past, so that’s how I would approach that. It would be great
07:00 – to say that they all got better just with antibiotics, but I can’t say that. What’s
07:05 – your opinion on long term, full-dose antibiotics, like the protocol that is often used in the UK?
07:12 – I am changing, I was a big fan of suppressive antibiotics in the past.
07:19 – Many times that was all we had. The problem is, if you’re dealing with
07:25 – inadequate information or misinformation or negative cultures or inaccurate cultures
07:29 – and you put somebody on long term antibiotics, you’re basically calling this a therapeutic end
07:37 – point and you’re saying I’m going to be satisfied with clinical outcomes. And obviously that’s
07:45 – ok, if it’s ok. And that’s not glib. The bottom line is that many times doctors say ‘you’re ok’,
07:55 – I’ve got you on the right antibiotic, the culture says you’re on the right antibiotic, 90 days, see
08:00 – you… And you’re not good, you’re not happy and you’re coming and telling me that your symptoms
08:06 – are worse, so my experience with the refractory recurrent urinary tract infection patients is that
08:14 – they weren’t doing well, and either I gave up because I didn’t have anything else to offer or
08:20 – I had to ask them to live with their symptoms. And we kept jumping ahead, staying one ahead
08:24 – with the next antibiotic. And I would say that’s ok, as long as you use the latest technology to
08:30 – identify what organisms are there. Next generation sequencing is better at identifying, but it
08:38 – doesn’t do anything bacterial resistance because micro-organisms are smart
08:42 – and they don’t like being found out. They like to get away with therapeutic madness.
08:49 – So my opinion is that it would be ideal to use a combination of prevention, a combination of
08:57 – shorter interventions, a combination of antimicrobials that aren’t antibiotics
09:04 – and sort of an overall program of health that is better than that. Now, if you get to the point
09:11 – where you’ve tried all that and there’s nothing else but a daily, single antibiotic, sure, I still do that.
09:17 – Melissa: What about bladder instillations, do you ever recommend those for your patients? Antibiotic bladder instillations that is.
09:23 – Dr. Hlavinka? In most of the ones that I’ve had to do are patients with
09:32 – complicated urinary tract infections from either neurologically mediated issues, retention due to
09:39 – spinal cord injury, multiple sclerosis, stroke, things like that, or they have chronic indwelling
09:44 – catheters or something – some complicated urinary tract history where I really don’t have any
09:49 – choice. I haven’t had that many patients benefit from bladder instillations and the invasiveness
09:54 – of it, in order to put a catheter in, once or twice a week, and instil the bladder. Typically
10:01 – I will add antibiotics in a patient with an IC flare, I’ve found that helps. I also add
10:10 – antibiotics to my botox injections for the patients with overactive bladder because I feel
10:15 – the particular aminoglycoside antibiotic, I think it helps prolong the benefit of the botox. But the
10:23 – instillations in patients that can feel and have to catheterize themselves, they’re uncomfortable
10:29 – and are also a chance for infection if not done correctly.
10:36 – Melissa: What about bladder fulguration, do you ever use that technique and can you briefly explain what it is?
10:43 – Dr. Hlavinka: Do I look that old, Melissa? I mean, just kidding. So the older urologists, and there may be a place
10:50 – for that. There are – everything that’s old is new again – and the newer fulguration of the pseudo
10:59 – membranous cystitis and the acne of the bladder that I called earlier the ‘cystitis cystica’,
11:07 – the fulguration of that, I can see that that can be beneficial. I don’t do it. Again I feel like
11:15 – the tools are just not there to define that. We just don’t really know what that is
11:19 – and scarring can happen at any time. It can happen the first time. I’ve had a patient get a
11:26 – urethral stricture, a female which is rare, get a urethral stricture from a single catheterization
11:31 – during an epidural, during her delivery. And so the bladder mucosa, the bladder lining is a very
11:38 – delicate thing, especially in someone who has had recurrent infections, or IC and all these
11:42 – other irritative issues. Why nuclear them with thermal energy or laser energy? I don’t see it.
11:53 – Melissa: So, what is your general approach to diagnosing and treating recurrent UTI?
11:58 – Dr. Hlavinka: Again, when you have a referral practice like mine, you already have gotten 5-15 negative
12:06 – cultures or useless cultures, or cultures that showed something, but it was not the right thing
12:10 – to treat, so why waste my time with something like that? Sure, in the rare case where I get
12:17 – a next generation sequencing naive patient, yeah I’ll probably go through some traditional cultures
12:25 – or a PCR (polymerase chain reaction) is sort of in between traditional cultures and next generation
12:31 – sequencing. But that’s just so rare these days that it’s probably one in a hundred patients. I go
12:39 – straight to next generation sequencing, I look at the organisms that are shown in the distribution.
