Loading summary
Transcript9 lines
- [00:01]
A
Close your eyes. Exhale. Feel your body relax and let go of whatever you're carrying today. Well, I'm letting go of the worry that I wouldn't get my new contacts in time for this class. I got them delivered free from 1-800-contacts. Oh, my gosh, they're so fast. And breathe. Oh, sorry. I almost couldn't breathe when I saw the discount they gave me on my first order. Oh, sorry. Namaste. Visit 1-800-contacts.com today to save on your first order.
- [00:28]
B
1-800-contacts.
- [00:30]
C
It's tax season, and at Lifelock, we know you're tired of numbers, but here's a big one you need to hear.
- [00:36]
B
Billions.
- [00:37]
C
That's the amount of money and refunds the IRS has flagged for possible identity fraud. Now, here's another big number. 100 million. That's how many data points LifeLock monitors every second. If your identity is stolen, we'll fix it, guaranteed. One last big number. Save up to 40% your first year. Visit lifelock.com podcast for the threats you can't control Terms apply.
- [01:10]
D
Antibiotics, we're wonderful pills but don't ever think we'll cure all of your ills so every time you feel a bit under the weather don't always think that we can make you better Take us for the wrong thing that's dangerous to do when you really need us we could stop working for you so please don't end up paying the price Always
- [01:34]
B
take your doctor's advice the antibiotic song. Is that not the best thing ever? Every time somebody asks me every winter, hey, can I have some Zithromax for my sore throat, even though I haven't talked to you, like, in two years, by the way, how are you? Can I get my Zithromax? I play them this song. Yes, it's true. People love their antibiotics. And one of the most misused antibiotics that we really do need to protect and safeguard because we need this joker to work is Zithromax. Zithromax is taken for so many wrong things, but we need it for the right things, like what we're going to talk about here, which is pprom. But could you imagine a world where there's just no Zithromax? These people don't have any antibiotics. Oh, my goodness. Without antibiotics, what are we going to do? What are we going to do without our Zithromax? But we do need to protect this. All right, let's set this up here very quickly. We're going to talk about surprise Zithromax and what maybe could be the best Zithromax regimen for pprom, preterm pre labor rupture of membranes. Okay, now the benchmark, the gold standard, the go to the first line is still IV amp and erythro. That's historic. This thing works for latency. Remember, it's intravenous for the first two days, followed by oral amoxylin and erythromycin for five, for a total of seven days of antibiotic coverage to try to hit and ward off subacute infection, which typically is the result or the cause of rather preterm pre labor rupture of membrane. So amp and erythro followed by amoxylin and erythro. The problem is that sometimes we can't get erythromycin or a patient can't tolerate it though it's not a true allergy, you know, whatever, but can still take Zithromax. Zithromax has come on the scene and it's been on the scene for a long time as an alternative. Now let me say this very clearly. Zithromax is not to be used alone for latency. It's still to be used, typically with ampicillin. But the question remains, what is the best dose for Zithromax for latency for ppom? Because even ACOG says, look, there's different protocols. I don't know, you kind of pick one, they all kind of do something. It's better than nothing. And if you can't get erythromycin, just use Zithromax in whichever flavor you find the most appealing. But we do have data, so let me just briefly, even though I'm in the intro, let me give you some data here as to how confusing this can look like starting in 2019. All right, so this was a retrospective study in 2019 that found no difference in latency between a single dose versus a multidose erythromycin regimen. But these studies did not measure actual drug concentration at the site of vaccine, meaning the amniotic fluid and the uterus. Alright, so 2019, they're like, hey, I don't know, to give it as a single dose, 2 grams or 1 gram, whatever, versus multi dose, meaning daily for five days, no change in latency. So everyone's like, oh, okay, but remember here, they didn't actually check antibiotic levels in the amniotic fluid in that 2019 retrospective study. There was also, listen to this guys, no difference in the incidence of chorio or neonatal outcomes when comparing different dosing regimens of the azithromycin versus erythromycin plan. However, there was a little bit more respiratory distress among the five day azithromycin group. So they said hey look, you know what? Nothing really pans out one better than the other. But maybe, maybe in terms of less respiratory distress, maybe just give the single dose. So that favored a little bit in terms of respiratory distress, a single dose versus the five days of azithromycin, even though there was no change in latency or other neonatal outcomes. 