Hello, and welcome to our live webcast, UTI's Evaluation, Evidence, and Experience. Thank you for joining us. My name is Gary, and I will be your operator for today's presentation. Before we get started, I would like to take a moment to acquaint you with a few features of this web event technology. On the right-hand side of your screen, you will see the Q&A window. To send a question, click in the text box and type your text. When finished, click the Send button or push Enter. All questions that you submit are only seen by today's presenter. Your questions will be responded to in the order in which they were received and will be addressed throughout and at the end of the presentation. At the conclusion of today's program, we ask that you complete a brief post-event survey. Please take a moment to complete the survey, as it will help us plan future web events. We are joined today by our moderator, Leslie Rickey, and our speaker, Dr. Deborah Myers. At this time, I'd like to turn things over to Leslie for opening remarks. Thank you so much. I would like to welcome all of you to our next installment of our Augs virtual forum web-based lecture series. This is a series of presentations by experts in our subspecialty from across the country focused on topics based on the FPMRS learning objectives, as well as relevant practice-related topics. The virtual format also provides Augs members the opportunity to interact with the speakers in real time. This presentation will then be captured and made available for view at any time on the Augs website. Upon completion of this program, you will be given the opportunity to provide some feedback, which we value greatly. For this evening's presentation, we are so pleased to have Dr. Deborah Myers with us here to give her presentation. She is Professor of Obstetrics and Gynecology at the Alpert Medical School at Brown University and is the Director of the Division of Urogynecology and Reconstructive Pelvic Surgery at the Women and Infants Hospital of Rhode Island. Her presentation today will be UTIs, Evaluation, Evidence, and Experience. Thank you so much, Dr. Myers, for being with us today. Thank you, Leslie, and thank you, Gary. Hello, everyone. Good evening or good afternoon for those maybe perhaps out on the West Coast. I would like to speak tonight on urinary tract infections. This was actually a roundtable presentation that I gave at the most recent AUGS meeting. It's a topic that I think we all tend to have difficulty with in our practices and a large portion of some of the patients that I see as well. I'm hoping that I can give you some strategies tonight and give you some tips and tricks, so to speak. Briefly, I'm going to just go over, in essence, the evaluation of urinary tract infections, look to some current guidelines on evaluation and management, talk about some strategies to use in patients with recurrent urinary tract infections, and possibly an office protocol management that you can use for women with UTIs as well. I'm just going to briefly go over some background information. Probably most of us are very familiar with this kind of information, but we're all well known that women have more urinary tract infections than men, most likely due to the shorter urethra and the proximity of the urethra to the vagina and the nearby rectum. UTIs do account for a lot of office visits across the country, over 7 million per year, with an economic cost of 1.6 million. Women with urinary tract infections, in particular recurrent UTIs, do have a lower quality of life. Just a little bit of background epidemiology, infants will have, 1 to 2% of infants will have bacteria, with 50% having an abnormal IVP, usually vesicle ureteral reflux. Women by the age of 24, at least a third will have had a urinary tract infection, and a lifetime risk for all women is approximately 50% of having a UTI. I think most of us are familiar with the pathogenesis of UTIs, that is the ascending spread of bacteria of uropathogenic fecal flora up into the bladder. This rarely leads to pylonephritis, though, but if pylo does develop, it's usually due to the particular type of bacteria, in other words, its virulence. But in general, most UTIs don't necessarily lead to pylonephritis. There are some host defense mechanisms that are built in that fight off urinary tract infections. The urine, in and of itself, has a low pH, and it has a high urea content. The act of voiding literally flushes out bacteria from the bladder. The lactobacilli, those gram-positive organisms, diphtheroids, lactobacilli that live in the vagina and can live in the lower urethra as well, are protective as well. Tam horsefall protein, and this is how I describe it to patients, is a protein that is produced in the ascending loop of Henle. And I describe it to patients as it's kind of like a coating or a slime that kind of coats the bladder, and interestingly does, in some basic science research, does in and of itself have its own immunoregulatory properties. I describe it to patients as that it kind of coats the bladder, and therefore the bacteria can't hitch on, so to speak, and therefore is somewhat protective. But there have been studies that have found immunoregulatory properties to this Tam horsefall protein coating. The glycosaminoglycan layer, the GAG layer, which we usually think of in terms of interstitial cystitis, also has properties that are currently under investigation, as well as what is called uroplakins, UPs. And these are kind of crystals that cover the uroepithelium and contribute to the barrier and permeability of the uroepithelium that either allow or disallow bacteria in. And there have been some studies that looked at particular kinds of uroplakins that patients with lower IPID tend to have more urinary tract infections. So there are some basic science mechanisms that are ongoing. In fact, other things that are being looked at are kind of what are the built-in immunofactors that we have in our bodies to fight bacteria. And they have looked at what we call toll-like receptors, as well. And these receptors actually recognize bacteria and can initiate an immune inflammatory response, like neutrophils, macrophages, things like that. And they have looked at different types of toll-like receptors and found that certain types make you more at risk for urinary tract