Narrator - Dr. Abel 0:00 Welcome to HelixTalk, an educational podcast for healthcare students and providers, covering real life clinical pearls, professional pharmacy topics and drug therapy discussions. Narrator - ? 0:11 This podcast is provided by pharmacists and faculty members at Rosalind Franklin University, College of Pharmacy. Narrator - Dr. Abel 0:17 This podcast contains general information for educational purposes only. This is not professional advice, and should not be used in lieu of obtaining advice from a qualified health care provider. Narrator - ? 0:27 And now on to the show. Dr. Sean Kane 0:31 Welcome to HelixTalk episode 195 I'm your co host, Dr. Kane, and I'm Dr. Patel, and the title of today's episode is burning questions about uncomplicated UTI diagnosis and treatment. Dr. Khyati Patel 0:43 Well, Dr. Kane, it's been a minute since I thought about the last IDSA guideline update. So what is what is new here? Dr. Sean Kane 0:51 So not to call IDSA out, but a little bit of calling out their last guideline update on uncomplicated cystitis was back in 2010 so that means that it's now a 16 year old guideline. Funny enough, though, if you go to their website, it says, quote, this guideline is currently in development. And being the kind of nerd that I am, I went to the Wayback Machine, which is it like a website where you can see the archive of a website over time at different years. So back in 2019 it said it was being updated with a projected Publication Date of summer 2022 so I don't know when the guidelines will be updated, or if they will be updated, but clearly the IDSA guidelines are a little bit behind the times at this point and are in need of an update. Dr. Khyati Patel 1:33 So it seems like we have some new evidence, new guidelines, and therefore we are here to review that clinical presentation of UTI, diagnosis and treatment. So what are some of those new resources we're relying on? Dr. Kane, yeah, so Dr. Sean Kane 1:45 you'll see it in the show notes. There's two, one that is from 2024 from the American family physician. And kind of as a pro tip, this is a resource or a journal that I kind of haven't read that much, except for maybe the last couple months, and I've been really interested in some of the review articles that they have. What I really like about these review articles is they're really high yield, simple and really focused on, like the primary care provider, as opposed to the specialist. So if you want to know about cholesterol management or heart failure or whatever, as a simpler review than a hundreds of page review document from the ACCA Ha, this is a really good resource, especially for students that just want like the Cliff Notes version and the like less high level expertise and more like the normal clinician view. I was really surprised with the quality of some of these review articles, including the one for uncomplicated UTI that is in our show notes. Dr. Khyati Patel 2:38 And I like the organization, it seems like a very condensed summary that's visually appealing, and you can find the information you need, kind of like a guidelines at glance, type of an overview Dr. Sean Kane 2:49 for sure. And then the other one, which Dr. Brazil, don't laugh, was 2024 wiki guidelines sounds like Wikipedia. It sounds like Wikipedia, or WikiLeaks or something like that. And I promise you, this is way more reputable than what it sounds like, and I was pleasantly surprised. And we're going to dive into these new 2024 UTI guidelines from wiki guidelines. Dr. Khyati Patel 3:13 All right. Well, I want to learn more about it, but let's kind of set the stage of like, why we're talking about it. You mentioned that IDSA guidelines have not changed in the last 15 years, but then what has changed? Why are we talking about UTIs today? Dr. Sean Kane 3:26 Yeah, so unsurprisingly, bacterial resistance rates for a variety of antibiotics that we commonly used 15 years ago, those resistance rates have changed. So for example, back in the day, amoxicillin and ampicillin were sometimes used for uncomplicated UTIs, but in modern era, the resistance rates are about 55% so effectively, it's a coin flip whether the bacteria you're treating is empirically resistant or sensitive. Bactrim (sulfamethoxazole-trimethoprim) resistance rate is at least 20% but it depends on where you live, and then fluoroquinolones, this used to be like 99% sensitivity, or 1% resistance rates. It's now somewhat higher in terms of like 10 to 