Best ZMax Regimen for PPROM?

0:00This podcast is brought to you by Avocado Mattress, and if healthy, comfortable sleep matters to you, this is one organic brand worth knowing. That's because what you sleep on actually matters. Most mattresses rely on synthetic phones and chemical materials that trap heat, break down over time, or off gas. Avocado does that differently. Their mattresses are handcrafted with natural materials, organic latex, organic wool, and organic cotton, designed to be naturally cooling, incredibly supportive, and long-lasting. They're certified organic by gods and meet multiple non-toxic and safety certifications, made for people who care about their health in the environment without sacrificing comfort. I love that avocado proves you don't have to choose between comfortable, supportive sleep, and your values. And now you can get up to 15% off all avocado mattresses. Just go to AvocadoGreenMatress.com. Get up to 15% off at AvocadoGreenMatress.com. AvocadoGreenMatress.com.

1:00This podcast is sponsored by Talkspace. Last year, I went through many different life changes. I needed to take a pause and examine how I was feeling and the inside to better show up for the ones who need me to be my best version of myself. When you're navigating life's changes, Talkspace can help. Talkspace is the number one rated online therapy, bringing you professional support from licensed therapists and psychiatry providers that you can access anytime, anywhere, live in a busy life, navigating a long-distance relationship, becoming a first step father. Talkspace made all of those journeys possible. I could speak with my therapist in the office. I could speak with my therapist in the comfort of my home. I was never alone. Talkspace works with most major insurers and most insured members have a $0 copay. No insurance, no problem. Now get $80 off your first month with promo code space80 when you go to Talkspace.com. Match with a licensed therapist today at Talkspace.com. Save $80 with code space80 at Talkspace.com.

2:23Take a spoiler on 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. The antibiotic song is that not the best thing ever. Every time somebody asks me every winter, hey, can I have some zither max from 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 zither max? 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 zither max. Zither max 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. Because you imagine a world where there's just no zither max. These people don't have any antibiotics.

3:24Oh my goodness. Without antibiotics, what are we going to do? What are we going to do without our zither max? But we do need to protect this. All right, let's set this up here very quickly. We're going to talk about surprise zither max and what maybe could be the best zither max 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 retro. That's historic. This thing works for latency. Remember, it's intravenous for the first two days followed by oral amoxylin and an retromycin for five. For a total of seven days of antibiotic coverage, to try to hit and ward off subacute affection, which typically is the result or the cause of, rather a preterm pre-labor rupture of membranes. So amp and retro followed by amoxylin and retro. The problem is that sometimes we can't get a retromycin or a patient can tolerate it, though it's not a true allergy,

4:25you know, whatever, but can still take zither max. Zither max 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. Zither max is not to be used alone for latency. It's still to be used typically with ampicillin, but the question remains, well, what is the best dose for zither max for latency for PPROM? Because even if ACOG says, look, there's different protocols. I don't know, you kind of pick one, that they all kind of do something. It's better than nothing. And if you can't get a retromycin, just use zither max 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 multi-dose arithromycin regimen.

5:27But these studies did not measure actual drug concentration at the side of action, meaning the amniotic fluid and the uterus, all right? So 2019, they're like, hey, I don't know, to give it as a single dose, two grams or one 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 choreo or neonatal outcomes when comparing different dosing regimens of the arithromycin versus arithromycin plan. However, there was a little bit more respiratory distress among the five-day arithromycin 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,

6:32maybe just give the single dose. So that favored a little bit in terms of respiratory distress, a single dose versus the five days of arithromycin, 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 choreo with single dose arithromycin 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 choreo, remember, histological, that's placenta pathology, not clinical, but histological choreo with a single dose to do the five-day course. Okay, do you see what we're doing this?

7:34Because 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 pre-term pre-liber 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

8:37of one gram of zythermax versus 500 milligrams daily dosing of zythermax for five days for pre-term pre-labor rupture 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 the 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 is the best way to go for a zythermax dosing for PPROM. Okay? So remember, we're still doing ampicillin. They still need that for GPS coverage. But in cases or at times when an erytheromycin can't be used, then here's the question, what is the best way to dose and to give a zytheromycin?

9:39I 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 a zytheromycin in pre-term premature rupture of membranes. I know stick with it says premature. We haven't used that in a long time, but whatever. I'm just reading to the title. A zytheromycin in pre-term premature rupture of membranes, population, and pharmacokinetics and dose optimization. Now let me read it with the more updated correct term. A zytheromycin in pre-term 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 now it's going to leave you with some food for thought about what maybe, maybe the best zythermax regimen for PP-ROM latency. We'll be right back.

