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Another UTI?!: Management of Recurrent UTIs in Non ...
Another UTI?!: Management of Recurrent UTIs in Non ...
Another UTI?!: Management of Recurrent UTIs in Non-pregnant Women
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Hello and good evening and welcome to tonight's webinar. My name is Dr. Christina Lewicki-Kauff and I'm the moderator for today's session. Before we begin I'd like to share that we will take questions at the end of the webinar but you can submit them at any time by typing them into the question box on the left-hand side of the event window. So today we're going to be talking about another UTI, management of recurrent UTIs in non-pregnant women, and Dr. Cassandra Carberry is our guest speaker. She's an assistant professor, clinical educator in the Department of OB-GYN at Brown University and she's a member of the staff at Women and Infants Hospital. She joined the Brown faculty in 2009, graduated medical school from the University of Texas Health Science Center in San Antonio. She then went on to NYU to complete her OB-GYN residency and fellowship in FPMRS. She is the director of clinical services for the Division of Urogynecology and Reconstructive Pelvic Surgery and plays a crucial role in ensuring that the division applies best practices and promotes patient-centered care. She is a committed educator with multiple awards for excellence in teaching. She has also served on the Guidelines and Documents Committee of OGS from 2013 to 2018, contributing to the publication of numerous documents including being the co-lead author with Dr. Linda Brubaker on the OGS best practice statement on recurrent UTIs in adult women. Hence, we have asked her to host tonight's webinar. In her clinical practice, Dr. Carberry offers her patients a wide variety of treatment options both surgical and non-surgical for pelvic floor disorders. And as a friend and a colleague of Dr. Carberry's, I'd like to thank her from the bottom of our hearts and we're looking forward to our webinar. Go ahead, Cassie. Thank you so much, Dr. I appreciate the kind introduction and thank you to OGS for inviting me to do this. It's an honor and thank you to everyone who is attending. This is great. So hopefully it'll be helpful. We're not going to be able to talk about everything in this category and we have narrowed it down to non-pregnant women and mostly we'll be concentrating on recurrent UTIs that don't have complicated features just again because there's so much to cover. I have no disclosures. I'm beginning to feel like that's actually not a good thing but there we are. As far as our program for tonight, I'm hoping that we'll be able to cover some ground and start with making the diagnosis and distinguishing it from other entities. Sounds straightforward but as we all know who take care of these patients, it isn't always easy to make the diagnosis. When to perform further evaluation. It's also, there's not a lot of data to guide us about that and so we'll talk about what what we do know. Sorry, looking also at preventative measures, what has been proven, what's not, what's kind of on the horizon and I want to spend a little time talking about things that more novel maybe not as established in terms of the evidence but seem pretty promising and so we'll talk about it. So starting with definitions, there's always variation but generally the most generally agreed-upon definition of a urinary tract infection is an infection in the urinary tract based on both symptoms and a pathogen in the urinary tract. A widely accepted definition of recurrent UTI is two culture-proven infections in six months or three in a year. Again, there are variations but this is the definition that most people will accept. As a kind of sub-grouping of recurrent UTIs, some people like to further classify things as either a relapse which is specifically the detection of the same pathogen causing symptoms within two weeks of an appropriate course of antibiotics versus recurrence which is finding an infection two weeks out from treatment or more or in that same in a closer time window but by a different pathogen. I don't know how clinical those terms are. I think that the pattern of infection is very important and is part of what will help you manage these patients over time. Whether or not those specific labels, I think there's some debate about how useful they are. In that sort of same discussion, the question of whether or not you need to prove that there has been, you know, eradication of the pathogen before moving on is a question. I mean, there in my career, I would say I feel like I've been indoctrinated that asymptomatic bacteria should never be treated except in pregnant women but in developing the best practice statement there we, you know, among that group there was definitely differing opinions about the utility of sometimes checking a culture to see if there was resolution at least microbiologically. I think I usually use symptoms to define whether a UTI is resolved but in terms of under long-term understanding of what the microbiologic pathology is, I think that is some utility to that. I think the challenge becomes, of course, in a patient that you have treated, if you now test them again and their culture is positive but they don't have symptoms, what are you going to do at that point? And that's really the hard part. And so the question becomes, is asymptomatic bacteria in patients who have recurrent UTIs the same as in patients who have sporadic or episodic UTIs? These patients are really not the same in many ways and so can we say that? There's not a lot of data to help us here. There's one study that I'm highlighting and sorry, I don't know what happened to my formatting here that looked specifically at the question of treating asymptomatic bacteria. And they did look at a group, they did look at the data which was only one RCT, but it was a large group of recurrent UTI patients and they did not find that it was helpful to treat the asymptomatic bacteria. In fact, it increased the risk of developing a symptomatic UTI. And there's other kind