infections versus not. Another factor being looked at, also, is called PTX3. And that is another molecule that has to do with immunity and that it's a pretty essential component of innate resistance, PTX3 in particular, against urinary tract infections. The PTX3 really enhances the phagocytosis of the uropathogenic E. coli. So people are looking at sort of a basic science level, what else is going on in the bladder that allows you or protects you against urinary tract infections. Things that make women, in particular, susceptible to urinary tract infections, and I think we're all familiar with that sexual activity can, increases the risk of UTI by about 60 times. That's due to the fact that there is inoculation of bacteria directly into the urethra. And for those women who have a tendency for more of the E. coli in the vagina, that puts you at risk for the urinary tract infection. As opposed to the women who have the kind of normal pathogen, or normal bacteria in the vagina, like the lactobacilli, those will not necessarily promote a UTI. I think I was, I learned in putting this talk together that all women do get somewhat inoculated with sexual intercourse, but it's the bacteria that is in the inoculation, whether it's more along the E. coli lines versus the lactobacilli, and that's what actually provokes the urinary tract infection. Diaphragm use, you know, in terms of voiding, as well as the use of spermicide, which actually knocks off the lactobacilli, also predispose women to urinary tract infections. Other things that we have heard about over the years, sickle cell disease makes someone more susceptible, renal disease, but actually there have been some studies looking at vitamin D levels. It seems that vitamin D is implicated in many things nowadays. But there have been some studies that have looked at patients with renal transplants, as well as children and infants, where low vitamin D levels have made those patients more susceptible to UTIs. How do we diagnose urinary tract infections? Well, ideally we'd like to have an accurate sampling of urine, the ideal midstream clean catch, and I don't know if you believe in a true midstream clean catch or not, but there can be obviously false positives and false negatives associated with a midstream clean catch. Obviously, the sample can be contaminated, you know, from vaginal or skin flora, causing a false positive. False negative is that the patient has already started to drink such large volumes of water and cranberry juice to kind of flush things out, and they're not giving a first voided – first morning voided sample that you could technically or theoretically get a false negative. Needing to assess the patient's symptoms, I think it's easy for patients and anyone, any woman, to not really be able to distinguish dysphoria, maybe from a vaginitis or discomfort, which might be associated with UTI, but is in fact another source of – or a vaginitis. You need to do a physical exam and some laboratory testing, which would normally be a UA-CNS. In terms of urinalysis, obviously you send off your urine for the standard UA, you know, they're looking at the color of the appearance. You can often tell by looking in the sterile urine cup yourself. They'll be evaluating under the microscopy for pyuria, bacteria, red blood cells, and your culture and sensitivity. Now, I wrote here that the criteria for UTI is 1,000 colony-forming units per ML in a symptomatic patient. I have read, though, through the literature in years past that all you needed was 100 colony-forming units. I've read 1,000, I've read 10,000, I've read various studies such that I kind of just picked the middle one for the purposes of this lecture talk. But I have seen it reported that numbers as low as 100 in a symptomatic patient would be diagnostic for a urinary tract infection. So we can maybe debate that later if someone has other kinds of information. The office dipstick, okay. So your office dipstick will, two primary things will be the nitrites and the leukocytes. So the nitrites are released by bacteria, and these are E. coli, Klebsiella, and Proteus, because these bacteria have a particular enzyme, nitrate reductase enzyme, that converts your nitrates to nitrites. So if you dip and it's positive for nitrites, that is very highly diagnostic of having a UTI, okay. I mean, if it's positive, chances are it's there, okay. However, there is a false negative rate, and the reason is that not all bacteria have this particular enzyme. And those bacteria, such as Staph, Enterococcus Pseudomonas, they don't produce this particular enzyme. So if the dipstick is positive, you've pretty much got a UTI, but if it's negative, you still really aren't able to say you don't or you do, one way or the other, okay. So the other piece of the office dipstick that we often look at is the leukocytes. And this is a product that is released by neutrophils because they produce leukocyte esterase, okay. So if the dip is positive for leukocytes, it's pretty good that you've got white blood cells, okay, in terms of even sensitivity and specificity. But in terms of predicting a UTI, more like, say, 50-50, all right. So if the dip is positive, all right, you, you know, sort of like a 50-50. If the dip is negative, chances are you don't, though, have a UTI. So the dipstick does help you, but it won't be, obviously, 100% in either direction, except the nitrites being positive. That's very predictive of UTIs, okay. There are a couple articles that have actually been published that look at the symptoms that diagnose UTI, like what are the most frequent symptoms that, you know, have been found in patients who have ultimately been found to have urinary tract infections. That is dysuria, frequency, urgency. Believe it or not, nocturia came up on that list, which I have a little bit of trouble with. But hematuria and the positive nitrite on the dip are the most confirmatory findings that will diagnose a urinary tract infection. They did talk about nocturia, and I suppose if that meant you were up and down every night, every 30 minutes, all night long, trying to avoid with, you know, not a lot of urine production, obviously, to me, that would be a UTI, but I would call that dysuria and urgency and frequency, though. But they did report that nocturia was a symptom that was frequently associated