20% resistance rates. And on top of that, since 2010 we've seen a host of FDA warnings about the fluoroquinolones drug class, Dr. Khyati Patel 4:16 yeah, and I think they include things like tendon rupture, peripheral neuropathy, aortic aneurysm, CNS changes and stuff. So we try not to use them for frequent, recurrent kind of use. Dr. Sean Kane 4:29 Anyways, yeah. And then the last kind of interesting update is that a new drug was approved by the FDA in 2024 for uncomplicated UTIs in women. We'll jump into which drug that is and kind of what the evidence was for that as well. Dr. Khyati Patel 4:42 So, Dr. Kane, we talked about the wiki guidelines. I'm actually, before you even go deeper into the UTI stuff, I'm intrigued and knowing what they are, and how does this group come together and write guidelines? Dr. Sean Kane 4:53 Yeah. And Dr. Patel, for full disclosure, this is something that was kind of new to me as I was reading about uncomplicated UTIs and. I came across that guideline article, and then it kind of led me down the rabbit hole. So wiki guidelines is an organization with basically a really unique approach to guideline development, so their focus is basically just high quality evidence with minimizing expert opinion. And this is actually kind of a dig at the IDSA guidelines, there was a way back in 2010 so it's outdated, but there was an article published that looked at what percent of IDSA guidelines are expert opinion and quality. And you know, most guidelines shouldn't have that much expert opinion, because the whole point of a guideline is that you're taking evidence and then synthesizing the evidence into a evidence based recommendation, but that 2010 publication showed that 50% of IDSA recommendations are expert opinion only where they're making recommendations with no data to support it, which is a problem, and that is one of the tenants of the wiki guidelines approach. The irony, though, is that for this particular topic, there's just not a lot of superiority data to say you should do X versus Y for uncomplicated UTI. So even though the guidelines prefer to not have expert opinion, they ended up kind of having more expert opinion than probably they wanted, just because that's what the data is for uncomplicated UTI. Dr. Khyati Patel 6:17 So it sounds like it's a group that's not affiliated with IDSA who get to be an author. Dr. Sean Kane 6:24 So I can tell you can be an author if you want. So basically, anyone can be an author. And the way that they find their authors is that they crowd source it through social media. So they say, Hey, we're going to write a complicated UTI guideline who wants to be involved. And it isn't necessarily restricted to infectious disease, although the current guidelines from wiki guidelines are ID related, but it could be any topic, specialty or disease. Dr. Khyati Patel 6:47 And it seems like these are not just for, you know, academic medical center or kind of sub specialists. It's kind of intended more for the generalists, exactly. Dr. Sean Kane 6:56 So these are intended to be guidelines that are easy for people to understand who aren't Uber experts in the field, kind of like the American family physician journal articles, where it's really intended to be kind of the general approach to the disease state, not the Uber specific subspecialty approach to that disease state. Dr. Khyati Patel 7:13 And then the word wiki guidelines. So am I just gonna go and, you know, Google wiki guidelines, and I'm gonna find it. It's kind of like a Wikipedia page, sketchy looking, kind Dr. Sean Kane 7:23 of so you'll find them in PubMed. So their guidelines are peer reviewed, published and peer reviewed journals. They do have a website. They currently have osteomyelitis, endocarditis, and then UTI guidelines. And just for the UTI guidelines, which are referenced in our show notes, these are published in JAMA Network, open, which is Jama. So this is, like, a well known journal. It's not like a journal you've never heard of that they happen to be published in. It's a really big deal that they got published in a peer reviewed journal. Dr. Khyati Patel 7:51 And I was kind of intrigued, so I looked into it, and there's like, what, 50 authors? Dr. Kane, yeah, yeah. And you also pointed out that the first author was a pharmacist, and so I hit the down button to see how many more there were. There's 23 pharmacists. So hey, there is an opportunity. Yeah, half of the guideline is made by pharmacists, and that's