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11:41So 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 to me? I mean, starting in October and November to December, of course, in January, I mean, there's people who haven't talked to you in years and they'll hit me up with some text message, hey, Dr. Choppa, how are you? Do you think you can order me some Zythermax? 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, it's like, you know, some family meeting years ago and they tried to hit me up for an antibiotics. No joke, I really do. I play them the little TikTok clip. Empty biotics, we're wonderful pills, but don't ever think we're all of your reals. So every time you feel a bit under the weather, don't always think the week may make you better. Take a spoiler on thing that's dangerous to do.

12:44When 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. 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. Yeah, I got in trouble with that with my wife once. You did what? I mean, uh, play them the antibiotics long. You're not going to talk to me for even two years and hit me up for an antibiotics. Oh, no, no, no. As it's rummizing, it was first published as an alternative to erythromycin for PPROM back in 2014. Y'all has been over a decade and there's data, but still you 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 two grams once and then they're done. Some do two grams and then repeat it in three days

13:45with another one gram dose. Some do a one gram, follow it up by 500 milligrams. Uh, whatever. And so because there is no one uniform algorithm here. Remember, 2025, a review of published guidance. They're like, I don't know, man, everyone's doing something different but it's better than nothing. So if you can't get erythromycin, which is gold standard, then pick a flavor and use something. This whole introduction of an alternative macrullide like zythromax first came out in the green journal again in 2014. When they try to see if it could give kind of comparable outcomes to the traditional amp and erythro. Well, this study found no difference in latency between the two groups and concluded that the substitution of a zythromycin 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.

14:46And then that got picked up in ACOG's practice bulletin, number one nine nine in 2018. That said, yeah, hey, zythromycin can be substituted in situations, quote, for which erythromycin is not available. 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 by Goodness. This was a Prospective Study of Singleton Justations. All had PPROM. And they either received one gram one time of zythromax or 500 milligrams daily for the seven days, all right? So one gram and then whoop, wash your hands of it.

15:47This podcast is brought to you by Avocado Matress. And if healthy, comfortable sleep matters to you, this is one organic brand worth knowing. That's because what you sleep on actually matters. Most mattresses rely on synthetic foams and chemical materials that trap heat, break down over time, or off gas. Avocado does that differently. Their mattresses are handcrafted with natural materials, organic latex, organic wool, and organic cotton, designed to be naturally cooling, incredibly supportive, and long-lasting. They're certified organic by gods and meet multiple nontoxic and safety certifications, made for people who care about their health in the environment without sacrificing comfort. I love that avocado proves you don't have to choose between comfortable, supportive sleep and your values. And now you can get up to 15% off all avocado mattresses. Just go to AvocadoGreenMatress.com. Get up to 15% off at AvocadoGreenMatress.com. AvocadoGreenMatress.com.

16:47This podcast is sponsored by Talkspace. Last year, I went through many different life changes. I needed to take a pause and examine how I was feeling and the inside to better show up for the ones who need me to be my best version of myself. When your navigating life's changes, Talkspace can help. Talkspace is the number one rated online therapy, bringing you professional support from licensed therapists and psychiatry providers that you can access anytime, anywhere. Living a busy life, navigating a long-distance relationship, becoming a first step father, Talkspace made all of those journeys possible. I could speak with my therapist in the office. I could speak with my therapist in the comfort of my home. I was never alone. Talkspace works with most major insurers, and most insured members have a zero-dollar copay. No insurance, no problem. Now, get $80 off your first month with promo code space80 when you go to Talkspace.com. Match with a licensed therapist today at Talkspace.com. Save $80 with code space80 at Talkspace.com.

17:47You're done. That's it. Or 500 milligrams daily for the seven days of all Mozilla. Now, all patients received IV AMP. Okay, this is not single therapy. They all used to have to give the AMP for GBS coverage, and they also had PO, all Mozilla, into complete the week. All right, this is just swapping out the erythromycin with Zythromax. Now, beta metasone was obviously used here because these were under 34 weeks. So, all normal routine stuff, all those specific aspects of care were done at physician discretion and weren't dictated by the study. All that the study said is you've got PPROM. You're in this EGA time frame. Diff steroids. Please give either 1 grams of Zythromax 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 the Drew Mums blood, and they did a pre-dose, a 1 to 4 and 12 to 24 hours post-dose,

18:50and then every 24 hours or after 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 500 milligrams once daily group had plasma samples collected prior to their next dose to see if it kind of fell down. Now, here's a nice thing. We get serum samples, okay? Other people have done that. But they checked amniotic fluid samples which were done using a non-invasive way. Okay? So, it's not like they were, you know, sticking through the abdomen. These were on sanitary pads. So, they actually got to look if there was some kind of drug activity in the amniotic fluid. Well, 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 perpatient interventions and analysis, they then looked at different ways to dose the oral

19:50antibiotic 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 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. So, I know, hold on with me here, 18 participants, 18. That's not 1800, that's 18 participants had 101 plasma samples and 223 amniotic fluid samples included in the analysis. I get it, I get it. Please don't send me a message. It's an end of 18. Yes, I'm telling you that,