with UTIs. This kind of gets into some of the classification systems for urinary tract infections. Probably most of us have seen this before, that simple UTIs are those that occur less than twice per year. I don't see those patients too often. And the recurrent UTIs are those patients who have three or more per year, or two within six months. Another way to classify urinary tract infections is being uncomplicated or complicated. A complicated UTI is someone who has normal urinary tract anatomy, whereas a complicated UTI is someone who has abnormal urinary tract anatomy. And what I'd like to actually point out to you mostly right now is that that text or the font is highlighted as blue because it's those blue people that need evaluation, okay? So a complicated UTI, that is someone with abnormal urinary tract anatomy, would be someone who would need an evaluation, okay? Another way to classify urinary tract infections is somewhat according to the type of bacteria. So a reinfection is an infection that occurs after completion of a therapy with a totally different strain of bacteria. So the patient first comes with an E. coli. She gets treated. Three months later, she now comes back, say, with Klebsiella. You treat her. She now comes back with, I don't know, a different strain, say, of E. coli. That would be reinfection, as opposed to relapse, which is that patient that comes in with Klebsiella, treat her. Comes back again. It's Klebsiella. Treat her. Comes back again. It's Klebsiella. So that type of situation, which is called relapse, is the kind of person that needs evaluation. And again, this is in blue font or blue font text. Persistence of bacteria, somewhat similar, but it is a person who, say, comes as a persistent of the same strain from the beginning of the treatment and at the end. So a person comes in with Klebsiella, you're treating them, and they still have Klebsiella at the end. You have to start to wonder, what is going on? Why is the same strain of bacteria either keep coming back or won't go away? Superinfection, and I've actually seen this a couple times in our practice, it was during a Botox injection, of course, that the patient came in, had a urinary tract infection with a certain strain of bacteria, actually changed the bacteria during the course of antibiotics, and then required another series of a different antibiotic to treat that superinfection. So this, to me, is a situation where you have a very smart bacteria going on, or you have more than one thing going on. So again, the situations that are in the blue font, the relapse and the persistence are those that will usually require an evaluation. Going back to the uncomplicated versus the complicated kind of classifications, certain types of bacteria tend to occur in these certain kinds of situations, again, remembering that the complicated UTIs are those that have the abnormal urinary tract anatomy, but you can see that E. coli takes the lead on both, and that in terms of the complicated infections, you can see the more unusual or, you know, kind of more of the different types of bacteria that tend to be more difficult to treat, the ESBLs, Enterococcus, again, you'll also see on this slide that Proteus is written in blue, and this is if you have persistent Proteus or a lot of Proteus in a patient, they also would require an evaluation as well, too. At this point, I kind of will start talking about antibiotics. I don't see any burning questions, so I'll keep going, okay? We're going to start to talk about treatment a little bit now, and this is treatment of the uncomplicated UTI. In 2010, the IDSA, the Infectious Disease Society of America, came out with quite an excellent document, and you can get a hold of this yourself, that talked about the different treatment strategies for uncomplicated UTI, and really spoke to the fact that three-day treatments were as effective as five- and seven-day treatments, okay, and really talked about that your first-line treatments were sulfamethoxal trimethoprim, or I'll call it Bactrim. I don't have any disclosure with any company here, but your Bactrim product, trimethoprim, the fluoroquinolones, which we all know now have kind of received an FDA warning in terms of using them because of the side effects of tendon damage, but that is still possible. You could still use them possibly, but it may not be your first go-to anymore, and phosphamycin. Phosphamycin is available in the U.S. It's very popular in Europe, from what I understand, and I've even heard that it could be even over-the-counter, but it's a packet that comes as a three-gram packet, and it's something that I always keep in my back pocket for that patient who has all the allergies and your bacteria is resistant to everything, that you can use phosphamycin as a treatment. The only issue for, at least in my experience, is that the lab doesn't always, it won't test against phosphamycin unless you specifically ask them to do that, so you really, sometimes it's just, you know, you're taking a guess that this will, in fact, clear the infection. But I often use it, like I said, in my back pocket for those difficult situations. So those antibiotics are, only need three days, this is uncomplicated UTIs. Nitrofurantoin still is recommended a five-day treatment, even in uncomplicated UTI. I think most of us are probably also familiar with the fact that nitrofurantoin or Macrobid needs to be used with caution in patients who are over 65 because of renal impairment. And so I get a lot of warnings from the pharmacy now, or I get a prompt that comes up in Epic, you can't use this, you know, the patient's over 65. I did come across an article from the Geriatric Society from last year that has talked about, or talks about revising the restriction on patients over 65 and those with renal impairment. In general, if you're, the standard recommendation is if your creatinine clearance is less than 60, you shouldn't be using it. But I believe they're going to be reducing that recommendation down to a creatinine clearance of 30 because I think everyone's realized that giving Cipro and all these other antibiotics are leading to more issues in terms of side effects and resistance. So that is one thing that I came across as well. Using your antibiotic, I will tell you that nitrofurantoin is still my first go-to. The