actually a really good example of professional contributions. But I would say that as I was going through the names, because I had to know if I know somebody right. Guess who I see? Our very first graduating class alumna, Dr. Alyssa Christensen. She is actually one of the authors Dr. Sean Kane 8:28 that is so cool and way to represent RFU in a really neat way. Dr. Khyati Patel 8:32 Yeah, so. Dr. Christensen, if you're listening, huge shout out to you. Thank you, and you make us proud. Dr. Sean Kane 8:39 Love that. Well, why don't we dive into the actual articles, right? So wiki guideline article, and also the American family physician article, kind of giving a broad overview. So Dr. tell the first thing we have to talk about is what exactly is an uncomplicated UTI, as opposed to a complicated UTI? So another term for this is acute, simple cystitis. But what are the actual criteria that we're looking at? Dr. Khyati Patel 9:04 So uncomplicated kind of think about lower urinary tract, right? So bladder, so it's not infection of the kidney, which is where we call it the upper UTI or pyelonephritis. So we're not talking about the systemic symptoms like fever, malaise, you know, flank pain that can come or cost of vertebral angle tenderness and things like that. You're just talking about like bladder specific symptoms, Dr. Sean Kane 9:33 and then no signs of systemic illness, so no fever, malaise, chills, tachycardia, nausea, vomiting, basically, you're just having the lower urinary tract symptoms, you're not immunocompromised, you're not pregnant, and you don't have any abnormalities with your urinary anatomy, like a surgery or something like Dr. Khyati Patel 9:51 that, and also not associated with the catheter if somebody is wearing your urinary catheter. Dr. Sean Kane 9:57 So then obviously, our symptoms, if we're. Excluding all of those, what are some of the symptoms that a patient would Dr. Khyati Patel 10:02 have right more frequently? It's the urgency. So urinary urgency increased urinary frequency or even bacteria, so wanting to go to the bathroom overnight, some patients may complain of burning or dysuria when they're urinating, some tenderness and pain in the suprapubic region. And then one thing to keep in mind, we talk about this as a, you know, specific population, but our older patients may have some atypical symptoms. So what I just described were like kind of the classic UTI symptoms in most people, but our older patients may experience things such as confusion, delirium, dizziness, lethargy and loss of appetite. So kind of keep you know those things in mind too. Dr. Sean Kane 10:46 Then in terms of the typical patient that we'll see with an uncomplicated UTI, 80% of the time is going to be women, and usually it's women between 18 and 29 years of age. It's extremely uncommon in men less than 60. And then once you get to about 80 years or older, the incidence rate between men and women is fairly similar between the two. Dr. Khyati Patel 11:07 So the common pathogens that we are dealing with in the uncomplicated UTI for the most part, is, is geracia coli, right? E coli? We're talking like 75 to 90% of the UTI cases belong to this pathogen. Dr. Sean Kane 11:22 And this is like something that I think bears repeating, Dr. Patel, because when you have a UTI like E coli, literally is almost 90% of the time the pathogen that you're trying to cover. So obviously your antibiotics that you're picking absolutely should cover E coli, and there are other pathogens that you can see, but it's literally a minority of the time that you're going to see strep in the urine, or Klebsiella in the urine, or Proteus, you can see those other pathogens, but E coli makes up the bulk of all of the pathogens for UTIs, yeah. Dr. Khyati Patel 11:52 And then again, some of those you mentioned in the gram positive side, Enterococcus or group B strep can also be found, but again, very, very rare. Dr. Sean Kane 12:01 So then diagnosis. How do we know that someone has a UTI? Dr. Khyati Patel 12:06 There is no specific criteria as far as the diagnosis is concerned. So we have to look at the clinical symptoms. So if you, for example, are getting a urine analysis done and something's off by itself, should not count it as UTI, patients should have positive UA, we call it, plus the symptoms that we talked about. Dr. Sean Kane 12:27 And what's really important is that, although there are and we'll go through these certain signs associated with UTI, so for