00:00 – Dr. Hlavinka: But again, in a symptomatic patient when I’ve got the choice between traditional cultures, which I
00:05 – know are going to be a fail, and NGS, I’m going to pick the one that’s going to give me more accurate information
00:24 – Melissa: Let’s talk a little bit more about testing. Can you first explain to us why standard
00:28 – urine culture is inadequate, especially for recurrent UTI?
00:37 – Dr. Hlavinka: Can I, boy can I. Yes I can. I got introduced to next generation sequencing DNA testing three and a half years ago
00:46 – when I was particularly frustrated with a group of my complicated UTI patients and not being able to
00:52 – find answers. I had had the lab throw out a total of seven cultures on a single patient despite the
01:00 – fact that I even called up the head pathologist and asked for special handling of it, to get me
01:06 – an answer. And they just they simply can’t do it. Everything is automated, there’s just no way
01:12 – to change the limitations of traditional cultures. So let’s go back to high school
01:17 – biology when you first dealt with the petri dish. And you had the little petri dish and had
01:21 – a little agar plate on it, which is food for the bacteria, and you coughed in your hand and you took
01:27 – your swab, your cotton swab and you swabbed it on the little agar plate. You waited two days and
01:33 – you watched it grow and said, oh that’s great, look at that! Look, there’s bacteria growing and there’s
01:36 – different kinds. And you have little colonies, little dots grow up. Little white or pink dots
01:40 – grow up. And then they gave you something called penicillin and it looked like a little, you know
01:46 – tab you put on to stop your bleeding, or your you know, something like that little paper tab.
01:50 – And you put that on there and it’s penicillin, and then two days later you saw the bacteria
01:54 – get killed by it. And that’s that is how Robert Koch in Germany in 1848 invented cultures. And
02:01 – there has literally been no significant change in the technology, other than to automate it,
02:09 – since then. And the automation has made it worse, as I said earlier, because it simply makes it where
02:14 – human beings don’t intervene. So the capacity to identify multiple organisms to sub species,
02:21 – to create different time frames for looking at the plates and finding out what’s growing, that
02:27 – just doesn’t exist anymore. And so you’re left with what the lab gives you. And you could be charged
02:32 – anywhere from in the United States 48 dollars for a negative culture, to 140 that has multiple
02:39 – organisms that need to be sub-speciated. And when you look at next generation sequencing costs it’s
02:45 – not cheap compared to that but it definitely gives you more information. So that is what the
02:51 – standard urine culture does. And it must be done within two hours, it must be sent within two hours or else.
02:58 – Melissa: Which must never happen.
03:01 – Dr. Hlavinka: Right, exactly. You typically have to do a special technique to prep yourself, where you have skin contaminants that make them throw it out.
03:11 – And if you use too much of the little soaps it can kill bacteria so it’s very difficult to get
03:16 – it right. It also has a limitation into the time frame that you can get results back. Again, now
03:24 – next generation sequencing is getting back pretty quickly such that that’s no longer an issue. And
03:30 – in some places, in the urinary tract infections realm, up to 70% (of cultures) were in error.
03:37 – Maybe even higher numbers were in error, meaning they didn’t find an organism that was there, or
03:42 – they found organisms that weren’t there, that they found, that really weren’t pathogens
03:48 – and were contaminants. Now that is a problem with next generation sequencing too, it is not with PCR,
03:54 – but PCR has the fault of not being able to find something it’s not looking for. Let’s look
03:58 – at polymerase chain reaction or PCR. So PCR is, it’s called polymerase chain reaction and what that’s
04:07 – looking for is amplification of a genetic signal. You can either use RNA, like they’re doing for
04:14 – the Coronavirus or you can use DNA like we do for most microbes. And you take a little piece of the
04:20 – DNA – a piece of the genetic code – and you have a machine that amplifies it big time and fast,
04:26 – so you can get a read on it. You’re going to get an identification and you can get an estimation of
04:32 – the number of microorganisms by the amount of genetic material that’s there. So you can
04:37 – identify it and predict how much is there by that, and that’s what PCR can do, But PCR is a probe,
04:46 – meaning it only looks, I should say, it only finds what it looks for. And if that sounds glib
04:51 – it’s not, because let’s use the analogy of a lego detector right. Let’s say you’ve got a box with,
04:58 – you know, 28000 legos in it. All right. Each of them individual. And you know that your lego is a cube
05:06 – with three prongs, right, that’s two centimeters by two centimeters. So what PCR does is it goes
05:13 – in there and it looks for that exact lego. If it doesn’t find that exact lego, if it’s two by three,
05:19 – it says ‘nothing there guys, nothing to be worried about’, pull out and no lego searching anymore.
