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Infectious Disease Special Edition (IDSE), is a newsmagazine for doctors and healthcare professionals in the infectious disease specialty. It publishes six times a year, presenting news and features, as well as review articles about the latest medical developments and practice guidelines relevant to infectious disease specialists, pharmacists, laboratory leaders and others involved in the treatment of infectious diseases.
IDSE's Beaten Pathogens season 1 episode 2 STIs
Hosts
Meaghan Lee Callaghan (MC) [speaker 1 and 4]
Bryan Callaghan (BC) [speaker 2]
Guests
Jeanne Marrazzo, MD (JM) [speaker 5]
Jean-Michel Molina, MD (JMM) [speaker 7]
Victoria Chu, MD (VC) [speaker 8]
Danilo Bacic Lima, MD (DBL) [speaker 9]
00;00;00;22 - 00;00;01;19
Bryan Callaghan (BC) Speaker 1
Alright
00;00;01;22 - 00;00;02;13
Meg Callaghan (MC) Speaker 2
Are you ready?
00;00;02;16 - 00;00;06;25
Speaker 1
Of course I'm ready. I was born ready. I do this for a living.
00;00;06;27 - 00;00;08;23
Speaker 2
No you don't.
00;00;08;25 - 00;00;10;05
Speaker 1
I think I should, though.
00;00;10;08 - 00;00;11;06
Speaker 2
Oh, yeah?
00;00;11;08 - 00;00;14;16
Speaker 1
Well, no, because people have said that I do have a very nice voice.
00;00;14;18 - 00;00;15;21
Speaker 2
You do have a nice voice.
00;00;15;24 - 00;00;20;19
Speaker 1
I have a very nice everything.
00;00;20;21 - 00;00;22;17
Speaker 2
You should introduce yourself.
00;00;22;20 - 00;00;24;25
Speaker 1
I introduced myself at the beginning.
00;00;24;27 - 00;00;26;04
Speaker 2
This is a different episode.
00;00;26;07 - 00;00;26;26
Speaker 1
Really?
00;00;26;27 - 00;00;31;22
Speaker 2
Yep.
00;00;31;24 - 00;00;34;15
Speaker 1
I feel like you could put all this into one episode, but.
00;00;34;17 - 00;00;38;10
Speaker 2
Okay. You know, I'm gonna put other people in.
00;00;38;13 - 00;00;41;16
Speaker 1
Really? What people? There's no one else here.
00;00;41;22 - 00;00;44;23
Speaker 2
The people I've been recording for a year.
00;00;44;25 - 00;00;50;08
Speaker 1
Oh, you're using that stuff? Okay. Okay.
00;00;50;11 - 00;00;53;00
Speaker 2
Why do you think I'm name dropping all these people?
00;00;53;02 - 00;00;53;14
Speaker 1
Well.
00;00;53;15 - 00;00;54;18
Speaker 2
I recorded them.
00;00;54;19 - 00;00;56;13
Speaker 1
Well, good. Now it starts to make sense.
00;00;56;14 - 00;00;56;27
Speaker 2
Do you know
00;00;56;27 - 00;01;17;21
Speaker 1
what I do? No, I don't understand the movie magic. Okay? This is new to me. Okay. I dig holes. You're speaking to a layman. Hi, this is Bryan Callaghan. The layman. I dig holes. This is my wife, Meg Callaghan. She interviews people.
00;01;17;24 - 00;01;18;23
Speaker 2
For a living.
00;01;18;23 - 00;01;22;03
Speaker 1
For a living. I dig holes. You interview people.
00;01;22;04 - 00;01;44;05
Speaker 2
So we thought we'd have a podcast. Yeah. Oh, man! I'm Meg Callaghan. I'm the managing editor of Infectious Disease Special Edition. And I do have a master's in science journalism, so it's not like I'm just ... They can't see you. They couldn't see your face.
00;01;44;07 - 00;01;47;10
Speaker 2
I've only been a journalist for a decade. It's not a big deal.
00;01;47;16 - 00;01;55;02
Speaker 1
Well, I've dug holes for 18 years. Yeah, I'm really good at it.
00;01;55;05 - 00;02;01;24
Speaker 2
So, we talked about a virus.
00;02;01;27 - 00;02;03;09
Speaker 1
AIDS.
00;02;03;11 - 00;02;13;16
Speaker 2
HIV. AIDS is the syndrome that happens if it is uncontrolled. HIV. HIV.
00;02;13;19 - 00;02;20;26
Speaker 2
Now we're going to move and talk about something that is also scary.
00;02;20;28 - 00;02;25;05
Speaker 3
Uh! The anticipation! What are you doing? Just tell me.
00;02;25;08 - 00;02;26;21
Speaker 2
HIV is an STI.
00;02;26;28 - 00;02;27;24
Speaker 1
Okay.
00;02;27;27 - 00;02;31;28
Speaker 2
Formerly known as STD.
00;02;32;00 - 00;02;47;06
Speaker 2
There are other STIs. Correct. And as you may or may not know, I don't know if you really have been talking about it or hearing about it at all, but basically since Covid, other STIs have been coming back and it's not been good.
00;02;47;06 - 00;02;50;12
Speaker 1
Because everyone's ... everyone was stuck in their house for ...
00;02;50;19 - 00;02;56;20
Speaker 2
I don't really know if they know an exact mechanism of what exactly has been going on.
