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Diane Newman: Welcome to UroToday's Bladder Health Center of Excellence. I am Diane Newman, the center's Editor, and Adjunct Professor of Urology and Surgery at the University of Pennsylvania in Philadelphia. I'm very excited to have Dr. Anne Cameron, who will be presenting today a lecture on bladder irrigation for patients who have a neurogenic bladder, who perform intermittent catheterization, hence then they have a spinal cord injury. 

I asked Anne to do this lecture because I heard this lecture at a meeting, and I was intrigued by this. And there's more and more information coming out on these irrigations, and I thought I'd ask her to present some of her protocol and her research in this area. Welcome, Anne. 

Anne Cameron: Thank you very much. So, I can't take credit for the idea, or the concept of gentamicin bladder irrigation. This actually was an idea given to me by Dr. Ed McGuire, my mentor, who trained me in my fellowship. He had been using gentamicin bladder irrigations for decades before I started at the University of Michigan. And they work, they work really well, and he had never actually formally studied them. So when I suggested to him that we actually formally study this, he was very enthusiastic, because he knew that these worked well, but we were left with proving that these worked in our patient population. 

So this is the study that was published in the CUAJ. But I do remind people that this is an off-label use of gentamicin bladder irrigations. So, gentamicin is an aminoglycoside antibiotic. And why that's important is that it's a very polar cation. It's not absorbed in the small intestine or the large intestine. It's also not absorbed by the bladder. So if a patient has an augment, a colon augments, a stomach augment, it really doesn't matter. It's still not going to get absorbed through their bladder wall or through their small intestine. 

There have been several studies in children and adults following serum levels of gentamicin, none gets absorbed in the body. So you don't have to worry about antibiotic resistance because resistance develops in the gut. You also don't have to worry about the renal function or their hearing. And the concentration is very important because higher concentrations lead to better killing of bacteria. 

And when you're doing a bladder wash, you can actually use very high concentrations. Again, because you're not absorbing any of it. So this is our protocol, it's actually quite simple. You take 480 milligrams of the drug, and you dissolve it in a liter of normal saline. Patients keep a big jug in their bathroom at room temperature, and they instill either 30 or 60 milliliters into their bladder once a day. So they do this at night before they go to bed, they put their catheter in, they drain their bladder completely, they squirt this in their bladder. It stays in dwelling overnight. Very simple. 

They can incorporate it into their nightly routine, and they don't have to instill refrigerated material, because that can be very, very challenging. In people with spinal cord injury, they'll get dysreflexia, or bladder spasticity if the fluid is cold. So they do need to let it warm up. 

We will write a prescription for a month at a time. So when we did our study, what was really fascinating is that we actually saw a slight decrease in multi-drug resistant organisms. So of the patients we studied, the resistance actually went down. There was no increase in gentamicin resistance, and in those patients that we followed for six months, their UTI rate went from four UTIs in a year, or I mean in six months, to one. 

So they had a 75% reduction in UTI's, which was obviously very important to the patients. They also called us less frequently, and they had a lot less concern about their urine. So even though it was not our goal to decrease the cloudiness or the smell of their urine, it actually does improve both of these things. So patients are very reassured by this because their urine does look much cleaner. It smells much better, and patients who have incontinence into a diaper or into a pad, their urine doesn't smell as bad. And of course, that was not our goal, but it does make patients feel very happy. 

So this is not just our idea and our results. Subsequent to this, two different groups have repeated similar studies. Paul Abrams and his group looked at several patients who performed all different types of bladder management. Patients with indwelling catheters, patients who performed CIC, and they looked at their UTI rate before and after instituting the protocol. And they had very similar results to us. Of the 26 patients, they studied 22 had a reduction in the urinary tract. So this is a very good study. 

The study on the bottom by a group in the Netherlands actually studied able-bodied individuals. So not people who catheterize at baseline, and they studied people who had recurrent urinary tract infections. And most of these patients, 80% of them had multi-drug resistant organisms. And this is why they started on the gentamicin washes. And in those patients, the resistance went from 78% to 23%. 

They actually thought these patients to have infections with UTIs that were easy to treat because they were just being treated with the gentamicin. These patients were putting 80 milligrams of gentamicin in their bladder, a much higher dose than we were using. They did it every day for a month, then every second day for a month, and they decreased the dose so they were just doing it once a week. 

And interestingly, these solutions actually had sustained benefit even after they stopped the gentamicin washes. Just something interesting that I would not have predicted, but that's what they found in this study. So, at the University of Michigan, we have instituted a randomized control trial, we call it the GENIUS trial. The effect Gentamicin Intravesical Installations, and Decreasing Urinary Infections in Patients with Neurogenic Bladder. 

This is in conjunction with a physical medicine and rehabilitation program with Denise Tate, she's my co-PI on this project. And we're currently doing, this is our study design. So for the first six months, we have patients randomly allocated to either the gentamicin washes or saline, because no one has ever shown that saline is not actually the reason they're getting less UTI's. And then there's a one-week washout, and then patients are switched over to the other treatment. So, patients serve as their own control]. We're also doing a microbiome assessment... So we're getting underway with this study, and hopefully, we'll have some results to share with you in the near future. Thank you. 

Diane Newman: Thank you, Anne, for that, I have a question, because about your protocol. So when does a patient start doing the gentamicin wash? I mean irrigations, is it when they think they have an infection?

Anne Cameron: No, they're doing it every day. So every single day, patients are doing the gentamicin washes. 

Diane Newman: Indefinitely? 

Anne Cameron: So what I do in my clinical practice, I mean in this study it's for six months. But in my clinical practice, I often get patients started on the gentamicin washes, and I reassess at six months. If they've not sustained any benefit, then I certainly am going to discontinue them. But many patients start the gentamicin washes and are unwilling to discontinue them. These are people that had 15, 16 urinary tract infections in a six month period preceding admissions to the hospital with sepsis. And they start the gentamicin washes, and they have such a dramatic response, that they're very unwilling to stop these irrigations. 

I have to date not really had a patient have an adverse event with the Gentamicin washes. So I'm comfortable keeping patients on them. If a patient does want to stop the gentamicin irrigations, I encourage them to do that at six months, and we can reassess their symptoms at that point in time. 

Diane Newman: Now you're dealing with both men and women, and you don't see much difference in the two?

Anne Cameron: No, I've not seen much difference in the two... Men and women, we know the prevalence of urinary tract infections is different between men and women. But their response was not different. 

Diane Newman: Oh, okay. Well thank you, because I found this intriguing when you presented it, and I see what you're saying. Especially those patients who get recurrent. And you don't want to keep giving them the oral antibiotics, because of the resistance. So this is another way of doing it. And do you think the best though, antibiotic for this would be gentamicin? There's no other substitute?

Anne Cameron: You can use amikacin because it is also a very polar cation that is not absorbed by the bowel or bladder. I would hesitate to use something that's absorbed orally because it could be absorbed through the bladder. And then you're not doing just a bladder wash, you're actually getting some systemic absorption. The reason gentamicin is chosen is that it covers almost all urinary pathogens, but also, it's not absorbed through the mucosa. Because we all know if you take gentamicin orally, it has absolutely no effect on your body because it's not absorbed in all. It has to be given by IV, or in the bladder as a wash.

Diane Newman: Well thank you very much for that presentation.