05:25 – What next generation sequencing does is it goes in and it says ‘ah oh there’s a peg, okay okay,
05:32 – there’s a side that’s two centimeters, oh there’s another side, there’s a third side okay, it’s a cube.
05:38 – Oh there’s a second peg, there’s a third peg, bingo! E. coli’. And it pulls out the two by two by two
05:44 – three prong lego. And so that is why NGS is so unique and so valuable. It’s just going to find
05:51 – that that two by two by two three prong lego 99.4 percent of the time accurately, all right.
06:00 – And that’s so important to recognize. Now maybe that particular lego isn’t causing your infection,
06:06 – but at least you know it’s there and that’s what I think is the most important. And if you’ve
06:11 – got that lego in there, and you know, you’ve got nine million of them, well then you know that you’ve
06:18 – got a problem, all right. And that’s the other thing, so NGS can also give you an estimation
06:23 – of the bacterial load, the microbial load, like PCR can but it’s much more accurate at identifying
06:30 – precisely the organisms that are there.
06:33 – Melissa: So when it comes to treatment using this kind of technology, is it the bacterial load that really tells you whether
06:38 – something should be treated, or is it the fact that it’s a known pathogen?
06:44 – Dr. Hlavinka: That is a very, very good question and just, oh my gosh, there are people that people that want to pay me to give them that answer.
06:54 – And the answer to that is, after doing this for three and a half years with over 800 specimens,
07:00 – the answer is yes. And I’m not again being glib, but the answer is that a known pathogen
07:08 – in a symptomatic patient with a low bacterial load – I’m going to be cautious and I’m going to treat. And
07:16 – I’m going to do that because if they’re having symptoms, if they’re having symptoms now, you know
07:21 – a little bit of urinary frequency, and it’s a two percent read of E. coli maybe not, but if burning,
07:28 – frequency every 15 minutes, low grade fever, feel terrible, yes I’m going to treat that, because I may
07:33 – have an infection that I failed to treat adequately. On the other hand, if you have a really high load
07:40 – of something that’s a known contaminant or a known commensal organism – commensal means
07:47 – an organism that normally lives on the body in an unpathogenic way, in a non-infectious way – then
07:53 – I might ignore that, but if they’re symptomatic and that’s the only thing that the NGS gave me,
07:59 – I will treat that too. And so you can see that – I’ve seen that with Gardnerella in
08:04 – the bladder in women, with Lactobacillus in the bladder, with women where nothing else is there.
08:09 – It’s not a contaminant. There’s a high read, high load and I treat them and they get better.
08:16 – Melissa: That’s interesting. And one question that we get a lot – I’m not sure if you can answer it – but how do
08:20 – you know that the DNA found using this technology is alive, or represented something that was alive?
08:27 – Dr. Hlavinka: You don’t. You don’t. And again, I deal with symptoms. And the fact is, is that
08:32 – I know that this technology is superior, so the bottom line is that there are there are downsides
08:39 – of NGS and that could be one of them. But again, in a symptomatic patient when I’ve got the choice
08:45 – between traditional cultures which I know are going to be a fail, and NGS which may give me some
08:50 – false information based on non-viable nucleic acid, I’m going to pick the one that’s going to give me more accurate information.
08:57 – Melissa: So we do see that it’s not exactly standard for clinicians to use
09:03 – this kind of technology for bladder infection, and someone sent in a question that’s very relevant
09:07 – for 2020, which is why are clinicians so willing to use this technology for something like COVID-19,
09:13 – but they are not willing to use it for infection in the bladder?
09:17 – Dr. Hlavinka: That’s a very good question and if I had the answer, I would have the answer to why clinicians do what they do on a daily basis.