00;02;56;23 - 00;02;59;20
Speaker 1
I think that's when all the dating apps started coming out too.
00;02;59;22 - 00;03;13;14
Speaker 2
I think some of it also had to do with substance use. And the interactions with some of that and but yeah, they're ... okay, okay. .... problems.
00;03;13;18 - 00;03;14;16
Speaker 1
Okay.
00;03;14;19 - 00;03;22;16
Speaker 2
And STIs have been coming back. Syphilis ... Oh! ... has been coming back.
00;03;22;21 - 00;03;26;02
Speaker 3
Like Ben Franklin.
00;03;26;04 - 00;03;44;17
Speaker 4 - Meg narration
Okay. So I've been reporting about this for a while. Months if not years. But he means historical figures. But I, I did a little fact check and Google Gemini says no, Benjamin Franklin did not have syphilis. Very succinct. I'll be a little ...
00;03;44;19 - 00;04;10;26
Speaker 4
I'll expand a little bit on this. It is a common myth that he had it, but there's a lot of people in the past who did or are theorized to have it. A lot of different composers, writers, poets, painters. The gangster Al Capone. Theoretically, Christopher Columbus. Not sure about that. Maybe AI isn't right on that one.
00;04;10;28 - 00;04;42;04
Speaker 4
But anyway, he's talking about syphilis in the past. And, yeah, I think we have that, you know, we have that understanding that it's an old disease, but it's not. It's not. It's still around. And one person who I spoke with about this was Jeanne Marrazzo, who is the CEO of the Infectious Diseases Society of America. She formerly held many titles.
00;04;42;06 - 00;05;01;26
Speaker 5 -- Jeanne Marrazo (JM)
So right now, I am the CEO of the Infectious Disease Society of America. And prior to that, I was the sixth director of the National Institutes of Allergy ... Institute of Allergy and Infectious Diseases. Prior to that was at the University of Alabama at Birmingham for seven years. And before that, most of my career in Seattle, University of Washington.
00;05;01;28 - 00;05;20;25
Speaker 5 - JM
I have had a career mostly focused on sexually transmitted infections, with an emphasis on reproductive tract infections in women, including vaginal infections, and have also been involved in studies of HIV prevention in women, including PrEP.
00;05;20;27 - 00;05;30;25
Speaker 4 - Meg narration
And I spoke to her at CROI 2026, in Denver, where she had just given a talk about STIs and the rise of infections.
00;05;30;27 - 00;06;02;19
Speaker 5 - JM
And syphilis—really since we introduced PrEP, and there's a lot of debate about how much that has contributed—has taken off dramatically in the last decade. So we we've just seen relentless increases, largely in men who have sex with men and to some extent in, men who had sex with women. On top of that, what we're seeing in the last kind of 5 to 7 years is the reemergence, tragically, of congenital syphilis, i.e., syphilis that happens during pregnancy.
00;06;02;21 - 00;06;12;29
Speaker 5 - JM
And we have gone from just a handful of cases in this country, maybe 15 years ago, to over 3,900 cases in 2024.
00;06;13;02 - 00;06;33;15
Speaker 4 - Meg narration
And the year with the last available data, 2023 had 279 infant deaths or stillborns. That's according to the CDC or HHS. And Dr. Marrazzo says that that number is probably an undercount because syphilis during pregnancy can cause miscarriage.
00;06;33;18 - 00;07;01;06
Speaker 5 - JM
So, it's really like [an] incredible failure of the public health system. So, what you're really seeing is kind of an epidemic that is getting a foothold, and especially for pregnant women with syphilis, really affecting a very marginalized population that has challenges with access, challenges with self empowerment, even survival in some cases.
00;07;01;08 - 00;07;10;11
Speaker 4 - Meg narration
So what could be done about it? Dr. Marrazzo said we're kind of a standstill when it comes to diagnostics and treatments.
00;07;10;14 - 00;07;22;03
Speaker 4 - Meg narration
Diagnostics are the same that they have been for a long time, and treatments are the same that they have been for a long time, which is mostly penicillin-based.
00;07;22;05 - 00;07;30;22
Speaker 4 - Meg narration
And there have been penicillin shortages. So, you have to play into that.
00;07;30;24 - 00;07;57;11
Speaker 5 - JM
So, we've been struggling with that a lot, and it comes with a ton of challenges because syphilis is the great imitator. That's what Sir William Osler actually called it, famously. We still don't have a great diagnostic test. We still can't reliably distinguish recurrent [or] infection treatment failure from repeat infection. It's just a very challenging diagnosis to make sometimes.
00;07;57;14 - 00;08;13;06
Speaker 5 - JM
And we're still using penicillin to treat it. So, it's not like we have great options and we don't really have good oral options. You can use doxycycline to treat it. Do that for a couple of weeks, but, you know, it's still not really optimal.
00;08;13;08 - 00;08;21;27
Speaker 4 - Meg narration
And there was some new data that she highlighted that you really only need one shot of penicillin G for early syphilis.
00;08;22;02 - 00;08;46;29
Speaker 5 - JM
There's a nice recent study looking at ... comparing the use of single-dose intramuscular benzathine penicillin versus three weeks of that dose in treating early syphilis, including a people with HIV. And they are noninferior. So, given that we have penicillin shortages, strongly recommend that people trust the data and use just a single dose in early syphilis.