of evidence on a microbiological level that eradicating those pathogens might actually allow, or eradicating those bacteria might allow for the presence of actual symptomatic UTI-causing pathogens, so they might actually be protective. And then in specific, I'd also be interested in elderly patients, postmenopausal women, treating them again was not helpful. It did not decrease the rate of asymptomatic UTI, it's not helped resolve even the presence of the bacteria. But as you can also see, the quality of evidence is not great and that is because of either the volume of studies in the case of the recurrent UTI group or the type of study design. So I would say that that question is still not completely answered and so you have to kind of decide for yourself if you feel like clinically that's going to make a difference. Epidemiology, we'll go over, I feel like it's kind of we have to we have to talk about that a little bit. As with any condition, it varies with the definitions that that is used, but needless to say, urinary tract infection is a big problem. Eight million ambulatory visits a year, almost a quarter of which are presented in the emergency department, and that's really problematic. And some of that, you know, also points to the fact that these can be very, very detrimental to patients. It's not something that should be, you know, we say, oh UTI, it's not a big deal. In the patient experience, it is pretty significant and disruptive to their life. There was a study looking at all comers, men and women, about 30,000 patients and they reported these UTI rates annually and you can see that for across ages, the rate is about three to five percent, but if you look at a more specific populations higher and a two percent of women have recurrent UTIs, so that is pretty significant. And again, we also know that a third to nearly a half of women who have one UTI will have another and 50% of those, if that second episode occurred within six months of the first, will have a third episode, therefore setting up this pattern of recurrence. And there are studies that show that women with recurrent UTI have worse quality of life, standardized questionnaires, more depressive symptoms, and higher rates of sexual dysfunction. So again, these are, this is definitely something that the patients are affected by. I mean, I feel like I see more patients in tears over recurrent UTIs than maybe other problems. It's pretty significant. Pathophysiology is what we want to talk about next. So what we, what we think we know now, which is, I will say at the get-go, based on standard urine culture techniques, and that may or may not be enough, there are a lot more studies that are using culture-independent techniques now to really establish what is the urinary microbiome, where we thought for many years that urine was sterile. It seems to absolutely not be the case, but the question is understanding what is normal and what is abnormal, and what's indicative of certain, certain conditions versus others. So in general, from what we know, you know, today, the pathogens that we see causing infections are from the neighboring organs. So the urethra is near the vagina and the rectum, that's just the way it is, and so that's where we're gonna see the flora coming from. And in recurrent UTI, it's the same, same suspects as you would have in episodic UTIs, so E. coli being the absolute most common, Klebsiella, Proteus, Enterococcus, you'll see all those two. However, in recurrent UTI, you are more likely to see resistant organisms, and even though non-E. coli pathogens are not more common than E. coli, they are more common than they would be in episodic UTIs. And I want to, I'm gonna make this point several times, and maybe it's too much, but I just want to start by saying that patients feel really bad when someone tells them that they have an E. coli UTI, or I've certainly had patients say, oh my doctor told me it was, there was stool, there was stool in my urine. They immediately feel responsible for this, they immediately want to spend, you know, a lot of time telling you how they're not, you know, they're hygienic, they're clean, they're doing this, they're doing that, they're definitely, they don't know how this could possibly happen, and this is your first opportunity to dispel that myth. It's normal to be in the area, it's not because they're dirty or doing something wrong, necessarily, and that, you know, is, is, goes a long way. I mean, I've had many patients who have described the lengths that they go to, including things like taking a bath in bleach, which you don't want them to do. So, you really want them to understand that there are bacteria in the area, and that's not anyone's fault and it's normal. So, the E. coli that become problematic are referred to as uropathogenic E. coli. So, these E. coli have special properties that make them really good at staying there. So, they have some special, special features like certain types of flagella, adhesions, things that make them stick to the, stick to the urethelium. They also may get intracellular, so they're able to enter the cells of the urethelium and form what are called intracellular bacterial communities, which is definitely not as nice as it sounds. You may also see the term quiescent intracellular reservoir, and those are basically these storage sites for the E. coli that are what allows these recurrent infections to happen. So, this is just a little cartoon of what we think is going on. So, if, if you have uropathogenic E. coli, it's able to easily adhere to the surface, then potentially invade the urethelium, replicate and create these intracellular bacterial communities, and that is providing the source for recurrent infection. So, we'll talk about risk factors. I think there's always this compulsion to talk about, you know, hygiene, and, and I don't, I find that it's actually a rare problem with patients. Most women know how to wipe after they have a bowel movement. That's not really, that's not really the problem. I mean, you're welcome to go over that, but again, I would definitely be clear to the patient that it is not