2019. All right, now watch this. Hold on now we're still in the intro. However, a 2024 Single center retrospective study from Annals of Pharmacotherapy found significantly higher rates of histological chorio with single dose azithromycin compared to a five day regimen with a single dose. It was 62% and it was 46% with a five day regimen. So 2019, they're like, I don't know, no real difference. Maybe a little advantage to a single dose. And then in 2024 they're like oh no, oh no, don't do a single dose. There's higher rates of histological chorio. Remember I said histological. That's placenta pathology, not clinical. But histological chorio with a single dose. So do the five day course. Okay, do you see why we're doing this? Because it's confusing. Now here's the catch. In 2025, this is just last year. Notice we're walking down the line and we're still in the intro. 2019, no real difference. 2024. Oh no, use the five day course. That brings us to last year, 2025, where a systematic review of international guidelines found that out of 17 clinical practice advisories or guidance, only six of them said hey, we don't really know what the best antibiotic regimen is. So out of all of these different guidances for preterm pre labor rupture of membranes, 17 that were reviewed in 2025, Six. Six said, look, it's too ambiguous, we don't really know. We need much more data. And so not real sure as of right now. This brings us. Guys, this brings us to March of 2026 in the Gray Journal that's the AJOG because now we have data and these authors did something pretty neat. They tried to compare the pharmacokinetic parameters of 1 gram of Zithromax versus 500 milligrams daily dosing of Zithromax for 5 days for preterm pre labor rupt of membranes and they tried to see which one maintained amniotic fluid concentrations better, meaning above a certain mic, minimal inhibitory concentration. So this is one of the first times that now we're looking not just at clinical outcomes, but looking at amniotic fluid drug levels where it really matters. Okay, so this is kind of a big deal. So this just came out March of 2026 in the gray Journal, adding more information and I'm going to tell you what they said. Likely the best way to go for a Zithromax dosing for pprom. Okay, so remember, we're still doing ampicillin. They still need that for GBS coverage. But in cases or at times when erythromycin can't be used, then here's a question. What is the best way to dose and to give azithromycin? I love it. Finally, we've got better data on this. It's brand new, just came out in March of 2026 and the title is this Azithromycin in Preterm Premature Rupture of Membranes. I know, stick with it. It says premature. We haven't used that in a long time, but whatever. I'm just reading you the title. Azithromycin in Preterm Premature Rupture of Membranes Population and Pharmacokinetics and Dose Optimization. Now let me read it with the more updated correct term. Azithromycin in Preterm Pre Labor Rupture of Membranes A population and Pharmacokinetics and Dose Optimization. So that's where we're going. We're going to cover this from March of 2026 and I'm just going to leave you with some food for thought about what maybe may be the best Zithromax regimen for PP rom latency. We'll be right back. This is Dr. Chapa's OBGYN clinical Pearl's no Spin podcast podcast family. I'm happy to share information from one of our corporate sponsors, Perspective Medical. In a C section, every second counts, especially when managing postpartum hemorrhage. But traditional surgical draping often hides the very signs that we need to see concealed bleeding around or under the patient. Introducing the OB GYN Physician Designed Hemorrhage View C section drape. It's designed to provide clear and direct visualization of the patient to allow assessment of any concealed bleeding. Now you can recognize hemorrhage earlier and monitor bleeding in real time without compromising the sterile field. Whether you're placing a uterine balloon, or administering uterotonics or assisting in a second stage C section. You now have clear visualization. You need to act fast. So let's be proactive, not reactive, in the recognition and management of hemorrhage. Visit perspectivemedical.org to learn more about the hemorrhage. View C section drape or to request a trial option. So does it happen to you or is it just me? I mean, starting in October, November to December, of course in January. I mean, there's people who I haven't talked to in years and they'll hit me up with some text message, hey, Dr. Chapa, how are you? Do you think you can order me some zither? Max, bro, I haven't talked to you in years. By the way, it's both men and women who reach out, or I met them as, like, you know, some family meeting years ago and they tried to hit me up for antibiotics. No joke. I literally, I really do. I play them the. The little TikTok clip.