12:50 – I’m very specific about how the specimen is delivered because if they’ve just finished
12:54 – antibiotics or are still on antibiotics it’s useless. In fact four days is probably
12:59 – about the minimum to be able to get any meaningful information. And then once I see the organisms
13:04 – I decide which way to treat, and I try to do, because this is new information most of the time,
13:09 – and by the way, the question was asked during a presentation last week – how many are negative
13:15 – at the outset? How many are negative or not helpful, with a contaminant or something.
13:22 – And that now number in our now database of over 800, is 8%. Of those, if I kind of threw out the
13:32 – ones that were too soon, I bet the number is even lower. So that’s a big number of
13:39 – goodness in your initial diagnosis. Now does that mean I took 92% of patients with recurrent UTIs,
13:45 – I did their first next generation sequencing and I cured them in ten days of antibiotics? Well,
13:49 – no, because again this is a really tough disease with all sorts of multiple contributing factors
13:56 – and so under those circumstances that’s what I start with. I treat it.
13:59 – I try to do a shorter course because I just want to see what treating the correct organism does
14:04 – and then we observe. Again, the whole notion of what is an eradication of an infection these
14:09 – days is changing because a negative culture means nothing to me. And I can’t tell you that getting
14:14 – rid of the organism on the next generation sequencing is the goal either because often
14:18 – that’s elusive. You can get a decrease in the reads, which is just sort of the copies of the
14:25 – DNA the machine reads. So I use decrease in reads. If I don’t get any decrease in reads,
14:32 – even if it was sensitive by the recommendations of the panel, I think that’s a failure. If a patient
14:41 – had no symptoms and I didn’t decrease the reads at all on the next generation sequencing, would I
14:47 – consider myself a success? No, that’s not enough. I think that the next generation sequencing is so
14:52 – precise that it’s really not appropriate to say that we’ve done anything without that. So that’s
14:58 – kind of how I do it and then we just observe and we repeat and we treat and we try these other
15:04 – things that we’ve talked about with prevention in between, once we know we’ve gotten rid of what
15:08 – was there. And then if we have to we keep them on longer courses of antibiotic.
15:15 – Melissa: And what’s thedifference between that kind of treatment and how you would approach chronic prostatitis in a male?
15:20 – Dr. Hlavinka: Again, as my therapy evolved, I saw men for this refractory prostatitis, and I have a
15:29 – big referral practice for this, and I just want to re-emphasize that often chronic prostatitis is an
15:39 – infection that is passed between couples, between members of a couple, because
15:44 – in prostatitis what lives in the semen is representative and that’s the specimen I get.
15:49 – In the beginning I started out getting urine specimens from the guys and that was helpful
15:54 – but not that helpful. And then I started doing this so-called prostate massage which they hate,
16:00 – but you know, men need some torture just like women every time they go to see doctors, just
16:05 – kidding. But guys are, you know, they’re pretty much weenies and they don’t really put up with
16:10 – that. The bottom line is, the prostate massage and then having the patient void in a cup afterwards
16:16 – was my next step because that’s what all the books say to do. I know there are particular
16:20 – urologists that think that’s the way to go. I have not found that helpful at all. A semen specimen,
16:26 – if the patient can produce semen, because that comes from the prostate and the seminal vesicle,
16:31 – that’s where the infection lies. So getting that specimen and sending it is absolutely
16:37 – essential as far as I’m concerned, in making that diagnosis. And the same thing with men, is that
16:44 – you’ve got to treat first and see, because most of the time, and this has never been discovered – so
16:49 – I’m getting a brand new organism that’s never been treated – many times with an antibiotic,
16:54 – sometimes a combination of antibiotics for more than one organism and then we see what happens.
16:58 – Now the prostate has poor antibiotic penetration so it’s difficult to eradicate infection, so
17:05 – it’s important to treat for longer courses than you would, say, for a female UTI.
17:09 – Quite honestly there’s no such thing as a simple UTI in a male.
17:12 – They tend to be almost all complicated when they come to see me. So that’s my practice
17:18 – with that. And my success has been good. I would say people are coming to see me for that reason.