example, leukocytosterase or having white cells in your urine, those are consistent with having UTI, but no guideline to date has said you must have X, Y and Z on your urinalysis for UTI. But what we do say is that the patient should have symptoms and they should have findings in general, consistent with the UTI on the urinalysis, Dr. Khyati Patel 12:54 right, because if they have positive UA, but they don't have symptoms, patients are called to have asymptomatic bacteria. So yes, we are finding the presence of, you know, bacteria, but they don't have symptoms, basically. And the Dr. Sean Kane 13:10 most important thing is that that's not a UTI, so they don't have an infection, meaning we don't treat them unless they're pregnant. Remember, pregnancy was one of our exclusions to be an uncomplicated UTI, but especially in older patients, this is super common that people will see a positive UA and feel obligated to treat and the patient has zero symptoms. You don't treat the patient with zero symptoms unless they're pregnant. Dr. Khyati Patel 13:33 And in one of the documents that we are putting in the show note, Dr. Kane, I was reading and it said that back in the day there was 50% of the time antibiotics were prescribed for asymptomatic bacteria, and then after education and stuff, they brought down the amount to 33% so education and antibiotic stewardship definitely helps. Dr. Sean Kane 13:58 And just remember too like giving antibiotics is bad for two reasons. One, you're promoting resistance, but two, there are side effects of all of the antibiotics. Like, if you told the patient you feel great right now and you have no symptoms of UTI, if I give you an antibiotic, you might have diarrhea for the next three days. Which one would you pick, right so, like, if you start including the patients in that decision making process, acknowledging that diarrhea is really common with many antibiotics, probably the risks and benefits don't make any sense at that point. Dr. Khyati Patel 14:27 I totally agree. So that's clinical symptoms we talked about earlier. What are we looking at? The urine analysis in particular that would show positive signs for UTI. Dr. Sean Kane 14:38 So one thing we're looking at is, are there white blood cells in the urine? And we call this pyuria, or leukocytes in the urine, and they should definitely be present. So like if, assuming you have a normal immune system and you have bacteria in your urine that's causing infection, as part of that natural response, you should have white blood cells in your urine. So usually the threshold is around 10 cells per. High powered field, but it depends. It could be as low as five. So there isn't a specific threshold, but it definitely shouldn't be zero. If you have zero white blood cells, then it's probably not UTI. Dr. Khyati Patel 15:10 And then we can also see positive nitrites. So nitrates are normally present in human urine, but if there are bacteria that can convert nitrates to nitrite and we find nitrites in the urine, then we can also assume that there is bacteria in the urine too. But not all bacteria do that, so that's something to keep in mind, too. Yeah. Dr. Sean Kane 15:32 So that's a great example where if you happen to see nitrites, it supports the UTI diagnosis, but if it's negative, it doesn't necessarily mean anything, because it could be a bacteria that just doesn't do that process. Another finding would be hematuria, so red blood cells in the urine, keeping in mind that other things cause red blood cells in the urine, like a kidney stone, for example. So it's one of those things that if you happen to see red blood cells, that is an abnormal finding, but doesn't necessarily definitely mean that they have a UTI. Yep. Dr. Khyati Patel 16:00 And then we're going to also find leukocyte asteroids, which is an enzyme when white blood cells are kind of fighting the infection itself. Dr. Sean Kane 16:09 Then ideally we would like to see no epithelial cells, which means contamination of the urine sample. So there are things like a clean catch midstream, where you're trying to collect the urine after voiding has started, but not at the very beginning, to help avoid that contamination. But if it's heavily contaminated, you're probably getting skin flora and kind of genital skin Flora as part of that sample, which can contaminate your ability to ascertain whether they have a UTI or not. Dr. Khyati Patel 16:35 So then from urine analysis, we move on to doing urine