- [11:27]
D
Antibiotics were wonderful pills, but don't ever think will cure all of your ills. So every time you feel a bit under the weather, don't always think that we can make you better. Take us for the wrong thing that's dangerous to do when you really need us. We could stop working for you, so please don't end up paying the price. Always take your doctor's advice.
- [11:54]
B
Yep. That was actually also an NHS antibiotic campaign for stewardship, and it's classic and it works. And I send them that audio message and I never hear anything back. I got in trouble with that with my wife once. You did what? I'm like, play them the antibiotics song. You're not going to talk to me in two years and hit me up for antibiotics? Oh, no, no, no. Azithromycin was first published as an alternative to erythromycin for pprom back in 2014, y'. All. It's been over a decade and there's data, but still, you'd figured we'd figure this out in a decade. Nope, not so much. Everyone does it different and I've seen it, even in my own group. Some give 2 grams once and then they're done. Some do 2 grams and then repeat it in three days with another 1 gram dose. Some do a 1 gram, follow it up by 500 milligrams, whatever. And so, because there is no one uniform algorithm here, remember 2025, a review, published guidance are like, I don't know, man, everyone's doing something different, but it's better than nothing. So if you can get erythromycin, which is gold standard, then pick a flavor and use something. This whole introduction of an alternative macrolide like Zithromax first came out in the Green journal again in 2014 when they tried to see if it could give kind of comparable outcomes to the traditional amp enterethro. Well, this study found no difference in latency between the two groups and concluded that the substitution of azithromycin for erythromycin did not adversely affect latency and didn't really have any other impact on maternal or fetal outcomes. So they said, yeah, sure, why not? Go ahead and do that. And then that got picked up in ACOG's practice bulletin number 199 in 2018 that said, yeah, hey, azithromycin can be substituted in situations, quote. For which erythromycin is not available, end quote. But. But they really leave the dosage in a gray zone. Okay, so enter March of 2026 in the gray journal. Oh, that's interesting. I said in the gray zone, and it's in the gray journal. Huh. Wow. That was some kind of weird subconscious thing. I don't know. That's so weird. Okay, so anyway, this was a pretty nice, well designed study. This was a practice. What? Prospective study. My goodness. This was a prospective study of singleton gestations. All had PPROM and they either received one gram one time of Zithromax or 500 milligrams daily for the seven days. All right, so one gram and then whoop, wash your hands of it, you're done. That's it. Or 500 milligrams daily for the seven days of amoxylin. Now, all patients received IV amp. Okay, this is not single therapy. You still got to give the amp for GBS coverage. And they also had PO Amoxicillin to complete the week. Right. This is just swapping out the erythromycin with Zithromax. Now, betamethasone was obviously used here because these were under 34 weeks. So all normal routine stuff, although specific aspects of care were done at physician discretion and weren't dictated by the study. All that the study said is, if you've got PPROM, you're in this EGA timeframe, give steroids, please give either 1 gram Zithromax or 500 milligrams for seven days and give your standard treatment of ampicillin per routine. Okay, so what they did was then they looked at plasma levels, so they drew mom's blood and they Did a pre dose, a 1 to 4 and 12 to 24 hours post dose and then every 24 hours thereafter to see what happens. So before they get any dose, and then followed it up in sequential time periods to see what's going on in the maternal plasma. Now, Participants in the 500mg once daily group had plasma samples collected prior to their next dose to see if it kind of fell down. Now here's the nice thing. We get serum samples, other people have done that, but they checked amniotic fluid samples which were using a non invasive way. Okay. So it's not like they were, you know, sticking through the abdomen. These were unsanitary pads. So they actually got to look if there was some kind of drug activity in the amniotic fluid. Oh, that's brilliant. Brilliant. Multiple oral dosing regimens were then simulated to estimate the amniotic fluid exposure over a seven day interval. So while there was true per patient interventions and analysis, they then looked at different ways to dose the oral antibiotic based on what they found on a kind of a simulation model to see what that would look like with what they found with the plasma and on the sanitary pads to see what a different regimens would actually result over a seven day interval as a simulation. All right, so it was true data extracted as well as a kind of a simulated, a pharmacokinetic study. Okay, so very nice design, super thoughtful, pretty detailed. And included. And included amniotic fluid samples. But, but let's be honest here, Their total number of participants was not great. I know, hold on with me here. 18 participants. 