their fault, because that is, that is something that patients will want to explain themselves. So, in terms of actual risk factors, things that, you know, there are a lot of things that we have identified as risk factors that we really can't do much about, and there's very few things that we can modify, so we do want to focus on those. So, if the patient is, herself has had a UTI at a young age, that seems to be a predictor for recurrent UTIs. Having a maternal history of UTI, and in fact, any first-degree female relative, there are certain genetic things like certain blood group antigens that seem to be associated with these, your, your pathogenic E. coli being very adherent. You read a lot about sexual risk factors, which have been more commonly looked at in pre-menopausal women, including new partners, frequency of intercourse, and spermicide use. I would say don't forget about sexual risk factors in your post-menopausal patients, even though that's not primarily where those have been studied. Of course, spermicide is not going to be an issue for those patients, but, you know, there may be a pattern related to intercourse, and you don't want to miss that, because that may give you an option for prophylaxis, as we'll discuss later. So, other things that are, you know, potentially modifiable, urinary incontinence is a risk factor for developing UTIs. Surgery for stress incontinence after a mid-urethral sling, there's been about 2% reported risk of recurrent UTIs, and vaginal atrophy is probably one of the most important things that we can address, and sometimes that's the one thing that no one has tried for the patient who's presenting to you, and that's kind of nice, because you can do that fairly easily. So, again, making this diagnosis seems straightforward, but is obviously not. You do have to have the two elements, the symptoms and the pathogen. So, to find the pathogen, you're going to do a UACNS. It's not necessary for episodic UTIs. Sometimes people say, well, you know, why are we treating all these UTIs over the phone? That's totally fine. If you're a person who has a UTI once every five or ten years, you don't need to go to a lab. The problem becomes that person calls, and then they start calling every couple years, or then they start calling every couple months, and no one is picking up on it, and that's the problem where no one is seeing that there's a pattern because they're just getting treated over and over. So, that is sort of a message more for our primary care colleagues that, you know, pay attention to when those things are happening, and it's fine, again, to treat people without, you know, a culture in that situation, but once they become, they're in this realm of recurrent UTI, it's a different situation because that is really going to help you manage them in the future. It's also necessary to make the diagnosis. As far as symptoms go, dysuria is absolutely the most pathognomonic symptom for UTI. Frequency, urgency, hematuria, suprapubic pain are also in the list, but dysuria seems to be the most specific. In fact, if you have a patient who's premenopausal with dysuria and frequency, and she's not describing any kind of vaginitis type of symptoms, then there's a 90% chance that she does have a UTI. So, again, this kind of goes back to that idea that patients know when they're having an infection, so they can call and you can prescribe that to them. Again, patients are not the same as patients who do not have recurrent UTIs. The other thing that happens, which makes it not straightforward, is I feel like it feels like 99% of my patients say, oh, I never have the burning. I never have the pain. It's always XYZ, and that's when it becomes harder to discern. Is this really a symptom that is associated with a UTI, or is this, you know, a coincidence, like some other symptom that you also have, but has nothing to do with the fact that you also happen to have a positive culture at that time? So, you know, acute onset dysuria, frequency urgency, even new onset urinary incontinence have been found to be associated with UTIs, but whether or not worsening incontinence, worsening frequency and urgency, is that a telltale sign of a UTI? Not necessarily. I generally, in my practice, I find that because a lot of my patients are already having urinary symptoms, if they do notice a change, I would probably err on the side of using that as a diagnostic symptom. However, this is again where watching your patients over time is really helpful, because if you find that you treat them and those symptoms do not go away, and you establish, you know, that despite treatment, there are those symptoms, and you can feel a little bit more certain that that's not part of an infection. Mental status and personality changes in our elderly patients is among, I think, the most challenging in terms of what to do with that information. You will undoubtedly, if you're seeing these patients, you will have patients who either report to you, or they're more likely their caregiver reports to you that they, you know, I know when she starts acting this way, or she starts forgetting things, or she gets really low energy, they always test the urine, it's always positive, she gets treated, and she is back to normal. I think it's really, it's really not clear. I've discussed this at length with my geriatrics colleagues. There's no, there's no real consensus. I think that, again, this is one of those situations, and we'll talk about it more later, where the pattern overall, what you have, when you follow these patients out, is going to tell you more than any isolated episode, and what you really don't want to do is assume that it is a UTI that's causing these problems, and neglect possible other etiologies. I'll give you a quick example. I had a patient with known recurrent UTIs. Her husband would always call when this would happen, and once we got that phone call, and it was her symptom, really worrisome, and while, you know, we're certainly willing to look at her urine, she was told to go to an ED, and she had a subdural hematoma. So, elderly patients have other reasons that they can have