20:50but 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 pretty interesting. Daily is itthromycin dosing at 500 milligrams daily for seven days. Watch this, maintained, superior amniotic fluid concentration above the MIC for the most common genital urinary 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 1 gram but if I do two grams, do hold on, I'm going to get to that in a minute. I'm going to get, that's part of the simulation, okay? But what they checked here is the amniotic fluid concentration, the 1 gram once versus the 500 milligrams daily and the 500 milligrams daily kind of keeping a constant level,

21:50not kind of a bolus exposure seem to work better. Okay, seem to work better. Now, taking that information, then put that into the simulated model and what they found that after a loading dose, so after you gave a loading dose and then follow 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 end of 18, I would data use from 18 participants, they found that 1 gram once, then 500 milligrams daily for the remaining six days, or using alternative day dosing, meaning two grams once, and then 1 gram on days two and four had the best antibiotic coverage, okay?

22:52Now, I'm going to give you other information here that we need to know as well, but this is pretty eye opening because this gives us kind of a detailed model here based on amniotic fluid concentration. So, either 1 gram once, then 500 milligrams for six days, or alternative dosing with two grams one time, then 1 gram on day two and four, all right? So, two grams once, then you're done, then 1 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 a zithromycin 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 kind of a as a loading dose,

23:54the daily dosing resulted in significantly higher concentrations throughout the remainder of the seven days. In other words, if you just give 1 gram once, it's going to wear out, right? Even tissue levels is 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 sound by measuring, actually, measuring the levels in the blood and the 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 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 work. So, for you folks in Philly, good for you, nice, nice job,

24:58but there is a big limitation here, okay? Big limitation outside of the end of 18, and the fact that, you know, using the simulated model, you can only use the numbers that you have, and of 18 isn't a lot. So, maybe it would have been different with larger numbers, but it is what it is. But I'm going to 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 form of kinetic model, although we definitely need the what's missing here. We need this data, and we don't have it, but I'm going to give that, I'm going to 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 an end of 18, but what they found was in those patients who were also undergoing vaginal progesterome for preterm labor prevention, right? So, it's not that they were on progesterome for PPROM, but they were on vaginal progesterome for kind of, you know, risk reduction for preterm labor.

25:59Three patients who received vaginal progesterome supplementation, for some reason, those patients had lower concentration of a zythromiasin in the amniotic fluid, so maybe somehow progesterome may modulate the effect of zythromax 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 progesterome kind of was a barrier, okay, kind of was like a guard at the door of the placenta, which kind of limited a zythromax entry. Whatever, I don't know, I have no answer to that, and neither do that. So, let me just give you what they say is the strength of this study, and then let me give you the big limitation, take, 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.

27:00Before I get to that, as the big limitation, as they state as the strength of their study, and I agree with them, quote, the study has several strengths. It's the largest prospective study comparing pharmacologic parameters of a zythromax in an amniotic fluid in the study in 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, quote, other pharmacological studies of a zythromycin 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. End quote, 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 quote, administration of 500 milligrams is a zythromycin daily for seven days, is superior to a 1 gram once

28:00at maintaining amniotic fluid concentrations over MIC. They go on to saying the conclusion, quote, 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, choreoslash 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 translate

29:01to 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 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're going to have to let better latency. We need a less fetal respiratory distress or whatever. And I'm like, where's the rest of it? Where's the clinical stuff, bro? I got nothing. So I don't know. I do like this. This makes sense to me. I'm going to propose this to our team. Why not? It makes sense. So in cases, in cases where times where we cannot get to rethromize and either by shortage or patient tolerance or whatever,

30:03then we're going to use Zytheromax. And rather than everybody kind of having all these different hodgepodge approaches, I'm going to propose this because it does make sense. Although, when my team's going to ask me, what's the clinical outcomes, I'm going to 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 a Zytheromycin in preterm premature. Yes, it says premature rupture of membranes, a population in pharmacokinetics and dose optimization study. Okay, this just came out again, March of 2026. And the lead author is Rupsa Balling. So good for you guys for Pennsylvania, in Philly, Thomas Jefferson University, and one side, which was Wilmington, Delaware. Good for you offer 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

31:05and to augment and to foster that. Podcast family, as always, we're thankful for 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. Chappas, OBGYN, Clinical Pearls, No Spin Podcast. You're listening to a podcast right now. Driving, working out, walking the dog. If you're into podcasts, chances are you have something to say too. With rss.com, starting your own is free and easy. Upload an episode, and we distribute it to Apple podcasts, Spotify, Amazon Music, and hundreds more. Track your listeners, see where they're from, and start earning from ads like this. Even with just 10 listeners a month. If you've been thinking about starting a podcast, this is your sign.

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