culture right depends. Dr. Sean Kane 16:41 So there's something called a reflex, which means that if the urinalysis doesn't support a UTI type diagnosis, then the lab won't do a urine culture, but if it does, then the lab can automatically do the urine culture for you, and that's called a reflex, where there are criteria the lab follows to decide whether it should be sent off for culture or not, Dr. Khyati Patel 17:00 and some of the guidelines do recommend actually doing a culture, especially in men patient population. And of course, if you have clinical suspicion for treatment failure, maybe the diagnosis is not clear, maybe the patient is having a recurrent UTI, those are all situations where culture might be done. Dr. Sean Kane 17:20 What's interesting, Dr. Patel, and this is something that I didn't fully appreciate, is among healthy, non pregnant women, the guideline is actually that you don't need to do a urine culture. And I think especially with my hospital background, we cultured everything that moved right. And on the outpatient side, the argument is that if it doesn't dramatically change your empiric therapy, and most patients will actually get better regardless of what you give them. Is it kind of worth the effort and the time to do the culture if most patients will get better, and your empiric therapy usually covers it, right? Dr. Khyati Patel 17:52 So if we are doing a culture, then there are some colony forming unit thresholds that we keep in mind generally. That is, you know, 10 to the five. But I think the newer recommendation is to consider even lower thresholds. Dr. Sean Kane 18:07 And part of it is It depends on the bacteria. So for E coli as an example, given that we know E coli is such a common urinary pathogen, you don't need that much E coli to say, Yeah, that's probably what's going on. So some experts say the threshold would be 10 to the third, but other guidelines might say 10 to the third, 10 to the fourth, historically, is 10 to the fifth. So you needed more bacteria, but it kind of depends Dr. Khyati Patel 18:29 and what happens if there is mixed Flora present. Dr. Sean Kane 18:33 So mixed Flora means that you have a bunch of different pathogens in the urine, which sounds really, really bad, but it actually usually means that you have a contaminated urine sample. It isn't that you can't have a poly microbial UTI, but it's really uncommon. So more common if you see multiple different kinds of bacteria, you probably got a lot of skin flora in your urine sample, as opposed to the actual pathogen that is in the urine, right? Dr. Khyati Patel 18:56 So kind of going back to the technique on how we collect the urine sample, doing the clean catch, you know, midstream, all that stuff is important. Dr. Sean Kane 19:04 So then treatment wise, moving on to treatment. What's interesting is that no matter what you do, most people who have uncomplicated UTIs will improve, even if you don't give them antibiotics, and we still give them antibiotics. But I think that just highlights the fact that your empiric therapy doesn't matter as much as you might think, Dr. Khyati Patel 19:21 you're also saying that the UTIs will improve if you prescribe the antibiotic and the bacteria is resistant to it, yeah? Like, because the cultures take a little bit longer, right? Sensitivity and culture take a little bit longer, yeah. Dr. Sean Kane 19:34 And I remember, even when I was a PGY one resident, one of my jobs in the ER was to call patients after they went to the ER with the UTI, and tell them, hey, the Cipro that you got for your UTI is that the bacteria is actually resistant. You make that phone call and, like, literally, probably seven out of 10 times they say, I'm feeling looking great, like I don't need to change my antibiotic because my UTI symptoms have resolved. Even though the lab said that the Cipro shouldn't work, it. Did work, and there's a variety of reasons why it may have worked. Or the body, if they have a normal immune system, they can fight it off themselves. In that case, you probably shouldn't give them a new antibiotic if, basically, their infection has resolved. Dr. Khyati Patel 20:11 So then what is really that place of therapy of antibiotics? Are we trying to reduce its progression to maybe upper UTI like pyelonephritis, Dr. Sean Kane 20:19 for sure? And if you talk to a patient who has symptoms like they want to take something for their UTI symptoms, right? So it makes sense that we should help them feel