mental status changes, and those should not be neglected just because they have a history of UTIs, or because there's a positive urine culture, and that's the first thing that gets picked up on, or a positive UA, it probably would be. So, then the other thing that happens is women who are cognitively impaired and cannot even report symptoms. So, now you're missing, you know, your two pieces of the diagnosis or symptoms and a pathogen, you're missing the symptoms because they cannot tell you, and that is a very difficult situation, especially because if those patients have some kind of history of urosepsis, then their family's going to be especially anxious to, you know, any kind of sign that they give that something is going on. They're going to want to investigate that, and again, it's a difficult situation that's definitely not going to be a black-and-white answer, and it's going to be most well-informed by that relationship with your patient and seeing them over time. And so, the other, you know, the other thing is you're seeing these patients either, maybe you're seeing them primarily for the UTIs, but I think oftentimes we're seeing them because we're also seeing them for another urogynecologic problem, and there's a lot of overlap with those symptoms. A patient with a urinary tract infection may have dysuria, frequency, urgency, suprapubic pain, maybe hematuria, but all those things could be present also in a patient with painful bladder syndrome. In fact, many of you will know that, you know, patients will present with exactly those complaints. Now, I kept thinking I had a UTI, but they keep saying that the test is negative. OAB, you're going to have frequency and urgency, and some people even describe that urgency as discomfort bordering on pain. That's always a little bit, you know, hard. I'm never sure if that is really more in the realm of painful bladder syndrome, but I think that some, that's just how some people experience and describe the urgency, and then we have patients, obviously, who have genitourinary syndrome of menopause, and they can certainly have dysuria and frequency. They may even have microscopic hematuria from atrophy, and they may have bleeding that they're thinking is hematuria because, let's say, they could have bleeding from a urethral prolapse, which is also a result of atrophy, but what those conditions should not have is a positive urine culture. However, we have already talked about the presence of asymptomatic bacteria, which becomes more prevalent in older people, so it's possible that symptoms could coexist and not be causal, so you do have to, again, watch a pattern. When you're evaluating these patients, you know, you have to do everything you normally do, but in your history, try to be very, very explicit about what their symptoms are. It's not unheard of to get a patient who's sent to you because they've had a number of positive urine cultures and have never had symptoms, in which case I say you're fine. People also are very hung up on the odor of the urine. Is it cloudy? I mean, other than gross blood, it doesn't really matter what it looks like. I try to impress upon patients that the odor of the urine is impacted by everything you take in, and so that, and also how much hydration you have is going to amplify whatever that is, so that's not, it's not very helpful. They need to have actual symptoms. You want to go over possible risk factors, and of course, their medical and surgical history, because that may point you toward other parts of the evaluation, and it may mean that there are other coexisting conditions that need to be treated. Patients with poorly controlled diabetes, you know, if their urine glucose is high, that's certainly going to both increase their risk for infections and increase their irritability, so that's something that needs to be addressed by their primary care provider. On their evaluation, you know, I include vital signs. Of course, if you're worried that a patient has pyelonephritis and you need to establish whether or not they're febrile, your general cystitis patient is not going to be febrile. On pelvic exam, there's some specific detailed things that we want to look for and document whether or not there's atrophy and how much is their discharge. Are we thinking this is more of a vaginitis that's causing them whatever symptoms they have rather than a UTI? Are there masses? Is there a urethral diverticulum or some other pathology that is contributing to their infections? Possible foreign bodies, possible mesh, and then of course, if you are suspicious or concerned for pyelonephritis, you want to look for a CVA tenderness. As far as basic testing, I think a UACNS is reasonable. A dipstick is not generally helpful in this population. It's good for patients who have a low suspicion going into it, but it's not particularly helpful. The thing that's helpful in a UA is the microscopy. There's debate about whether or not pyuria is necessary for the diagnosis of a UTI. I tend to feel that if there is a positive culture and symptoms, there may or may not be pyuria. Beyond a standard urine culture, there are centers that are using the expanded quantitative urine culture. This is basically a technique where they're using more urine grown on more types of media under differing conditions, and they're able to detect a lot more pathogens in this. It may be something to consider in those really tough patients where everything that should work isn't working. It's something that you'll have to be finding a lab that does that and send the specimens to them. It's something to think about. It may become something that's more useful in the future. We also talked about culture-independent techniques using RNA sequencing. As far as I know, this is not clinically applicable right now, but it's certainly giving us a lot more information about the urinary microbiome. Hopefully, that will really add a lot to treating these patients and understanding these patients. As additional testing goes, I think it's probably reasonable in most patients to ensure that they're not having retention, although that's pretty rare. Again, if