17:25 – We even are doing something quite exciting. We’re doing what’s known as intraprostatic injections of
17:31 – antibiotics for those that are very refractory and we’ve had some good success. We now have used a
17:39 – trans-perineal approach, meaning we don’t have to go through the rectum, through the rear end, which
17:44 – really cuts down risk. This trans-perineal approach with ultrasound guidance and
17:50 – injecting in the prostate is very exciting because I believe a lot of these patients just couldn’t
17:55 – be helped. I have anecdote after anecdote of male patients that just were miserable, couldn’t work,
18:01 – couldn’t function quite honestly. And everybody called them the male version of chronic pelvic
18:06 – pain and no, that wasn’t it. We actually here from quite a few people in that situation which
18:13 – is why this question has come up and it does seem a difficult thing to treat. Yes it is.
18:20 – Melissa: You said you’ve had some good success with that. Do people with recurrent UTI
18:24 – actually recover? Do you have patients that have recovered from this and are well now?
18:30 – Dr. Hlavinka: I’ve been doing next generation sequencing three and a half years and I will tell you that the detection
18:40 – is excellent. There is far superior detection of infections at a much more accurate rate than
18:48 – anytime ever before in my career. Am I eradicating infection lifelong because of that new technology?
18:56 – Honestly, Melissa, I don’t know yet. There are those for whom I need to go back and look
19:03 – at my success rate and document that. That is something I really haven’t done.
19:11 – We’re so thrilled to have this new tool for detection, it’s hard to say ok,
19:17 – let’s not throw out the baby with the bathwater and criticize results when we never had anything
19:21 – like this before. I know it’s better. I know there are people for whom the impact on their health and
19:27 – the quality of life is improved. They come into my office every day and hug me (before COVID),
19:34 – and I’ve got anecdote after anecdote as I said, of patients for whom this is a life save,
19:39 – a game changer and a quality of life saver. And for that reason, I would say that yes, there is a
19:46 – chance for a cure. There is a chance for certainly diminishment in impact on quality of life.
19:52 – Melissa: We have another question from a couple of members of our audience which is, could a foreign object
19:58 – in the body, such as a breast implant or vaginal mesh, actually be contributing to recurrent UTIs?
20:07 – Dr. Hlavinka: This is a frequent question and the answer is dependent upon the type of foreign body and
20:16 – where it is, and has there been any incidence in infection before of that implanted material.
20:26 – The issue with say, for instance, an eroded vaginal mesh, that’s
20:32 – unequivocal, yes that could contribute, that’s a simple answer to that one.
20:38 – The answer to a foreign body such as, say for instance, in
20:46 – an auto accident, and a piece of metal or something like that, and there’s a foreign body
20:50 – that may be impacting the mechanics of an organ, then yes, absolutely, that’s another easy one.
20:57 – But when you get to things like breast implants, vaginal mesh implants that are functioning well,
21:07 – it’s a little bit more tricky to say that there’s cause and effect. We know that there’s an immune
21:13 – system boost to the foreign implant, even in one’s that have not caused the patient any problems
21:21 – whatsoever – you’ve had it in for years, you don’t even know it’s there – and you remove them and you
21:27 – see this sort of inflammatory rind around them, inflammatory peel around it that the body has
21:32 – walled off. If you send that to the pathologist, the results are some inflammatory cells,
21:37 – white cells in reaction. I do neuro-simulator implants, and I’ve removed these and I’ve seen
21:43 – that, I’ve seen the tissue as it comes out. So I think that it’s probably a combination
21:50 – of local factors that create a pro-inflammatory response that weakens the immune system. And the
21:57 – breast implant surgeons would tell you that that’s not the case, they feel like they’re sort of the
22:04 – pariahs now in the surgical field. The bottom line is that we’ve had enough patients with
22:12 – these histories of, I’ve had this condition, it was really bad, or it was worse,
22:19 – got my foreign body removed and my condition is better. So to me, that is that sort of anecdotal
22:26 – evidence all of us docs in the era of COVID have learned to pay attention to. To trust our own
22:31 – instincts about a patient and finally listening to people who say my infections are fewer since it was out – there was a reason for that.
22:38 – Melissa: If people would like to make an appointment to see you are you actually taking on new patients at the moment?
22:45 – Dr. Hlavinka: Yes I am. Yes I am.
22:47 – Melissa: And for people who can’t see you, do you have advice for people about how to speak to their own doctor about this problem, and how they can move forward?
22:55 – Perhaps we should include some of the excerpts from this discussion about my experience with the next generation sequencing, my protocols. That’s not to say
23:04 – mine is the right way, I’m very specific in how my practice evolved. My practice is
23:09 – a fairly unusual urology practice with all these different types of patient populations that have
23:16 – merged to make next generation sequencing quite important to me – essential. But on
23:22 – the other hand I’ve got a lot of experience and would be glad to share it with their providers.