better, and maybe antibiotics help patients feel better sooner than they otherwise would, but you're absolutely right, like, we don't want other complications like that, E coli traveling up the ureters, up to the kidney and causing pyelonephritis. Even though that risk is low, it's still worth making sure that that doesn't happen. Dr. Khyati Patel 20:44 Progression to pylo without antibiotic will occur in one point 43% of the cases. But with antibiotic, it would be point 46% of the cases. So we're looking at what 100 patients to treat. Dr. Sean Kane 20:58 Yeah, so number needed to treat of 100 or a 1% difference, given that the baseline risk is less than 2% like, it's uncommon that's going to happen, but still, like, especially for symptomatic management, it seems reasonable to treat Dr. Khyati Patel 21:11 and so you highlighted Dr. Kane that let's just go with the empiric, right? Let's not wait for the culture and the sensitivity most of the time, and uncomplicated UTI, we're gonna do empiric therapy. What are some of the first line antibiotics that we would Dr. Sean Kane 21:25 go for? So the number one that I think everyone should ingrain in their brain is kind of the typically preferred therapy in most patients, is gonna be nitrofurantoin or Macrobid. This is given 100 milligrams twice a day for five days. In women, if you look at the package insert, it says that you have to have a a creatinine clearance of at least 60 for the drug to work effectively. There is other data in the guidelines also references that for short term use, so not for preventative for short term use of that five day duration, even if your creatinine clearance is between 30 and 60, it's probably okay to still use but that's not consistent with the FDA packaging, but we do have evidence for that 30 to 60 patient group. Dr. Khyati Patel 22:04 Yeah, limited evidence. But like you said, if it's going to be the prophylactic, long term therapy, then we want to make sure that that their creatinine clearance is good so the drug can concentrate and work like it's supposed to in the bladder, again, continuing this discussion on empiric therapy for women, the other agent we have is fosfomycin. This is a one dose treatment type of a case. So a patient would get, like, a three gram oral powder. They'll mix with the water and take it. Phosphomycin is technically reserved for, like, the multi drug resistant pathogens, so not going to be your like first go to therapy. Dr. Sean Kane 22:41 The other problem is that labs don't routinely test for sensitivity of fosfomycin, so you actually don't know for sure that the E coli you're treating is fosfomycin sensitive or not. It probably is, but it would be nice to have that, but again, like probably better to reserve this for the more resistant pathogens if we can. And then Dr. Khyati Patel 23:00 earlier, Dr. Kane, you said that you know bactrims resistance rate are increasing. 20% of the cases you know are resistant to the Bactrim. But Bactrim DS, which is double strength, so sulfamethoxazole, trimethoprim, 800 slash, 160 milligram, twice daily for three days, can be used, or in some cases, just try methoprim 200 milligrams twice daily for three days, can work. Dr. Sean Kane 23:26 And the big thing here is that it depends on your geography. So there are some places where Bactrim resistance rates exceed 20% and the recommendation is to not use Bactrim as empiric therapy. But in other areas, if it isn't 20% so less likely to be resistant, then Bactrim could be a reasonable option for that three day course. Dr. Khyati Patel 23:46 And then we have actually the new agent that we were referring to earlier that was approved in 2024 and that is pivmecillinam. Brand name is Pivya, 185 milligrams three times a day for three days. Dr. Sean Kane 24:00 This was FDA approved back in 2024 so it's fairly new. It isn't extensively mentioned, definitely not in the IDSA guidelines. And it is kind of mentioned because it has seen international use before its FDA approval. Dr. Khyati Patel 24:12 So that kind of summarizes our agents that we empirically use if a patient is women who has uncomplicated UTI. So we got nitrofurantoin, fosfomycin, again, saved for that MDR pathogens, depending on the resistant data, you could use Bactrim or just trimethoprim alone. And then the Pivya, which is the newest drug, pivmecillinam. Dr. Sean Kane 24:37 And then for men with uncomplicated UTI, again, this is really uncommon in younger men. Our go to is going