you're seeing patients that are more refractory to treatment, it would be wise to rule out a problem with retention. Cystoscopy and imaging is really not something that has to be done on every patient and I think that's pretty safe to say, but once there's any concern for something that would put them in a different category, they have history of stones, is there a reason to be concerned that they have a foreign body somewhere in their urinary tract, is the pattern of infection, is there something unusual about that pattern, are there really multi-resistant organisms or strange virulent organisms? These are things that might push you to taking a closer look either with cystoscopy or imaging. And again, if a patient is just not responding to normal treatment, then you may want to look for a potential other source. In our world, of course, cystoscopy may be important in patients who have surgery in and around the bladder and urethra. Certainly, foreign bodies are sometimes found and may be a nidus for infection. Cystoscopy is not especially, it doesn't seem to add a lot in general, but it can detect some pathology that's not seen on imaging. But again, the overall rates of detection are low. Luckily, cystoscopy is also, you know, for most patients, relatively benign procedure. It has some risks, of course, but in terms of testing, it's something that can be done with relative ease. Imaging, again, only on select patients. You can think about a few different options. Ultrasound, of course, has the advantage of not having any radiation involved. A non-contrast CT is pretty standard for looking at kidney stones. CT urogram is more sensitive at picking up smaller stones and small masses. And you can see there the different sensitivities and specificities for our CT versus a renal ultrasound. But again, the trade-off is ionizing radiation from the CT scan. With pyelonephritis, you don't have to get a CT in all those patients. I think, I feel like, when I was in medical school, we did. But if they are responding to treatment and there's no suspicion that they have some kind of obstruction, their symptoms are not so severe, you know, that they're vomiting and unable to tolerate PO, febrile, you know, and not responding to antibiotics, then you certainly would want to to look further with the CAT scan. In terms of diagnosis and management, which I think are sometimes part of the same process, so you may not be able to see a patient and know for sure that that is their diagnosis. There may be that you need to review the testing from the last several months that, you know, they've been seen sporadically in this urgent care and then that primary care office and then over here and somewhere else. And you might need to gather some of that information. I generally try to really do some counseling at that point about what, you know, what a UTI is. Again, why it's not because of some moral failing on their part. And then give them some tools to make it more manageable because the other thing that is so bothersome to patients is just having symptoms, not being able to get treatment in a timely fashion, and that becomes really scary. So one thing that we do in our practice is give patients a standing order. So I say call if you have, if you're having UTI symptoms, but you can just leave a message and go straight to the lab to have this order and submit a urine. I do want to know what the symptoms are so that it's not just, oh, my urine smelled funny. I put in a test. It was really, we want to know what they are. Some patients will ask you if they can have a prescription for antibiotics because it's so terrible once the symptoms hit that they cannot wait. I'm okay with that unless they prove to me otherwise that they're going to take that in a way that's not really responsible. But otherwise, I think that's reasonable if they can try to give you that sample before they start. And as I feel like I've made the point that following these patients over time is really key. So treatment Antimicrobials are certainly the mainstay of treatment. What we know is basically extrapolated from the data on episodic UTIs. So whether or not the time courses that we usually use these antibiotics for and the dosing is effective in your recurrent UTI patients may not be the case and you may have to go outside of those norms, but it's certainly a reasonable place to start. Recurrent UTI without complicating factors, these three antibiotics are what's recommended currently in the U.S. That's not the case necessarily across the world, but that's what we have. I know where I practice, Fosamicin is rarely covered so that though it is considered a first-line agent, it is a fight to get patients to actually take it. Now, patients who have complicating factors, immunosuppression, chronic catheterization, significant abnormalities of the GU tract I'm not talking about. They have a history of a sling and there's nothing in their bladder, but like a congenital anomaly, something like that. These are not the same people, right? So they should be able to afford that. That kind of thing is going to be more appropriate. So this is from that best practice, best practice statement. And so it's just a summary of what we're looking at. So we're looking at the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. and the U.S. Other things to consider is, of course, hopefully, you're going to have the sensitivities at some point for these patients. Patients may not be willing to wait for the sensitivities because they're in so much discomfort. Nonetheless, you can follow up on those and tailor the treatment appropriately. Allergies, of course, come into effect and may be something that's very limiting for treatment of some patients and may even drive you to have them tested because it's so limiting. Medication interactions you want to think about. Certain commonly used antibiotics will interact with warfarin. And then renal function is important, especially for nitrofurantoin. Since it's a first-line agent, it's important to note that estimated GFR of greater than 30 milliliters per minute is the cutoff. These patients, if