00;08;47;00 - 00;09;11;05
Speaker 5 - JM
They don't need to treat people longer just because they have HIV. So, that's the story with syphilis. There are some vaccine efforts going on. Some fantastic researchers. It's just a tough organism to pin down immunity to.
00;09;11;08 - 00;09;15;06
Speaker 2 - MC
I wanted to talk to you about gonorrhea.
00;09;15;09 - 00;09;19;01
Speaker 2 - MC
Which is a bacteria. It's not a virus.
00;09;19;04 - 00;09;21;24
Speaker 1 - BC
But, see, it's treatable.
00;09;21;26 - 00;09;23;07
Speaker 2
It is.
00;09;23;10 - 00;09;26;02
Speaker 1
So it's like: Listen.
00;09;26;05 - 00;09;30;25
Speaker 2
Well, they all ... well ... Syphilis is also treatable.
00;09;30;27 - 00;09;31;09
Speaker 2
Yep.
00;09;31;12 - 00;09;31;25
Speaker 1
Yes.
00;09;31;27 - 00;09;33;10
Speaker 2
Earlier stage syphilis is the easiest.
00;09;33;10 - 00;09;54;21
Speaker 1
Yes, no, if you let it go crazy, you're done. Yeah. But, so we're talking about gonorrhea. But listen gonorrhea is treatable. So, it's like in the grand scheme of things, if you're ... if anything's going to happen and you get a little gonorrhea, like you just take some medicine. Antibiotics, is it? Mhm. And you just ... and you know what.
00;09;54;23 - 00;09;57;05
Speaker 1
Just be more careful next time.
00;09;57;07 - 00;10;00;05
Speaker 2
Well, except, so ...
00;10;00;07 - 00;10;01;29
Speaker 1
Uh-oh. Is gonorrhea worse now?
00;10;01;29 - 00;10;02;29
Speaker 2
It is.
00;10;03;00 - 00;10;06;04
Speaker 1
Oh, God. It just couldn't relax.
00;10;06;05 - 00;10;08;13
Speaker 2
No, it's working too hard.
00;10;08;17 - 00;10;08;26
Speaker 1
Oh, no.
00;10;08;26 - 00;10;10;05
Speaker 2
It's working too hard.
00;10;10;12 - 00;10;15;08
Speaker 1
So, it's ... Because it's like, ‘everyone's just figuring out ways to get rid of me. I gotta do my thing really quick.’
00;10;15;09 - 00;10;17;06
Speaker 2
So, there's some resistance.
00;10;17;08 - 00;10;28;20
Speaker 5 - JM
But gonorrhea is the ultimate shapeshifter. And you can already see effects on gonorrhea in the men who have been followed through these cohorts.
00;10;28;22 - 00;10;32;06
Speaker 4 - Meg narration
That's Dr. Marrazzo again.
00;10;32;09 - 00;11;02;22
Speaker 5 - JM
So, they acquire in the population markers for resistance that are worrisome for ultimately moving us towards losing the cephalosporins, which is our last line of resistance for treatment right now of gonorrhea. Although—so note that, we've got to be very careful about that—we haven't seen frank ceftriaxone resistance in any of these cohorts. But really worth paying attention to.
00;11;02;24 - 00;11;30;26
Speaker 5 - JM
The good news about gonorrhea is that we have two new antibiotics, which is pretty exciting. And they're both approved by the US FDA. They ... one was approved last month and one was approved in December. It's pretty unprecedented in my career that there have actually been two new STD antibiotics or STI antibiotics. It's like, wow. One is zoliflodacin, which is ... they're both DNA synthesis inhibitors, similar to the quinolone ciprofloxacin.
00;11;30;28 - 00;12;07;19
Speaker 5 - JM
But they work on different sites, that involve the gyrase in zoli's case and topoisomerase in gepotidacin’s case. They're both oral. Zoli is given as a single dose. Gepo is given as two doses 12 hours apart. Zoli ... Both of them had efficacy that was in the low 90% relative to standard of care. So that's acceptable. And both got approved on that basis.
00;12;07;22 - 00;12;37;02
Speaker 5 - JM
The cautions that people should know about with zoli are that it should not be used in pregnancy. And there's testicular toxicity in animal models. And if you read the package insert, it mentions that and it mentions that patients should know about that. But I don't really know what we're supposed to tell patients. So, it's one of those situations where you're ... it's going to be interesting to see what the guidance says, because it's probably a safe drug, but that is worth noting.
00;12;37;02 - 00;13;04;13
Speaker 5 - JM
So, we don't know what that really means. And then gepotidacin is already approved in many places for the treatment of urinary tract infection, uncomplicated urinary tract infection. It's a little bit more complicated because it has some GI side effects, including diarrhea. I shouldn't say it's more complicated, but it does have some GI side effects. There are drug interactions you got to worry about with drugs that prolong the QTc interval.
00;13;04;15 - 00;13;20;03
Speaker 5 - JM
So the thing to think about is how are you going to use these drugs in practice? Are you going to sort of ... now that they're both approved, are they going to both be available and made available? What should the individual provider do if they have a case of gonorrhea? I would say I mean ceftriaxone is perfectly fine. It is an injection.
00;13;20;05 - 00;13;42;29
Speaker 5 - JM
Not everybody loves an injection. But if that's your standard of care, there's no reason to not use that. If you want to use an oral agent. You know, I would take a look at what these costs are. We don't know what the costs are going to be yet [and] how widely available they are. And then for programs that are recommending them, they've got to think about, again, how to introduce these drugs so that we don't get resistance to them really quickly.