quinolones, not usually my first go-to, one because of growing resistance and the most recent FDA thing. But they do clear most infections though. I usually will go to my Bactrim as my next go-to though. And really, your choices of ampicillin are really, at least in our area, you need to check your local antibiogram, you know, from your microbiology lab. We really have a fair amount of resistance to ampicillin in that I rarely use tetracycline. Cefalothin I will use if I have to. And the sulfas, I will, the sulfa-only portion I would say, I rarely use myself as well. I will use a trimethoprine-only piece, you know, if someone has a sulfa allergy. So I still, I will say, use macrodantin or nitrofurantoin if possible. If you have a complicated UTI, this is a patient with the abnormal urinary tract, you're recommended to give a seven-day course. Now I will say that this is a large portion of my practice. I'm guessing it's a large portion of everybody else's. But abnormal anatomy, which will go through diabetes, if you had a recent UTI, seven days or longer of symptoms over the age of 65. Pregnancy, I don't really see here in my office too much. But for these folks, the 2010 recommendations were a seven-day course. So, who is uncomplicated and who is complicated? Okay? To me, this is the question. An uncomplicated person is someone who's strictly menopause-only, all right? Someone sexually active, using spermicides, family history, and they have normal anatomy. Those who fall in the complicated category are those who have a systocele, okay, diverticula, maybe a fistula, someone who's got a catheter in, someone with voiding dysfunction. In other words, they're not emptying their bladder well, they have high PVRs, they have detrusive sphincter dyssynergia, they don't void because of levator spasm. Not so much common in my practice with urinary tract obstruction, except a kinking at the bladder neck from a large systocele, or someone who might be considered to be immunosuppressed, such as someone with diabetes. So, I don't know how everyone else's practices are, but I would say majority of patients I see fall into that complicated category. What sort of history, when you are talking to a patient, would prompt you to require, like, oh, this lady's going to need an evaluation? Obviously, someone who's had a prior urinary tract surgery, particularly a sling, is a sling in the bladder, you have to think about prior pelvic malignancy, someone with gross hematuria, history of bladder or kidney stones, someone who might have immunocompromised, such as diabetes, sickle cell, history of diverticulitis, especially a diverticular abscess where you've now created a colovesical fistula, and someone with, obviously, frequent pyelonephritis. So, these are things out of history taking that would prompt you to have the patient undergo an evaluation. What things on a physical exam do you think that you're going to find need to prompt you to do further evaluation? And obviously, diverticulum, again, maybe a Skeen's gland, because it might be a divertic, fistula, prolapse, incontinence, and large PVR, so there's our world. What things on results might prompt you to have the patient go for a further evaluation? Someone who you find the elevated PVR or find has voiding dysfunction, those particular kinds of urea-splitting bacteria, such as Proteus and Yersinia, someone with asymptomatic microscopic hematuria we would work up as well, and those who have those recurrent UTIs with that relapsing and persistent bacteria. What is your evaluation going to entail? Most likely to include cystoscopy, there might be some other type of imaging, if you're thinking of divertic, urethral divertic, I should say specifically, or you can even have a bladder divertic, I've seen that as well, where you might need your MRI, I don't know if anyone does double balloon urethrograms anymore, but we still do, you might need ultrasound to look at urethral anatomy, you might need urodynamics to look for that voiding dysfunction, upper track imaging, I've not seen any clear guidelines on this, but it would comprise either renal ultrasound or renal nephrogram, you know, without and with IV contrast. You know, if I had somebody who I was really worried about stones or, you know, microscopic hematuria, I'd probably go right to the CT, you know, if it's kind of like a just a, you're not really thinking that, I'd probably go for a renal ultrasound first, so I would have to use discretion in which upper track imaging mode to pursue. So let's get to recurrent UTIs, because I think this is most of, I'm sorry, I have to step away, I got my lights automatically turned off, so I'm now sitting in the dark, I have to go wave my hands, hang on a minute, there we go, sorry, all the green lights, all right. Recurrent UTIs, once again, three or more infections per year, this is about 25% of the women who do have UTIs and it comprises 50% of office visits. Again, the kinds of infections, those that relapse or have persistent bacterias are those who would require evaluation. Why would someone have recurrent UTIs? Well, the bacteria are increasingly developing resistance, perhaps the drug isn't getting concentrated into the urine, maybe the patient's not taking all their medication, or they're in fact an underlying structural abnormality. Another theory that is, I don't know if it's necessarily a theory anymore, but there is a lot of discussion and research looking into these pockets of bacteria that get, if you want to say, embedded or within the detrusor itself. There are thoughts that reinfection is actually due to the fact that, say, the E. coli actually get into the urophelial cells and form these bacterial reservoirs, and that is these quiescent reservoirs that constantly lead to reinfection, reinfection, reinfection. I also, interestingly, came across some literature that looks at maybe the chronic nightly antibiotic use to prevent UTIs may be promoting this type of situation as well. So that was a little bit eye-opening for me. But people are looking at these bacterial reservoirs as a possible source of recurrent UTIs. In terms of treatment for recurrent UTIs, if you do find underlying cause, obviously treat it, okay, like the divertic or the bladder stones, kidney stones, whatever that are chronically infected. But if no