they don't have appropriate renal function, they're not going to get benefit from nitrofurantoin. A while ago, that cutoff was 60 milliliters per minute, but the powers that be had realized that that was really limiting a lot of patients, especially our older patients. As far as non-antibiotic treatment, there have been studies of other things. Using ibuprofen alone has been studied in UTIs, but not studied specifically in recurrent UTIs. In the studies of patients with episodic UTIs, there was some slight but increased risk of developing pyelonephritis. This kind of is just speaking to the idea that it's an infection like any other that the body can potentially clear, and what you're really treating is the symptoms. Again, not necessarily established in recurrent UTI patients. Chinese herbal medicine refers to several different herbal combinations, and there has been a Cochrane review looking at not a lot of studies, seven studies, and they did see that there might be some benefit. These patients did respond and even found a reduction of recurrent UTIs for up to six months, but they weren't able to really be conclusive because of the limited data. Things that are kind of unusual but may be something to consider again in those very difficult to treat patients are intravesical treatments. We'll talk a little bit about gentamicin when we talk about prevention, but it has been used in treatment, usually in neurogenic bladder patients, so that is a different population, but again, we're talking about when you're at your last at the end of what you know to do with these patients, you may start to have to be a little more creative. It does seem that the adverse events are very, very low, so that's one nice thing about that. Colistin is something else that can be instilled into the bladder. It has kind of a deleterious effect on the lipopolysaccharide components of a gram-negative organism, so that's how they kill the bacteria. There's literally just case reports in patients who are critically ill, have some kind of multi- resistant acinetobacter, so this is again not widely applicable, but you may get in a situation where you're really in that small percentage of patients. Let's talk about prevention. Prevention. Behavioral stuff is the thing that everyone is going to talk to you about. Oh, I do that. I make sure I go to the bathroom before and after I have sex. I'm trying to do all this stuff, and there's really no data to support these measures. Some say, well, simple enough. They can try those things. I think that maybe yes, maybe no. Some women really drive themselves crazy trying to do all these things to limit their risk for UTI when we'd have no idea if it will or won't. The things that we do know about are antibiotic prophylaxis that has been proven to decrease the rate of recurrence and vaginal estrogen, so those are really our opportunities for intervening for prevention. In terms of prevention, there's many regimens and they're listed here in this chart that you can try, and there is some differences in terms of the UTI rate, but I would generally say it'll probably depend more on their pattern of pathogen and what you can use for them as well as their allergies and their other medications, so that's probably going to tell you what they can use. Trying to illustrate what changes happen to the vaginal epithelium when in menopause. The idea is that there's a loss of that of the glycogen that allows lactobacillus to really thrive and that's what allows for other bacteria to become more prominent and therefore more available to become pathogenic to the urinary tract. I've heard people describe it as a probiotic for the vagina. Estrogen prescription is not without its challenges. A lot of patients remain fearful, but it has been shown to be one of the only things that can prevent UTI. You can assure your patients of that. You can also talk to them about the fact that in the studies that have been done, there's quite a good amount of data about these things. There does not seem to be the same risk as oral estrogen. And oral estrogen, on the other hand, will not have this beneficial effect for recurring UTIs. They wouldn't want to do that. Try to convince your patients to use estrogen. The challenging scenarios are those patients who have allergies to multiple antibiotics, cultures that come back with a multi-resistant organism, those patients who cannot tell you what their symptoms are, and then, of course, there are patients with all those issues and more. We'll take the case of one such patient that you may find familiar. Joan is a 66-year-old woman with recurrent UTIs. She reports allergies to sulfapenicillin and fluoroquinolones. She is already using vaginal estrogen twice a week for the last six months, but has had five UTIs during that time. With each episode, she had a urine culture, and that showed E. coli, which was not multi-resistant, resistant only to ampicillin, so that's good news. So, she's been treated with both nitrofurantoin and fosfamycin, and symptoms resolved, but recurred within a few weeks. So, what do we do with Joan? So, if she hasn't had any of the testing, it might be reasonable to do that. If we want to expand our available agents, we might want to see about an allergist because some patients have allergies listed that they don't even remember why or what happened, and may not be correct, and so it's reasonable to look into that, although it certainly does take some effort on their part. And if we're going to go down the road of giving this patient prophylaxis, what options do we have? She already has so few things that she can use. So, one thing that I think is useful is methenamine. So, methenamine is related to ammonia and formaldehyde in the acidified urine. I don't really describe it that way to my patients because I feel like that would be scary. What I just tell them is it creates chemical reaction that makes it very hard for the bacteria to grow. It does not seem to create resistance, which is excellent. It does not seem to have a lot of adverse events. You do have to be careful in patients with renal or hepatic disease. But