00;13;42;29 - 00;14;05;12
Speaker 5 - JM
And there are some models that I talked about this morning that say, like, both should be rolled out at the same time. There's also some modeling in the lab that shows that there might be the ability to induce cross resistance. So, if you roll out zoli, you might induce some changes that favor the ultimate development of gepotidacin. So, just some kind of nerdy considerations.
00;14;05;12 - 00;14;21;12
Speaker 5 - JM
But given that we don't have and haven't had new treatment options for ... oral treatment options for gonorrhea, really, since we used quinolones and we can't use them anymore because resistance is off-the-charts, they're really important things to think about.
00;14;21;15 - 00;14;50;17
Speaker 2 - MC in convo with JM
I'm wondering, so there's so much especially when you're doing ... we're ... when we're talking about HIV, there's so much discussion between oral medications and injectables and pros and cons with people's lifestyles or societal needs and whatever. How does that fall into like ... that's great that they have this new oral option that might be expensive, and some of these people that have STIs might have problems with housing insecurity or other things. Yes. So, how does that fit in?
00;14;50;19 - 00;15;17;25
Speaker 5 - JM
So, great question. The neat story ... I can't speak so much to gepotidacin because I don't know what the plans are for extending approval to other countries and for access. So, that's going to be important to find out. Zoliflodacin is really cool because—not to say it's better, but it's just different—in that it was developed through something called the GARDP, which is the Global Antibiotic Research and Development program.
00;15;17;26 - 00;15;44;27
Speaker 5 - JM
And it's a unique public–private partnership that raises money and gets these agreements with pharma to move these drugs along the pathway to development, because, you know, these drugs are generally not going to be profitable, right? You don't make a single-dose gonorrhea treatment to become rich and retire. You do it because there's a global need and because you want to make the drug available to people who really need it.
00;15;44;27 - 00;16;11;13
Speaker 5 - JM
So, what GARDP is pioneering, I would say, is if you look at the way that zoli was developed, it was started with funding from NIH, from NIAID. So they NIAID funded the early-phase trials. And then as it moved into the later-phase trials, the phase 3, and then the big multicenter trial that got the FDA approval recently, that was funded with GARDP involvement.
00;16;11;13 - 00;16;39;27
Speaker 5 - JM
So, that means that they have negotiated agreements that then allow for rapid access and rapid approval in countries low and middle income countries where it's really needed. So, I think that says that that's hopefully going to say at least that one will be available sooner rather than later and hopefully at a cost that's accessible for programs. Most of us, most of the places that treat STIs don't necessarily charge patients, right.
00;16;39;28 - 00;16;51;20
Speaker 5 - JM
You know ... your public health clinics, your sexual health clinics. I mean, if patients have insurance, that's great, but you want to be able to make sure you can get the patient treatment available for free.
00;16;51;23 - 00;16;54;16
Speaker 2 - MC
So.
00;16;54;19 - 00;17;04;00
Speaker 2 - MC
There's the three STIs ... The big three. ...that we talk ... the big three. Syphilis. Chlamydia.
00;17;04;04 - 00;17;04;12
Speaker 1 - BC
Oof.
00;17;04;19 - 00;17;26;06
Speaker 2
Gonorrhea. Right. They have been trying to find ways to prevent all of these things. All three, you know, syphilis, chlamydia, gonorrhea. And it is called doxyPEP. Doxycycline.
00;17;26;08 - 00;17;27;00
Speaker 1
And does all of.
Speaker 2.
Eh.
00;17;27;00 - 00;17;55;13
Speaker 5 - JM
So that was another big part of my talked about doxycycline post-exposure prophylaxis, which is taking a dose of doxycycline within 72 hours of unprotected sex. This has been demonstrated in men who have sex with men to decrease the subsequent acquisition of both chlamydia and syphilis by anywhere from 60 to 70%. Very effective. No effect on gonorrhea.
00;17;55;14 - 00;18;51;01
Speaker 5 - JM
Because gonorrhea has long been either resistant to tetracycline or gets resistant very fast when you expose it to tetracyclines or doxycycline. So, that intervention has taken off like wildfire in many places. San Francisco and Seattle, where I presented data from this morning, were two of the jurisdictions that implemented this very early, like in 2023. And as I talked about this morning in both places, you have seen really remarkable declines in syphilis in certainly in men, and in Seattle, even in women, which is really shocking because there have been a couple ... there's at least one other trial of using this approach in women, in cisgender women in Africa, in Nairobi, that did
00;18;51;01 - 00;19;19;29
Speaker 5 - JM
not show an effect. But it was partly because women probably weren't really using the product. So, they looked at levels of doxycycline in hair and it was present in only 20%. So, was it, you know, was it that the reason that didn't work? We don't know. But the Seattle study showed not only was it really declining like about 50% in the in the post period from what you would have expected to see if you just kept that curve of what was happening before going on.
00;19;20;01 - 00;19;44;17
Speaker 5 - JM
It also reduced the number of infections in women, cisgender women, which was really surprising. And we don't really know why. It could be because, there's an effect on men, including some men who are having sex with women in those sexual networks where you've got a lot of syphilis. Who knows? But people were surprised by that and somewhat excited.