to be typically nitrofurantoin or Macrobid. Again, Bactrim could be used and then trimethoprim alone could be used. Again, there are concerns about trimethoprim and Bactrim resistance, so kind of the again, the number one best option is probably going to be nitrofurantoin. The big difference, though, is that a. Your duration of therapy is going to be five to seven days for men versus when we treated women, it was a five day duration for nitrofurantoin and then just three days when it was used with Bactrim. So longer duration up to seven days. And the guidelines don't really comment on fosfomycin, the pivmecillinam, things like that, because it just hasn't been studied in this fairly uncommon group of uncomplicated male UTI Dr. Khyati Patel 25:25 and then Dr. Kane. Are there any other antibiotics that we can use in both our men or women population? Yeah. Dr. Sean Kane 25:32 So the one that was definitely very commonly used before, like the string of boxed warnings, was fluoroquinolones. So fluoroquinolones can definitely be used for a three day duration. The main two are going to be Ciprofloxacin or Cipro and levofloxacin or Levaquin. The dose for Cipro is lower. So that's like one clinical pearl. It's 250 B ID, as opposed to the 500 milligrams B ID. And then the same is true with the levofloxacin, 250 daily, as opposed to 500 or 750 the big caveat here is that you don't use avalox or moxifloxacin because it doesn't go in the urine very well and it doesn't treat E coli, which is our main pathogen that we're worried about, Dr. Khyati Patel 26:11 Dr. King, we sort of mentioned earlier that the resistance to photoquinolone is growing and that the ADR list is just kind of severe, right? So these are not going to be your first line antibiotic for the empiric therapy. Dr. Sean Kane 26:25 Yeah. Then the other class that is really interesting, I think experts would like to see more data on are beta lactams, specifically cephalosporins or amoxillin. Clavinate, brand name augmentin, as we mentioned earlier, we're not talking about ampicillin. We're not talking about amoxicillin, because resistance rates are really high, but they aren't high for these other beta lactams. Dr. Khyati Patel 26:47 So we're talking about the resistance rate of less than 10% for E coli, for these recommended beta lactams, like such as augmentin or cephalosporin, there is cephaloxin, which is first gen, there is ceftriaxle, which is also first gen. And then in our third gen, we have the cephaloxane and SEF denier. They're all taken twice a day, and the duration of therapy is five to seven days. Dr. Sean Kane 27:12 And really the problem is that we know that in a petri dish that these are effective in terms of their resistance rates are low enough that they should be good to go. The problem is that either we have some data, more historical data, that beta lactam outcomes may not be as good, and then also they're just less studied for uncomplicated UTI so you'll definitely see it in clinical practice. But the guidelines don't emphasize these beta lactams very much, mostly because of a lack of data. Dr. Khyati Patel 27:36 All right, that brings us to the newest medication discussion, Dr. Kane Pivya, a formulation of pivmecillinam, which was, again, FDA approved in 2024 for adult women with uncomplicated UTI. What do we have on this new drug? Dr. Sean Kane 27:51 Yeah, so the dose is taken three times a day for three to seven days, so kind of a larger pill burden than some of our other drugs. It's a pro drug of me, selenium, which is a beta lactam penicillin based antibiotic. So it works by preventing the penicillin binding protein from making that cell wall. Obviously, if you're allergic to penicillins, this is not a good option for you. And then, in terms of warnings, kind of an interesting one is carnitine depletion, and this relates to it releases something called pivalic acid or pivalate into the body, which binds to carnitine, and then it gets excreted in the urine. So if you were to take this long term, which it's not approved for, then it could eventually cause carnitine deficiency, which I've never seen, but the symptoms are hypoglycemia, muscle aches, fatigue and confusion. So definitely this is not appropriate for, like, long term chronic suppressive therapy, but is FDA approved for a short term Dr. Khyati Patel 28:46 use, and then, as you imagine, the side effects are, obviously, you know, nausea, diarrhea, including C diff, has been noted, candidiasis, so