it was, they did conclude in a Cochrane review a few years ago that it can be helpful for preventing UTIs. Probiotics is something that I think everyone would like to think this would work. It makes sense, but there haven't really been enough studies. They're all sort of using different formulations, different administrations, and so we haven't gotten to that point. The Cochrane review showed that it did not reduce recurrent UTIs. But again, it may just be a question of figuring out what the ideal formulation is. A lot of patients will tell you this, as soon as I think I'm having UTI, drink the cranberry juice. That is not going to help them at that point. But could it help them prevent a UTI? I would say the jury is still out, although the Cochrane basically did not find that it reduced symptomatic UTI. There have been a few studies since then that have found some benefits. The 2016 study that was widely publicized, JAMA of women in nursing homes did not find, in fact, but they were not actually looking for UTIs. They were looking for pyuria and bacteria. I think, again, the issue with cranberry, so the reason that it's thought to be helpful are these chemicals, the proanthocyanidins that inhibit a certain fimbria of uropathogenic E. coli. I think again, we have the issue of regulating dosing and delivery, and so that may be what's at issue here. I think it's reasonable and okay for patients to try, but they don't need to spend a lot of money on cranberry supplements if it doesn't seem to be getting them anywhere. One thing that I do think is promising is D-mannose. D-mannose is a simple sugar that competitively inhibits the type 1 fimbria of the uropathogenic E. coli, and there's been one RCT where it was actually even more effective than a daily dose of 50 mg of nitrofurantorin, and so again, I think that this is something that would go under the heading of not completely proven, but likely to be helpful. Other installations, so this is again definitely in the realm of not standard, but something to think about. Again, gentamicin and neomycin installations have been studied and reported, mostly in patients with neurogenic bladder and are usually given daily. A lot of these patients are catheterizing, so they can give themselves daily installations. They're not incontinent. They're usually more not urinating, so they can have it dwell for as long as overnight. So this is a little bit harder to, I've considered this in patients, and it's hard to operationalize if patients can't instill it themselves. How are they going to come and get this every day? But it's something that I think probably has promise. Hyaluronic acid and chondroitin sulfate installations, the idea there is that could there be repair of the glycosaminoglycan layer? Again, very limited data. All right, we're running out of time. I want to answer some questions. So the last thing I'll mention is vaccines. So this is something that is definitely not standard, although is available in other countries, and I think is very promising. We just need more data. So there has been a systematic review of this formulation OM-89, which is also, I believe, called the Urovaxome. And that is a formulation of several non-live uropathogenic E. coli given orally versus Urovax, which is a vaginal suppository of several serotypes of various bacteria, not only E. coli. And that seems to be a little bit more efficacious. So this data is from a little about five years ago, whereas there was a review in 2017 that looked a little bit more closely at three different immunostimulant preparations. And this is just basically showing if you look, maybe this is more helpful. If you look at the right side, you're just seeing the reduction in the number of UTIs. But unfortunately, again, the quality of evidence is not quite there just because of the quantity of studies. But that's something that I would say to look out for as something that could be helpful. So just to quickly summarize, ensure that these patients are having symptoms and find out what those symptoms are. You do need to do some testing to get a culture, track what these UTIs are. But maybe that may be all the testing. Please help your patients to stop obsessively cleaning and doing things that are probably actually harmful. Treat their acute episodes appropriately and their exacerbating comorbidities. The things that we can actually do for prevention, do them, especially vaginal estrogen, and then some other preventive measures that may be helpful. And as not every patient is going to be appropriate for antibiotic prophylaxis, but definitely have that discussion with them that that may be a possibility and it may come to that. And watch out for developments. Hopefully, we'll know more about the urinary microbiome and more about potential vaccines and things that will have a longer lasting effect and not put us in the position of using so many antibiotics, which of course is a problem at a larger level. So, I'll answer some questions. Thank you, Dr. Carberry, for your presentation. We actually do have a few questions. And remember, you can submit your questions for Dr. Carberry in the question box on the left-hand side of the window. So, Dr. Carberry, we have a question. Can a patient get a clean catch with a sterile cup and store it in the refrigerator overnight? Should. And I would say the patient should talk to the lab that they are using. Not every lab will allow that. I think some might. It's probably best not to take the chance to get it to the lab as soon as you get the specimen. But I know, of course, that's not always possible. But there is definitely patients who did that, and then the lab said we can't accept that. So, it'd be important for them to try to maybe establish that ahead of time. Our next question. For a patient with recurrent UTIs, unremarkable medical surgical history that's unresponsive to treatment, what's your go-to imaging modality? X-ray, ultrasound, CT, with and without contrast? Great question. So, I think that there's no right answer based on the data that we have. I usually would start with a renal ultrasound because of the, you