18. That's not 1800, that's 1 8. 18 participants had 101 plasma samples and 223amniotic fluid sampling included in the analysis. I get it, I get it. Please don't send me a message. It's an N of 18. Yes, I'm telling you that. But it's very nicely done. And we don't have this kind of data anywhere else where you can take a look at plasma, you can take a look at amniotic fluid and you can do a simulated model based on what you find to find out the best regimen. So yes, I get it, it's 18. We're dealing with it. But the information that they have here is, is pretty interesting. Daily azithromycin dosing at 500 milligrams daily for seven days. Watch this. Maintained superior amniotic fluid concentration above the MIC for the most common genitourinary pathogens compared to the traditional 1 gram dose. So you do what you want to do. Now I get it. The rebuttal already. I hear some of you thinking it's one gram. What if I do two grams? Dude, hold on. I'm gonna get to that in a minute. I'm gonna get. That's part of the simulation. Okay, but what they checked here is the amniotic flu concentration 1 gram once versus a 500 milligrams daily. And the 500 milligrams daily, kind of keeping a constant level, not kind of a bolus exposure, seemed to work better. Okay. Seem to work better. Now, taking that information, then put that into the simulated model and. And what? They found that after a loading dose, so after you gave a loading dose and then followed that up with 500 milligrams daily for six days, that actually was the best kind of exposure. So let me lay out, there's different levels here of results. One, they found that single dose is not the best. It seems to be better given it daily. Okay, now once we get that in our head, daily seems to be better, then how to give that daily? Based on simulation with an n of 18, with data used from 18 participants, they found that 1 gram once, then 500 milligrams daily for the remaining six days. Or using alternative day dosing, meaning 2 grams once and then 1 gram on days two and four had the best antibiotic coverage. Okay, now, I'm going to give you other information here that we need to know as well. But, but this is pretty eye opening because this gives us kind of a detailed model here based on amniotic fluid concentration. So either one gram once, then five milligrams for six days, or alternative dosing with two grams one time, then one gram on day two and four. All right, so two grams once, then you're done. Then one gram on days two and four. Okay, that seemed to be the best. Now, this pharmacokinetic study challenges that current practice that given a single dose of azithromycin can be the best or is equal to the others. Because based on this, at least on a pharmacology and pharmacokinetic standpoint, that seems to be suboptimal. Okay? Now, while the 1 gram single dose did achieve greater amniotic fluid exposure in the first 24 hours, which you'd expect as a big bolus. Right. As a kind of a loading dose, the daily dosing resulted in significantly higher concentrations throughout the remainder of the seven days. In other words, if you just give one gram once, it's going to wear out. Right. Even tissue levels, it's not going to hang out for seven days. It kind of peaks and then kind of comes down in 24 to 48 hours. Okay, so they found by measuring, actually measuring the levels in the blood and amniotic fluid, you get a more sustained response with daily dosing. Okay? So it seems to be that multi dosing is the way to go, either as a 1 gram dose followed by 500 for six days, or that kind of alternative bolus dosing so that you maintain tissue levels. Okay, I get it. But hold on. There's one big limitation to this. Now, kudos to the Thomas Jefferson folks who put this together because, I mean, to check the blood, check amniotic fluid, come up with a simulated model. Good for them. I'm not doing that. That's a lot of so for you folks in Philly, Good for you. Nice. Nice job. But there is a big limitation here. Big limitation outside of the end of 18 and the fact that using the simulated model, you can only use the numbers that you have, 18 isn't a lot. So maybe it would have been different with larger numbers. But it is what it is. But I'm gonna give you the big limitation here in just a minute. So again, you do what you want to do. I'm going to follow this model because this makes sense to me and it's a good pharmacologic model. Although we definitely need what's missing here. We need this data and we don't have it. But I'm gonna give that. I'll tell you what's missing here in just a minute. Okay? Now before I give you the big limitation, let me tell you something else that's kind of weird that they found in this sample, remember, only in N of 18. But what they found was in those patients who were also undergoing vaginal progesterone for preterm labor prevention. Right? So it's not like they