00;19;44;20 - 00;20;00;05
Speaker 5 - JM
There is another large study underway to look in the United States at whether this will work when given to women in a trial similar to others that have been done. So, it'll be interesting to see what happens.
00;20;00;07 - 00;20;28;29
Speaker 5 - JM
So, I think that this is a pretty exciting intervention. A lot of countries, organizations have come up with recommendations to implement it. The European CDC just issued guidance in January, which is similar to our CDC, which is to definitely use it or offer it in men who have sex with men. There's not enough evidence in women,
00;20;29;02 - 00;21;00;22
Speaker 5 - JM
cisgender women. Transgender women, I should mention, were included in the MSM studies and experienced a similar decline. So, it's pretty clear for MSM and others who sex with men and for trans women, there's a demonstrated benefit. For cisgender women, we really don't know, although that Seattle study is intriguing. The World Health Organization is very close to finalizing guidelines, which we hope will be out sometime this year.
00;21;00;24 - 00;21;10;10
Speaker 5 - JM
So it's clearly taken off. It's going to have an effect. My view is that ...
00;21;10;13 - 00;21;28;08
Speaker 2 - MC
Doxycycline is a very tried and true antibiotic that can treat a lot of different things. For instance, sometimes when you have a bad tick bite, you get doxycycline. You would know that because you've been on it.
00;21;28;11 - 00;21;30;04
Speaker 1 - BC
I took it? You did.
00;21;30;06 - 00;21;31;06
Speaker 6
For a tick bite.
00;21;31;07 - 00;21;38;26
Speaker 1
Oh hell yeah. So, wait, so you're telling me that stuff doesn't become resistance to it, resistant to it?
00;21;38;26 - 00;21;40;19
Speaker 2
That we have to put on the side.
00;21;40;21 - 00;21;44;16
Speaker 2
No, we have to put that on the side, because maybe. But,
00;21;44;19 - 00;21;47;08
Speaker 1
Well, that makes sense, because that's just the natural progression.
00;21;47;09 - 00;21;48;21
Speaker 2
But do you know what PEP is?
00;21;48;23 - 00;21;50;11
Speaker 1
Pep? Oh, I know what pep is.
00;21;50;12 - 00;21;51;18
Speaker 2
No.
00;21;51;20 - 00;21;54;24
Speaker 6
No, P-E-P. It's an acronym.
00;21;54;26 - 00;21;55;18
Speaker 1
Yeah, I know how to spell it.
00;21;55;20 - 00;22;05;00
Speaker 2
No, post-exposure prophylaxis. So, we talked about with HIV pre-exposure prophylaxis, people that are just like ...
00;22;05;01 - 00;22;06;19
Speaker 1
Wait, is that also PEP?
00;22;06;21 - 00;22;08;24
Speaker 2
That's Prep.
00;22;08;26 - 00;22;23;18
Speaker 2
PrEP is like you ... the way that you live your life, which may not be something you choose, or it could be some behaviors you're choosing, it makes you high risk, so you're taking something before you’ve been ...
00;22;23;21 - 00;22;25;05
Speaker 1
Yeah I know what PrEP is. You’re, you’re ....
00;22;25;08 - 00;22;32;07
Speaker 2
So, PEP is different though. PEP is you think you've been exposed, but you don't have it yet.
00;22;32;10 - 00;22;32;25
Speaker 1
Okay.
00;22;32;28 - 00;22;34;01
Speaker 2
So, there's a window.
00;22;34;04 - 00;22;34;26
Speaker 1
So, like when ...
00;22;34;28 - 00;22;36;14
Speaker 2
So, like for rabies.
00;22;36;17 - 00;22;45;05
Speaker 1
Yeah. So, like when I got bit by that raccoon and I almost got ... no. When I got bit by the tick. And so they give me that to make sure that I didn’t ...
00;22;45;07 - 00;22;49;15
Speaker 2
No, you, you had symptoms. So, that wasn't PEP. But yeah.
00;22;49;16 - 00;22;51;01
Speaker 1
I did get rabies. You're right.
00;22;51;02 - 00;23;00;02
Speaker 2
Yeah. No, rabies is 100% fatal. You don't have rabies.
00;23;00;04 - 00;23;32;13
Speaker 4 - Meg narration
So, to clarify, my husband did not have rabies and never has had rabies, but he has taken doxycycline just like a lot of other people in the world. But how did this get to being a PEP drug for STIs? At ESCMID 2026, I was able to have a quick talk with Jean-Michel Molina, professor of infectious diseases at the University of Paris, who is super well-known for being one of the first to study this.
00;23;32;15 - 00;23;49;08
Speaker 7 - Jean-Michel Molina (JMM)
I'm Jean-Michel Molina. I'm an MD, PhD. I’m the head of the infectious disease department at the Saint-Louis and Lariboisière Hospitals in Paris, and I'm a professor of infectious disease at the University of Paris Cité.
00;23;49;10 - 00;23;54;06
Speaker 4 - Meg narration
So, I asked him, how did you start to study this?
00;23;54;09 - 00;24;28;23
Speaker 7 - JMM
I mean, why did we study doxyPEP to start with? You know, we conducted ... that was like more than ten years ago now, one of the initial studies on HIV PrEP, the how to prevent HIV acquisition among MSM. And in that study called IPERGAY, that was conducted with the community, actually. And that's why it was called IPERGAY because we worked hand-to-hand with the community to do the study, which was very successful, actually, the most successful PrEP study ever done.