cause is found or if you do have a cause but need something in addition to, you can start to use these kinds of strategies. I went through a lot of Cochrane reviews, I will say, and some review articles to try and get a summary of all the evidence that are out there for a lot of these treatment mechanisms that we use often. I found that in terms of behavioral recommendations, there is good evidence for saying do not use the diaphragm, do not use spermicide, but really very weak or insufficient evidence for the wiping front to back, which I still can't hardly believe wouldn't be a good idea, but anyway. Avoiding after intercourse, adequate fluid intake, regular voids, hot tubs, douching, tampons. So really not a lot of good evidence for those things. Vitamin C, okay. One thing that I have done in my practice has been prescribing vitamin C, usually 500 milligrams twice a day, in thinking that it would be acidifying the urine. Well, it really, 500 milligrams twice a day really doesn't acidify the urine very well. And it really isn't probably the mechanism. I did come across some weak evidence that does support the use of vitamin C. However, the thinking is actually more along the lines that the vitamin C works by reducing urinary nitrites to a reactive nitrogen oxide that actually causes quicker bacterial death, okay. So it is actually the vitamin C that kind of promotes this release of nitrogen oxide that actually subsequently kills off the bacteria much more quickly. So there may be some evidence, and this might be a possible mechanism of why vitamin C may work, okay. But there's really not a good amount of literature out there at this point. But there has been some basic science stuff along these lines. Good old cranberry, okay. Cranberry pills dose 500 milligrams three times a day. You need at least 36 milligrams of the proanthocyanidin, the PAC, the active ingredient to inhibit the pili of the E. coli, okay. So there's a fair amount of evidence out there, but it is conflicting, okay. In general, from my readings, is that juice really doesn't work well. If you're going to do anything, you use capsules. Now I know we had the recent JAMA article come out this past, was it this summer, I think, or recently, just in the fall, where there was a study that looked at oral cranberry capsules, and that study actually did have an adequate amount of the PAC. In fact, they had 72 milligrams, okay, as opposed to the need of 36. They did a, you know, trial with cranberry versus placebo. It was in a group of patients who were mid-age of 86 who kind of had, I think, chronic bacteria with pyuria, and I don't know, maybe the patient population maybe wasn't the best choice, but it didn't really show any advantage to cranberry capsules in that particular patient population. But my experience is, and I'm sure all of you have some patients who do well with this, and, you know, would support it at least on an individual level. But I think still more needs to be studied for cranberry. D-mannose, these are all these kind of over-the-counter treatment strategies I'm going through now. The dose is 2,000 milligrams a day. There are some studies, like on the basic science level again, that have looked at the ability of D-mannose to inhibit that adhesion of the uropathogenic E. coli to, you know, the inner surface of the bladder. There are some limited clinical studies that do show reduction for recurrent UTIs. D-mannose may not be effective against other kinds of bacteria, you know, because they may not have that PILI adhesion factor. So I do have found that sometimes D-mannose, 2,000 milligrams a day, does help some patients. I actually find it more helpful than cranberry now. Probiotics, okay. My readings on probiotics pretty much have stated that oral probiotics really don't do much. If you're going to use any sort of probiotic, it should be intravaginal. And there have been some limited studies that have looked at the use of vaginal probiotics. This was one in particular on premenopausal women. It did seem to reduce the rate of recurrent UTIs, although it wasn't statistically significant. So I think if there is a recommendation for probiotics, it probably should be intravaginal probiotics. Those are actually hard to find. I actually went to my local CVS the other night, Rite Aid, and just went to that aisle in, you know, feminine sanitary protection products. It is eye-opening what is there. And I would probably recommend it for all of us to go just take a look to see what's out there. But there are some intravaginal suppositories right on the shelf. I happen to have a brand here that I found online called FloraFem. I mean, I don't have it in, you know, any reason to recommend it in particular. Just it was one of the brands that, one of the few brands that was actually intravaginal. Most are oral. But they talk about it being used for replenishing vaginal flora, which, even though it was taken orally. So most of the research that supports probiotics is on intravaginal suppositories. So what good evidence is there? Actually estrogen vaginal cream. There is relatively good evidence for this. We all are aware that atrophy can lead to increase in vaginal pH and promotes the colonization of the vagina with uropathogens such as E. coli. Therefore treating with vaginal estrogen cream should be a benefit. There have been some randomized controlled trials that do show a reduction in the number of recurrent UTIs as also one by Shlomo Ras and Stam that compared cream versus placebo as well. So vaginal estrogen cream does have fairly good evidence. Okay. Kind of getting into some treatment strategies. I'm sure many of us are familiar with some of these as well. But those infections that are related to intercourse, the use of post-coital antibiotics, the single tablet can be given pre- or post-coitally, treats that inoculum of bacteria, the antibiotic often recommended is nitrofurantoin, could be a Keflex, could be a single dose Bactrim. Here one dose is all that is needed and shows actually pretty good evidence that post-coital prophylaxis has similar efficacy as giving continuous, like nightly doses of antibiotics as well. So that is good news, okay, that post-coital would work as well as nightly low-dose antibiotics. Another way to have your patients manage their urinary tract infections is to