09:25 – I give the example of a stethoscope. Stethoscope is basically the same it’s been for 150 years,
09:32 – just like urine cultures and we haven’t really made that many improvements in it. What if somebody
09:39 – invented a chip that you put in a stethoscope that made your diagnostic listening to the heart sounds
09:47 – and lung sounds just 98.97% more accurate and you can’t screw it up. You know you’re going to get,
09:55 – and it’ll give you a readout and show you, oh my gosh, you have that S2 sound in the heart, or
10:01 – you’ve got a gallop sound, or you’ve got a murmur and you missed a murmur. What would happen to
10:06 – stethoscope sales, all right? Old ones would go away, no one would buy them, they would be historically in
10:13 – museums and there’d be a run on stores to get the newest type of stethoscope. So I don’t understand
10:19 – why my colleagues will not incorporate this. It’s not that hard. It took three months of doing dual
10:26 – cultures and next generation sequencing. When I started this, Melissa, I didn’t know anything
10:30 – about PCR even. So I kind of got PCR and NGS at the same time, which was good for me because then I
10:37 – saw the limitations and benefits of both. But I can certainly tell you that the limitations
10:42 – of traditional cultures are vast and leaving behind traditional cultures for newer technologies
10:50 – is absolutely essential. It is not just state-of-the-art, it’s standard of care, and providers that don’t
10:57 – incorporate this into their practice are not practicing state-of-the-art medicine. And I will
11:01 – say that to their face. You can pass this on to them if they need more education about it and
11:07 – its benefits. Send them my email, give them my cell phone. I’ll be glad to talk to them.
11:13 – Melissa: I may do that. We actually receive a lot of emails from people who have been diagnosed with Interstitial Cystitis
11:18 – based on negative urine culture even though they have symptoms that are very similar to UTI.
11:23 – In that case would you say that those people may benefit from pursuing testing with different technology?
11:29 – Dr. Hlavinka: Absolutel. I’m glad you got into that subject because once again we
11:35 – are looking at a new technology. And maybe that news type of stethoscope tells us about sounds
11:40 – that we never were capable of hearing before, and we have to invent brand new markers and brand new
11:46 – designations and brand new heart sounds and all that because we didn’t know what we didn’t know.
11:50 – Same thing with next generation sequencing. So we don’t really know what an infection eradication
11:58 – is, to go back to the testing just briefly. Because if I get just a little bit of E. coli and I’ve
12:03 – treated you and have no symptoms, you haven’t had symptoms for a month well I’m not going to
12:06 – chase that. So the negative culture is useless, but do we chase a negative PCR or NGS?
12:15 – I don’t think so. But again, the playing field is changing. These are things that are evolving.
12:20 – The same thing with the question that you ask is I don’t ever assume that an infection is not a part
12:27 – of the patient’s symptoms until I have a negative NGS. And clearly that doesn’t mean for
12:34 – you know, simple things like passing a kidney stone, which I do in urology. But even then that they can
12:40 – have an infection that’s missed because the stones blocking and we get a little bit of the bacteria
12:43 – beyond the stone. But the bottom line is for things like IC, chronic pelvic pain, chronic prostatitis,
12:50 – pain on intercourse, pain with ejaculation, pain, all these things, I never assume there’s not an
12:57 – infection unless I have a negative NGS. That’s way too many double negatives, but you get the point.
13:04 – But again, it is changing the playing field for what I see is fully 50% of my IC patients and
13:10 – probably more than 50%. I would say probably the majority, probably 55% of my IC patients
13:17 – have a detectable, significant load organism that I treat and improve symptoms. In many of them
13:24 – it’s allowed me to take them off medication. It was the problem all along, all right. Now some of
13:29 – them that fail, I scope and then we do the ulcer check and things like that. But the bottom line is
13:34 – that until you do an NGS and whether or not it’s catheterized or voided, that’s a controversy too, but until
13:41 – you do an NGS and it’s negative I don’t call it IC anymore. And I believe those criteria should change soon.
13:46 – Melissa: That was going to be the next question: If you have had patients with previously diagnosed
13:52 – IC that have been found to have infection and have subsequently been treated and symptoms have resolved.
13:59 – Dr. Hlavinka: Yes, the answer is yes.
14:02 – Melissa: One final question on the testing is, do you think it’s important to test both the vagina and the urinary tract when there’s chronic UTI symptoms?
14:10 – Dr. Hlavinka: Yes, there’s never a good doctor who won’t take more information. Now what
14:16 – we do with it is different, it may be different, but there’s never a good doctor that won’t take
14:21 – more information. And I love information and this has given me information I never had before.