00;24;28;25 - 00;24;56;05
Speaker 7 - JMM
I would say that actually, pushed the WHO to recommend oral PrEP for MSM. And during the course of the study, we documented a high rate of STIs. We couldn't believe the rate was so high. And then we said, ‘well, what could we do to prevent STIs?’ Because we had the population at high-risk that would be adherent to the visit at least.
00;24;56;10 - 00;25;28;00
Speaker 7 - JMM
And so I, you know, looked at the literature, see what we could do. And I thought doxycycline would be probably the best strategy to use. And because we are using already PrEP, I thought an on-demand PrEP, I thought we would not want to use a a daily regimen, and also because as an ID physician, I know that in order to reduce the rate of AMR you need to use as little as possible antibiotics treatment.
00;25;28;00 - 00;25;55;07
Speaker 7 - JMM
So, we said doxyPEP would be a good strategy, and it has been used in other settings to prevent, for example, Lyme disease or to prevent leptospirosis with the same dosing regimen, 200 mg after exposure, after tick bite or after ... And so I said, ‘well, this sounds like a good strategy. Let's try it.’ And we had very little time to do it.
00;25;55;07 - 00;26;05;02
Speaker 7 - JMM
So, we implemented an amendment to the protocol and tested the strategy. And it was open-label because we couldn't pay for a placebo. And ...
00;26;05;04 - 00;26;17;09
Speaker 4 - Meg narration
And what did they find? Really good results with chlamydia and syphilis. Not really anything with gonorrhea.
00;26;17;12 - 00;26;47;28
Speaker 7 - JMM
And then we presented the data, but we were very cautious because we knew giving antibiotics as a prophylaxis is an issue. And, you know, previous studies for gonorrhea have shown that if you do that, you increase resistance. And that's the reason why we picked up doxycycline, because gonorrhea is already has already become resistant to doxycycline everywhere—lower level resistance or even high level high level is more less frequent.
00;26;48;00 - 00;27;15;15
Speaker 4 - Meg naration
So, what did he do? They set out to replicate the data. Two more studies again, another one in France and one in the U.S. Because he was hesitant. You know, you don't want to be pushing towards more resistance. But at the same time, if you have an easy option to help prevent infection, that could be so great for the community.
00;27;15;18 - 00;28;00;05
Speaker 7 - JMM
So, the initial study was published in 2018. And, so our U.S. colleagues were very interested to reproduce the data. They also had to face some pushback from some ID physicians or microbiologists would say, ‘well, it's not a good thing to do.’ But eventually, we ... the two studies confirmed the data, show also ... saw a very strong decline in syphilis and chlamydia incidence and gonorrhea, depending on the background resistance, you have a lower efficacy, but still some efficacy.
00;28;00;07 - 00;28;04;02
Speaker 2 - MC
But so,
00;28;04;05 - 00;28;38;08
Speaker 2 - MC
There are many people that are working in, maybe HIV, STI clinics or, you know, there's a lot to like that's very focused towards like the LGBT community, specifically men who have sex with men, that are prescribing, you know, you get a like your pills you get for your Crohn's. They get like a big bottle have how many, you know.
00;28;38;10 - 00;28;40;12
Speaker 1 - BC
Like they take two a day.
00;28;40;14 - 00;28;43;06
Speaker 2
They ... if they've been exposed, they take them.
00;28;43;12 - 00;28;46;09
Speaker 1
And then they stop when after a certain time.
00;28;46;13 - 00;28;52;16
Speaker 2
You only take you take like a dose or two. I again I have to go back to what they said ...
00;28;52;19 - 00;28;53;22
Speaker 1
I take like nine pills a day for the rest of my life.
00;28;53;24 - 00;28;56;07
Speaker 2
Okay. They're not ... I just ... I didn't mean like that.
00;28;56;08 - 00;29;07;18
Speaker 1
No, no I don't mean it like that. I'm not being like, oh well, you have to ... no, I don't mean it like that. Hey, congratulations. More power to you. That's awesome. I'm just saying, like, nine pills every single day.
00;29;07;18 - 00;29;08;21
Speaker 2
I know. And they're big ones.
00;29;08;21 - 00;29;18;21
Speaker 1
For the rest of my life. They're like horse pills. I know, and I'm just shoveling down handfuls of them. They're like. M&Ms at this point. Oh, it's terrible.
00;29;18;25 - 00;29;19;12
Speaker 2
I know.
00;29;19;16 - 00;29;25;11
Speaker 1
But you know what? I don't even know. I guess it's a lot better than being in a lot of pain. I'll tell you what.
00;29;25;14 - 00;29;26;07
Speaker 2
That's.
00;29;26;09 - 00;29;32;14
Speaker 1
That's for sure. But I don't get to see all those really nice nurses anymore.
00;29;32;16 - 00;29;35;04
Speaker 2
I'm sure you'll have a colonoscopy one day soon.
00;29;35;06 - 00;29;41;19
Speaker 1
I cannot wait till my next colonoscopy. You’re such a weirdo. So I can catch up with all of them. They were so nice.
00;29;41;21 - 00;29;43;05
Speaker 2
They were nice.
00;29;43;07 - 00;29;47;19
Speaker 1
You know, all the people that ... all the healthcare, honestly.