get them on their own self-start program. If you have a patient in particular who, you know, is fairly resourceful, I've actually taught people how to use a dipstick, okay, you give them their three to five-day course of antibiotics. Once again, we've been over these, nitrofurantoin, like I said, is my top if possible, quinolones, be careful now with the most recent FDA warnings, and your trimethoprim, trimethoprim, sofoxamethoxyl, your Bactrims. If symptoms aren't resolved, then that person needs to be seen, you know, and get a UACNS, so the self-start treatment. The prophylactic antibiotics, in other words the continuous low-dose, usually given at night as most people are not up at night emptying their bladder, so there's a better chance that the antibiotic will be concentrated into the urine. But I use this, so you have some, you've been following someone with recurrent UTIs, you're now on their fourth one, you've got to treat that infection and you put them on the nightly dose. Nitrofurantoin, once again, does not affect fecal flora, the other ones do, but with a low dose, the hope is not to affect it as much in terms of developing resistance. So a 250 mg cefalexin, Bactrim single strength, trimethoprim 100, I will treat patients for a solid six months. I will tell them it will not be perfect, you may have an occasional infection, it doesn't mean that it is a failed treatment option for you, but hopefully we will reduce the number of recurrent urinary tract infections. I will tell you also that I've had patients on nitrofurantoin for long periods of time, one year, two years, I do get a periodic chest x-ray to make sure there have not been any lung changes that can occur with chronic macrodantin use. I have seen it twice in my time, so it's not common, but it does occasionally happen, okay? Methanamine salts, brand name that I'm familiar with is called HIPPREX, this is an oral medication, I'm sorry, I don't have the dose here, I just realized, it's a 1000 mg twice a day, but I have had some patients just take one a day. This is hydrolyzed in the urine to form ammonia and formaldehyde, which sounds nasty, but formaldehyde is very bacteriostatic, I describe it to patients as, it's not really necessarily antibiotic, but it's kind of like a cleansing wipe, okay? There is some evidence out there, okay, not a lot, and it's not super evidence, but there's some evidence. In a Cochrane review, though, that it was shown that methamphetamine HIPPREX might be effective for recurrent UTIs in patients who don't have anatomic abnormalities, it has been shown, however, that a nightly low dose of antibiotic is more effective than methamphetamine salts, that makes logical sense to me, because you're giving an antibiotic as opposed to something that is just bacteriostatic. So there is some evidence out there for HIPPREX, okay? This is a kind of a flow sheet or algorithm, I think I should have it up there available for you to download as a handout, I can't claim fame to this. I did adapt it from Duane Hinckling's and Vic Niddy's figure that's in one of their review articles, they have an excellent review called Management of Recurrent UTIs in Healthy Adult Women, published in 2013. I have added some things into it, though, to kind of help remind me of, you know, alternative over-the-counter kind of options as opposed to, you know, antibiotics. So you're welcome to use that and adapt it as you wish. So you have your new patient coming in with recurrent UTIs, and these are ways that I have developed and trying to implement in my practice here to reduce the number of phone calls, okay? I give that patient a standing order for UACNS, usually it's monthly and most labs take it for up to six months. I recommend a lab so I can get the result right into our electronic record. The ICD-10 code is R30.0, my favorite code, which is dysuria. If I have a patient who I think can learn how to use a dipstick, I'll teach them how to do it, give them instructions how to do the cling catch. I give them a sterile urine cup in one of those bio bags, okay? And I give them prescriptions. I give them prescriptions for either, you know, three to five or, you know, seven days depending on the person and the situation. And I also provide them with antibiotics and phenylazopyridine, or what we know as pyridine, where they can go over the counter and get azo for travel. So this is one thing that I find. I think they feel like they're enabled and can also help get them treated more quickly and efficiently. Creating a patient handout. I still think emptying your bladder every three hours is probably a good thing. Sit and empty completely. I still think wiping front to back is a benefit, okay? Obviously, avoiding after intercourse, avoiding the spermicides, and kind of a laundry list of all the over-the-counter products that patients might be interested in or want to pursue. Just a couple things. We're starting to get close. We've got about ten minutes left. I'm pretty much getting close to the end, though. Just to kind of touch on a couple other things, is there a vaccine? There is urovaxilm available in Europe. It's an oral vaccine. It has 18 E. coli strains in it, and there have been some studies out there looking at the efficacy of this vaccine. Unfortunately, a lot of the studies were not very well controlled, so it was hard to really get a good sense of whether or not this vaccine is effective or not. There are some meta-analyses that do show that this vaccine did reduce the recurrent UTI rate compared to placebo, so there is some evidence that this vaccine may be effective. There is a vaginal suppository vaccine, as well, called SoCoUroVac. This is made, actually, in Switzerland, and this contains very similar strains as to the oral vaccine, which I just mentioned. There are some studies out there that do suggest moderate efficacy in this, but these patients needed a periodic booster, so to speak, like every four months, in order to maintain effectiveness. So there are some things on the horizon. What other kinds of new things are out there? There is actually research looking at Ferscolin. I don't know how many of you are familiar with Ferscolin. Apparently, it's a herbal supplement made from the plant coleus that's used for weight loss, but Ferscolin has a property of increasing cellular activity, and