know, just to minimize the risk of radiation. Admittedly, that is going to miss some very small lesions. But then again, you wonder about the clinical significance of those lesions. And then, you know, I would consider cystoscopy if that seems like there could be a potential contributor there. We have another question. Is there any place for using Cipro for first-line treatment of UTIs? So, for patients with uncomplicated UTIs, that I would say no, except for if they have legitimate allergies to everything else, then, yeah, then you could, I mean, again, I really try to steer clear of it, but you know, let's say they're allergic to Bactrim and Nitroferantoin and Phosphamycin or they can't get Phosphamycin. I've definitely had that situation. Yeah, you could use Cipro. But I would say try your best to limit that. How do you guys use, you know, dose the D-Manos and the Methanamine? And then I'm going to just kind of add to that question. We generally, in our practice at Northwestern, when we have someone on Methanamine, we have them do 1 gram BID in conjunction with BID vitamin C. Is there any role for that? Yes, absolutely. So, the Methanamine is ideally supposed to be used to work in acidified urine. Anecdotally, I'll say, I think without that, vitamin C alone has been looked at, and it doesn't seem to work on its own, but the combination, I think, is right, and we use the same dosing. I usually use Methanamine Hippurate. There's another formulation, but the Methanamine Hippurate is 1 gram twice a day. How about the D-Manos, Dr. Carberry? How do you dose that? I think it's 2 grams daily. I would have to look up, because that's not a prescription. That's something that patients can buy over the counter at, you know, probably Whole Foods or a nutrition supplement store, and it should be, and there are actually formulations that are like for, you know, for bladder health, Cranberry and D-Manos, things like that, so that's usually included. We have a few more minutes left. Do you use molecular PCR testing for negative cultures in someone who is symptomatic? I have not had the ability to. I don't know how we would order that, but it's certainly an interesting idea, because you will definitely get those patients. I think a lot of those patients end up getting put in the painful bladder category, but who knows if that's really legitimate. I think the question is, it depends on kind of like what the data is that you get from the PCR testing, but that's a long answer to your question, but no, I have not done that, but it's something to think about. Okay, let's do one more question. One of our listeners writes that they've heard that some pharmacists say that fluoroquinolone dosing for a patient with chronic kidney disease needs to be adjusted based on the estimated GFR, but others say it doesn't because of the short time frame of treatment. Do you typically check GFRs? That's a great question. I don't always check a GFR, but I do look for one in the chart, and a lot of times patients will have one that they had drawn by their primary care provider recently. I think for a short time course it may be less important, but you may find that the effectiveness is impacted, and so you're not going to get the benefit that you thought you were. Well, that would be definitely true for nitrofuranto and for fluoroquinolone. I think it would be best to renally dose it. I don't see why you wouldn't. I guess the only thing is you couldn't if you didn't have their estimated GFR, but if they're a patient with chronic kidney disease, that's probably being monitored, so I think you would be able to get that. Well, on behalf of the Oggs Education Committee, I'd like to thank you, Dr. Carberry, and everyone for joining us today. Our next webinar is titled Pelvic PT, What Really Happens Down There?, and will be presented by Cindy Fury on May 8th. Thanks again, Dr. Carberry. It was a pleasure to have you, and thanks to all of our listeners. Yes, thank you.
Video Summary
Dr. Cassandra Carberry, an assistant professor and clinical educator in the Department of OB-GYN at Brown University, was the guest speaker in a webinar about the management of recurrent urinary tract infections (UTIs) in non-pregnant women. Recurrent UTIs are defined as two culture-proven infections in six months or three in a year. Dr. Carberry discussed the challenges of diagnosing UTIs in these patients, especially when symptoms may be vague or when patients are cognitively impaired and unable to report symptoms. She explained that the most common pathogens in recurrent UTIs are from neighboring organs like the vagina and rectum, and that uropathogenic E. coli is the most common pathogen, with non-E. coli pathogens being more common in recurrent UTIs compared to episodic UTIs. <br /><br />Dr. Carberry emphasized the importance of a thorough history and physical examination to rule out other conditions that may present with similar symptoms, as well as to identify any modifiable risk factors. She also discussed the various diagnostic and imaging tests that can be helpful in identifying underlying causes and complications. Treatment options include antimicrobials and non-antibiotic approaches such as ibuprofen, Chinese herbal medicine, and intravesical treatments. <br /><br />Dr. Carberry highlighted the use of vaginal estrogen as a preventive measure, as well as the potential benefits of methenamine and D-mannose. She also mentioned the possibility of vaccines for UTIs in the future. Dr. Carberry concluded by recommending a personalized approach to managing recurrent UTIs, considering the individual patient's history, symptoms, risk factors, and response to treatment.
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Presented by: Cassandra L. Carberry, MD, MS
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Date: April 10, 2019
Meta Tag
Category
Education
Category
Pelvic Pain
Keywords
recurrent urinary tract infections
non-pregnant women
diagnosing UTIs
common pathogens
history and physical examination
treatment options
vaginal estrogen
methenamine
personalized approach
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