00;29;47;22 - 00;29;52;20
Speaker 2
Can we talk back about ... So doxyPEP is what it's called.
00;29;52;20 - 00;30;00;14
Speaker 1
The one that's and good against the big two but not gonorrhea. And it's no one just trying to sabotage it because ...
00;30;00;19 - 00;30;02;05
Speaker 2
I don’t think big gonorrhea is out there.
00;30;02;08 - 00;30;07;03
Speaker 1
Well, no, I'm just saying because they're like, ‘oh, so you have the drug that takes care of everything,’ like ...
00;30;07;05 - 00;30;10;17
Speaker 2
Well, but there's some pushback,
00;30;10;20 - 00;30;12;16
Speaker 1
Because it's like a monopoly.
00;30;12;18 - 00;30;30;19
Speaker 2
No, I don't think doxyPEP ... it’s such a generic drug. I don't think that that's the thing. I think it's that, there are some people that think you should not be prescribing an antibiotic for post-exposure prophylaxis.
00;30;30;21 - 00;30;35;01
Speaker 1
Say that how I can understand.
00;30;35;02 - 00;30;43;28
Speaker 2
Oh. I'm sorry. Antibiotic resistance is not great, right? Bad thing. Well, and the ...
00;30;44;01 - 00;30;48;18
Speaker 1
Antibiotic resistance bad.
00;30;48;21 - 00;31;04;04
Speaker 2
I mean but people die of resistant infections, especially in places where they don't have as good health care. Access is bad, is bad. So maybe don't willy nilly give people antibiotics.
00;31;04;09 - 00;31;07;08
Speaker 1
Because now they're, you're building up the resistance to it.
00;31;07;13 - 00;31;11;08
Speaker 2
But then the other people will be like, this is.
00;31;11;10 - 00;31;34;26
Speaker 7 - JMM
So then now we have to be cautious still to select the population. We might benefit the most from this strategy and we still need to monitor AMR. So we know that using doxy, as expected you increase the rate of resistance to gonorrhea. But that's not a big deal because it's not a drug that we use for treatment of gonorrhea because the rate of resistance is already very high.
00;31;34;29 - 00;32;05;11
Speaker 7 - JMM
So, the impact on AMR in the microbiome is also very limited so far. So it seems like the impact is so far limited. My still my concern is, really not to select a strain of syphilis or chlamydia that would become resistant because if that's the case, then you have a colonial dissemination quickly in the population. So so far we haven't seen that.
00;32;05;13 - 00;32;13;22
Speaker 4 - Meg narration
And there was actually some other reassuring data presented at estimate this year. And I got to talk to this person while I was there.
00;32;13;25 - 00;32;40;28
Speaker 8 - Victoria Chu (VC)
So my name is Victoria Chu. I'm an assistant professor at University of California, San Francisco. I'm a pediatric infectious disease specialist. And, I do research on antimicrobial resistance and transmission of microbes within the health care community. Overview. I mean, it's actually pretty reassuring for the microbiome. We're not seeing a lot of major disruptions to the microbial community.
00;32;40;29 - 00;33;04;29
Speaker 8 - VC
What we are seeing, in some of the research is that there's an increase in tetracycline resistance gene amount. And so doxycycline is a type of antibiotic that belongs in the tetracycline class. So it's not too surprising that when you give doxy pep and provide that pressure on the gut microbiome, that you'll see an increase in those resistance genes.
00;33;05;01 - 00;33;10;13
Speaker 4 - Meg narration
Okay. But what does that mean for the people who are prescribing doxyPEP to their patients?
00;33;10;15 - 00;33;46;01
Speaker 8 - VC
What that means clinically, though, is still a little up in the air. Because it really matters who a type of bacteria are picking up and increasing their amount of tetracycline resistance genes. There's been more studies coming out from different parts of the world, where they're seeing some increases in, resistant, Staph aureus, although overall, the amount of Staph aureus colonization in doxyPEP users has gone down compared to non-users.
00;33;46;04 - 00;34;15;04
Speaker 7 - JMM
You know, doxycycline has been used, as I said, for decades for treatment. So now we're using a bit more doxy. That's why, we have to select the population again. There are population, especially because of syphilis, the rise in syphilis and or you know, chlamydia in MSM can be a problem, especially when you have a lymphoid granuloma, which is a very symptomatic and very painful infection.
00;34;15;04 - 00;34;39;24
Speaker 7 - JMM
But other than that, it's not a big deal. It's going to be an important issue for young women because of the impact on fertility. Same is true for gonorrhea and syphilis. That's the main issue today because of the increase of congenital syphilis, and because syphilis is a disseminated disease, it's not like a local mucosal infection. It's rare.
00;34;39;24 - 00;34;55;14
Speaker 7 - JMM
We've gonnococal infection. With chlamydia, it never happens. It's local dissemination ...
00;34;55;16 - 00;35;05;02
Speaker 4 - Meg narration
So I set out to find someone who's actually prescribing this in their clinic. And that person was friend of the magazine.
00;35;05;05 - 00;35;37;22
Speaker 9 - Danilo Bacic Lima (DBL)
My name is Danilo Bacic Lima. I am an infectious diseases clinician educator working in New York City in specializing in sexual health, SDI, and HIV. I work in an urban environment and our patients come from every walk of life. We have a diversity of patients from every sex, sexual orientation, gender for different from different experiences. Most of the patients that I see here are, living in the Bronx, in New York City.