they've done some basic science studies in mice looking at Ferscolin to purge those reservoirs of E. coli that are embedded and that are buried in the bladder wall. So who knows? Maybe that'll be something that'll be on the horizon. Rebuilding the GAG layer, there's a randomized trial looking at the use of hyaluronic acid and chondroitin sulfate versus placebo, and then doing installations of this solution over six months reduced urinary tract infection rates as well. There was a product out many, many years ago that we used to get from Canada for interstitial cystitis called Cystistat, and this is what this kind of reminds me of. Asymptomatic bacteria, I think we see a fair amount of it, especially in our older population of the patients 80 years and over. About 25 to 50 percent of those patients will have chronic asymptomatic bacteria. This is bacteria without symptoms, that's the key word there. I will tell you the bottom line in general, don't look and don't treat. There are some instances where you do need to treat your asymptomatic bacteria, and that for me will be someone who I'm taking to the OR, who I'm going to be doing a procedure on. I did come across an article of intradetrusor Botox in patients with untreated asymptomatic bacteria, and really with no downside, I mean no adverse outcomes. So they had patients who were getting Botox in the bladder who had asymptomatic bacteria and were not clearing that bacteria. I don't know, I'd be curious to know if anyone else had any experience with that, of not treating them as well. Catheters, just very briefly, there are some patients who do need to do clean intermittent self-cath, who do get UTIs with self-cath. You can use a low dose antibiotic, you could use your methanamine salts again. For those patients who have indwelling catheters, basically antibiotics are not effective long-term. They might be helpful in short-term use, but I know there have been studies years back in our, you know, presented in our society that catheter use less than seven days really doesn't require antibiotic coverage. And there was a lot of interest years back also about the different kinds of catheters, you know, whether they're coated with nitropherozoin or silver-coated, but these catheters do decrease the rate of UTIs if they're in place less than seven days. In conclusion, I'll just wrap up here because I see we have a few questions. The workup for these patients needs to be, for those who have that relapse or persistence of bacteria, that complicated patient, know your microbiology lab antibiotic profile. Hopefully I've given you some recurrent UTI treatment strategies, both that involve antibiotics and those that don't, and hopefully how to manage some of your office phone calls and protocols as well. I will stop there. It's been pretty quiet. This is, so there are a few questions here, Deb, if you don't mind if I read some of them out. I do want to say there was one statement that with regards to the JAMA study, there were only five chronic UTI patients in that, but I would just encourage all of you all to look at the inclusion and exclusion criteria in that paper carefully. We have a question from Dr. Lasalo, which I think is a situation we probably all come up against. There is an older woman who is told she has a UTI because at her annual exam, her UA showed leukocytes and urine culture had endococcus. Her PCP tells her she has a UTI and treats her with Cipro. Patients state she had no symptoms at all. So what do you do with asymptomatic positive cultures, which I think you said don't look so well, but not everybody does that. The PCP and the patient's family are worried about this patient getting pilo from this untreated asymptomatic bacteria. What would I do in that situation? I mean, well, there's a couple things. Granted, she probably has asymptomatic bacteria that probably didn't need treatment, granted. However, now you're in the situation, the patient's in your office, and the family's probably looking at you. My guess is there probably will also be some element of abnormal urinary tract anatomy. Maybe yes, maybe no, but there's likely to be a cystocele or an elevated PVR. I mean, obviously, you're going to do a history and a physical and probably check a PVR to see if there's anything else underlying going on that would require an evaluation or workup. If you do find something, you probably would pursue. But then ultimately, the need to treat that patient down the road, I would basically try and educate that family and the patient that continual treatment with antibiotics, we're going to be going nowhere. I mean, there'll just be continued colonization. I would probably try other strategies to maybe try and reduce the over-the-counter kind of products as well that we briefly went through. I mean, I would not put that patient on nightly antibiotics, you know, something like that, because then you're going to be growing resistance, and then you're chasing your tail. Yeah, I would agree. I also sometimes in these situations will counsel them about the side effects of the antibiotics themselves, and I find that people seem to be more responsive to that, you know, maybe than they were 10 years ago. So that can be helpful too, especially in an older person. Those risks aren't small. Okay, so we have another question. Can you comment on the emerging evidence of the urinary microbiota and how this may change lab evaluation and treatment? And I know there is actually some kind of commercially available group that was at a meeting recently where they're saying, you know, you can send in your urine and they'll spit out the 100 different kinds of bacteria that were there. So what do you think about that? Yeah, actually, this kind of gets a little bit, at least in my experience, into interstitial cystitis. Because years back, even, I don't know, 15 years ago, there were labs that would do these extended cultures, used to send your urine out to Colorado, and they would come back with this whole profile of bacteria. I think this is going to be very interesting for us. I think, you know, the fact that we always said the urine is sterile is not necessarily – it's not true really anymore, and it's like a microbiome. I think we need to obviously get more information about, you know, what is a normal microbiome. And we've