were on progesterone for pprom, but they were on vaginal progestero for kind of, you know, risk reduction for preterm labor. Three patients who received vaginal progesterone supplementation for some reason, those patients had lower concentration of azithromycin in the amniotic fluid. So maybe somehow progesterone may modulate the effect of Zithromax for pprom. Okay? Now take that for what you will again. And that's all they say, like, I don't know, dude, it's three patients. I mean, I don't know what to do with that. But they did find in those three that vaginal progesterone kind of was a barrier. Okay. Kind of. Kind of was like a guard at the door of the placenta, which kind of limited azithromax entry, whatever. I don't know. I have no answer to that, and neither do they. So let me just give you what they say is the strengths of this study, and then I'm gonna give you the big limitation, okay? Because you may be thinking here, wait a minute. We talked about serum levels, amniotic levels, peaks and troughs kind of things, pharmacokinetic stuff. Where's the clinical outcome? Hold on to that in just a minute before I get to that. As the big limitation. As they state as the strength of their study, and I agree with them, the study has several strengths. It's the largest prospective study comparing pharmacologic parameters of azithromycin and amniotic fluid in the setting of pprom, and the only one that they could find with a simulated dosing comparison of different oral regimens. Very good. That's true. They go on to say other pharmacological studies of azithromycin in pregnancy have limited themselves to maternal plasma or have limited amniotic fluid data beyond 72 hours and have not compared different oral dosing regimens. And they did. These authors did just that. So that is a big strength. Now, even though if you read their conclusion, the conclusion is based on our limited data here, it does seem that administration of 500 milligrams azithromycin daily for seven days is superior to a 1 gram once at maintaining amniotic fluid concentrations over MIC. They go on to say in the conclusion, the optimal simulated dosing regimen is a loading dose followed by a daily dose or alternative day dosing. End quote. Okay, so at least they stepped up and said, y' all are confused about something. Nobody knows what to do. We have a proposal. Now, what's the big limitation here? Guys, we're about to wrap this up. Did I mention anything about latency? Did I mention anything about neonatal sepsis? Did I mention anything about clinical chorio iai? No, because that wasn't what they checked. This literally was a pharmacokinetic pharmacodynamic study looking at blood levels and amniotic fluid levels. I don't know what happened, so take that for what you will. But if we're making the deduction. And again, deductions sometimes are valid, sometimes they're scary. But if we're making the deduction that higher serum levels translates to higher amniotic fluid levels. You would think that would translate to better latency. I have no idea. Because this was not a clinical outcome driven paper. This was looking at pharmacokinetics, pharmacodynamics and dosing. So I want to be. I don't want to give any misrepresentation here. While this is very, very nice and it makes a lot of sense and it is big strengths here as they described, we do not know if this clinically was any better. So again, I'm not laughing at them. I'm just saying I read this whole paper. I'm like, oh, we can have better latency. Many less fetal respiratory distress or whatever. And I'm like, where's the rest of it? Where's the clinical stuff, bruh? I got nothing. So I don't know. I do like this. This makes sense to me. I'm gonna propose this to our team. Why not? It makes sense. So in cases or times where we cannot get erythromycin either by shortage or patient tolerance or whatever, Whatever, then we're gonna use Zithromax. And rather than everybody kind of having all these different hodgepodge approaches, I'm gonna propose this because it does make sense. Although when my team's gonna ask me, what's the clinical outcomes? I'm gonna tell them what I told you. I have no idea, but it makes sense to me. So that's why we need to follow this up now with clinical outcomes. Again, we have covered a new publication from March of 2026. This is azithromycin in preterm Premature. Yes, it says premature rupture of membranes and a population in Pharmacokinetics and dose optimization study. Okay, this just came out Again, March of 2026, and the lead author is Roopsa Maling. So good for you guys. For Pennsylvania in Philly, Thomas Jefferson University and One side, which was Wilmington, Delaware. Good for you all for looking into this. We need more information, so I'm going to use it. And why not? But I wish we had the clinical outcomes to support and to augment and to foster that podcast family. As always, we're. Thank you. We're glad you're part of our podcast community. And now that we've done all that, let's take it home. This is Dr. Chapa's obgyn clinical pearls no spin podcast.