yeast infection, and then, just like other fatal act times, we just have to be worried about the hypersensitivity or the rash. Dr. Sean Kane 29:03 And then, surprisingly enough, Dr. Patel, even though we have 2024 wiki guidelines out there, there's actually another drug that just made it, FDA approved in December 2025 so kind of hot off the press for uncomplicated UTI in women. The drug is called jepo tadasin. The brand name is kind of fun, blue jeppa, and this is approved for uncomplicated UTI, but also for gonorrhea, uncomplicated gonorrhea, and basically it was studied in a non 294 degree studies with nitrofurantoin. So it's nice to see another possibility out there for first line therapy. We kind of don't have time to go too much into the drug during today's episode, but I do think it's nice that other drugs are making it to the market for this really common disease state where kind of our number one therapy is nitrofurantone, which some patients may not be able to take. And it's nice to have other options. Dr. Khyati Patel 29:51 And then Dr. King, you know, we don't again, just like this new drug, blue dropout, we don't have time to talk about everything, but the wiki guidelines do a great job. If you look at their table one, they summarize, not only the treatment, but also the prevention and prophylaxis options, including their recommendations on fluid intake, cranberry, topical, estrogen, probiotics, methadone, mean, so please do check it Dr. Sean Kane 30:16 out so much, and all of that is in our show notes at HelixTalk.com episode 195, so Dr. Patel, from my perspective, a couple of key points. One is uncomplicated. UTIs mean that you have an infection just localized to the bladder, no systemic signs or symptoms of infection. You're not immunocompromised pregnant, you don't have a Foley catheter or urinary catheter, and your urologic anatomy is normal, so that would include men who have UTIs, although that's fairly uncommon, that would still be in the uncomplicated UTI category. Dr. Khyati Patel 30:51 And UTIs are most commonly going to be noted in younger women, and E coli is going to be by far the most predominant urinary pathogen you are looking for that symptom, symptomology, not just the positive urine culture to make that diagnosis, but you then can further go down the route of, you know, doing the urine analysis and urine culture. But most of the times we do approach it with empiric treatment. Dr. Sean Kane 31:17 And that empiric treatment, you can't go wrong with nitrofurantoin or macrobid for most patients for first line therapy. Again, not everyone's going to be indicated, but that's typically our go to first line other recommended options are fosfomycin, Bactrim, PIV met selenium and then certain beta lactam antibiotics can be considered. But again, there's kind of pros and cons to all of these different options. In general, women are going to be treated for three to five days and then five to seven days, Dr. Khyati Patel 31:44 and then some evidence suggests that inferior clinical outcomes for beta lactams. However, the amount of data is generally just lacking for beta lactams, but if you were to use them, the recommended ones are the amoxicillin cloud with on it, and the first and the third generation of cephalosporin, so cephaloxane, hydroxyl, ceftxin and SEF denier. Dr. Sean Kane 32:06 So Dr. tell great review of today's evidence. Again, there's some really good stuff in our show notes at HelixTalk.com episode 195 so we have the wiki guidelines document cited. We have the very old IDSA guidelines, as well as the American family physician guidelines. So take a look, because there's a lot of really good stuff in those as well. So for the listeners, if you want to get email updates when new episodes come out, we have a mailing list that you can subscribe to at our website, HelixTalk.com and we still love those five star reviews and iTunes or wherever you listen to us. So with that, I'm Dr. Kaneand Dr. Khyati Patel 32:40 I'm Dr. Patel, and as always, study hard. Narrator - Dr. Abel 32:43 If you enjoyed the show, please help us climb the iTunes rankings for medical podcasts by giving us a five star review in the iTunes Store. Search for HelixTalk and place your review there to Narrator - ? 32:55 suggest an episode or contact us. We're online at HelixTalk.com thank you for listening to this episode of HelixTalk. This is an educational production copyright Rosalind Franklin, University of Medicine and Science.