looked at – there have been some studies looking at in terms of, you know, OAV. We're actually starting to look at this related to interstitial cystitis here. I don't know – I actually have not come in contact with any commercial labs, but I'm sure they are out there. But how do you manage that patient, and does it mean anything yet? I mean, I'd be – I'll take anybody's input on this. You know, what do you do with that information once you get it? You know, that's the question I have. Yeah, I know. I totally agree, and that was what I asked the company. And I think there's – obviously, it's going to be very, very useful in the future, but I think we're still kind of – still have the clinical relevance or how to interpret those findings or how to use it to treat our patients just yet. All right. So, I think I have two more questions right here, so I'm going to get to them real quickly. And you sort of touched on this next one, I think, a little bit, but regarding the FDA warnings against Cipro and pulmonary fibrosis with nitrofuran tolerance, what supplements do you recommend to young people to prevent pericoidal UTIs if you don't want to use antibiotics? If you don't want to use antibiotics, oh, that's interesting. I don't know if I have done that. I suppose you could – I suppose if I would do anything, I probably would use the methanamine, excuse me, as opposed to the cranberry and – I don't know if D-mannose would work on such a quick basis, you know what I'm saying? Right. Yeah. You would have to – I mean, to me, the thing with intercourse is that it's an inoculum that needs to be cleared. And I'm just trying to think that if something – I don't – actually, I don't know enough that – would the cranberry be something that would – does it need to be there longstanding to be effective, if it's effective at all? But I would think that probably the methanamine might be something that might be more quickly, you know, secreted into the – you know, processed into the urine and be more bacteriostatic. I still use nitrofurantoin. Like I said, I have – I shouldn't probably say this, but I've given it for patients for years. And I do get, like I said, a periodic chest X-ray. I have very rarely found chronic lung changes. So, I mean, I'm not saying it can't happen, but, you know, if you monitor them – but sometimes the internist pulls them off on you, so you may not be able to use that long-term. True. Okay. Okay. So, what do you do with a woman with persistent urethral burning following UTI treatment with a negative test of cure? This is a study that needs to be done. Thank you. I see this a fair amount, okay? And what I think goes on – I don't have any proof, this is my own conjecture – is that obviously they get a urinary tract infection, they got E. coli or whatever. You treat them with whatever, your Cipro or Bactrim, whatever it is. And then they are still symptomatic even though that urine will be negative. And what I have described this to them, the patient, is that I believe, I think what might be going on, is that inner lining, your gag layer gets kind of inflamed, beat up, whatever, and that it takes a while for the bladder to heal. So that's how I describe it to patients. So I kind of treat them like an IC episode at that point, where it's increased fluids, pyridium, I use my baking soda thing, you know, and just try and get them through those last few days. And usually they do resolve on their own. I kind of use the same concept, that it's the accurate signaling that got ramped up during the UTI is just taking longer to calm down in some people. And so it's not truly due to, it's an inflammatory state versus an infectious state. It's almost like a post-UTI syndrome almost, that's what I find. Okay. Well, I think we have to stop there, we're about four after the hour. So I just really want to thank Dr. Meyers for that great presentation. I think we can see from all these questions, this is something that we're all dealing with and it's a challenge for everybody. I think this would be a great topic for a panel at one of our upcoming meetings, actually, because there's always so much feedback. And so, oh, go ahead, I'm sorry. No, no, no, I find that, you know, it's not like surgical, you know, stuff that we do, but it is an issue that we deal with in our office on a daily basis, so. Well, and it takes lots of resources. It takes your resources, your fellows, your office staff, and it's an issue, you know, because there's a lot of patients with these issues and with the segment of older Americans increasing, it's only going to be getting worse. And unfortunately, we're still kind of treating people with the same treatments we've had for the last 50 years. So, but anyway, that was great. I want to thank everybody also who was on the call and for participating, for carving out time in your days to be here also and to be so interactive tonight. Again, if you missed it at the beginning upon completion of this program, you'll be prompted to provide feedback, and please do. I do want to tell everybody we are looking forward to our next program on December 14th, again, at 7 p.m. Eastern, 6 p.m. Central, 4 p.m. Pacific. We're going to have Dr. Adam Holtzberg talking on the patient experience, CGCAHPS, and physician communication, and for you all that don't know, that's a new standardized tool to measure a patient's perception of care provided in the office setting. And as we know, some of these tools are going to be used, we think, we'll see what happens with healthcare, but used increasingly likely to become part of reimbursement formulas for physicians. So I'd invite you all to register for that as well. So thank you again, Dr. Myers. Good night, everybody, and we will look forward to seeing you all next time. Thank you all. Thank you, Leslie. Thank you, Dr. Myers. Thank you, Leslie. On behalf of AUGS, I'd also like to thank everyone else for your participation in today's event. Again, a post-event survey will appear shortly. Requesting your feedback, please take a moment to complete the survey as it will help AUGS plan future web events. This concludes today's program. Again, we thank you, and have a great night.

UTIs

Evaluation

Evidence

Deborah Myers

Management

Recurrent UTIs

Antibiotics

Behavioral recommendations

Urinary microbiota

Asymptomatic bacteria