00;35;37;23 - 00;35;42;24
Speaker 9 - DBL
And it's just something that is very fulfilling and joyful to do every day.
00;35;42;27 - 00;35;44;19
Speaker 4 - Meg narration
But what is doxyPEP?
00;35;44;21 - 00;36;05;26
Speaker 9 - DBL
Yeah, I think that a lot of people have heard the name doxyPEP. Sometimes even the patients themselves might come to us and ask us about about it. Oh, can you give me doxyPEP? And I think that people in the sexual health space, people who are HIV clinicians, they may have heard about it and they know of doxyPEP.
00;36;05;28 - 00;36;15;07
Speaker 9 - DBL
But I think that the challenge is reaching a broader audience. And, you know, internists and everyone else who can be part of prevention.
00;36;15;09 - 00;36;31;03
Speaker 4 - Meg narration
And another reason why I spoke with Dr. Bacic Lima is not only is he a friend of the magazine and prescribes this medication, but he also did a review article for us on this exact topic and has reviewed the literature.
00;36;31;09 - 00;37;02;10
Speaker 9 - DBL
And there have been randomized clinical trials that have shown that if people take two pills of 100mg doxycycline, that is 200mg in total after sex, they can reduce their chances of having chlamydia and syphilis and to a lesser extent, gonorrhea. So what the studies have shown is that is that there is a two thirds reduction in the incidence of gonorrhea and syphilis.
00;37;02;10 - 00;37;20;07
Speaker 9 - DBL
And, you know, many of the studies and the real world experiences shows that the reduction is more concentrated in chlamydia and syphilis. And the effect on gonorrhea is inconsistent. And in several studies it is not shown to be effective.
00;37;20;09 - 00;37;40;23
Speaker 4 - Meg narration
And that's what Dr. Molina and Dr. Chu had explained before about resistant profiles for gonorrhea. But doxyPEP is recommended for men who have sex with men for the prevention of chlamydia and syphilis, but not for cisgender women.
00;37;40;26 - 00;38;14;12
Speaker 9 - DBL
Yes, we don't have any, randomized clinical trial confirmatory data that it works in cisgender women. There was a clinical trial done in cisgender women in Kenya, who were prescribed doxycycline PEP, doxyPEP. But the trial did not work. It didn't work in that population. However, a subgroup of the patients were prescribed doxyPEP had drug level analysis.
00;38;14;12 - 00;38;48;28
Speaker 9 - DBL
I think it was hair level hair drug level analysis, and the drug levels were very low, so they were not taking the drug. You know, there are reasons also pharmacokinetic/pharmacodynamics to suspect that doxycycline concentration in vaginal tissue may not be as robust. So we're still trying to understand whether it could work and who this would be working in and discuss all of these unknowns with patients.
00;38;49;00 - 00;39;10;22
Speaker 9 - DBL
There are patients who have heard about it that are not, MSM or transgender women who come and ask me, can I take doxyPEP? I really want it. It seems very exciting. And I tell them, ‘hey, these are all the risks and the benefit is really uncertain. Do you really understand this?’ And I do a lot of shared decision making.
00;39;10;24 - 00;39;40;10
Speaker 9 - DBL
Usually people., then after the conversation, after they understand the lack of data, they, they don't want to, to take it. But if they really want it and they are okay with it, I do prescribe it to them, acknowledging that, it may not work. The benefit is uncertain. But if they really, really, really do and they are really, empowered in their sexual health, I have I have sent it on occasion.
00;39;40;12 - 00;39;54;13
Speaker 4 - Meg narration
Okay. So what does he do when a patient who would be indicated for this prevention method when they come into the clinic, how does he talk to them?
00;39;54;15 - 00;40;34;15
Speaker 9 - DBL
Yeah. So I think that first of all we have to understand who this is for, who are the populations for which we have robust evidence that it works. And those are a men of sex with men and transgender women. Those are the people in whom doxyPEP has been proven to work in studies. I do not routinely offer it to people who are not MSM and sex with men or transgender women, but if they are very interested in it, sometimes I will have a discussion about the unknowns and make a patient centered decision.
00;40;34;17 - 00;40;59;15
Speaker 9 - DBL
But who is this for? MSM and transgender women. That's the first question. And then in the studies, some of the people who were included were people who had had already a diagnosis of bacterial STI, if they had chlamydia, if they had syphilis, if they had gone away, those would be the people that likely most will benefit from doxyPEP.
00;40;59;21 - 00;41;20;29
Speaker 9 - DBL
And sometimes the way that I approach it is when they are seeking care for one of those STIs. The other situation that I approach is when people are seeking care for HIV PrEP and I just broach the topic. I asked them, ‘have you heard of doxyPEP? You know, it's been talked about, what have you been told about it?’
00;41;21;06 - 00;41;40;20
Speaker 9 - DBL
And sometimes people will say, ‘yeah, I've been told about it, I know this,’ and I can have a conversation with the patient about it, and sometimes they haven't heard about it. And I just, explained to them that it is a way to prevent sexually transmitted infections. And I explain what it is, the antibiotics, when to take it.
00;41;40;20 - 00;41;54;22
Speaker 9 - DBL
And I asked them if they're interested in it. And some people might say, ‘no. You know, I'm not very sexually active or I only have sex with one person. We're mutually monogamous. It's not for me.’ Some people will say, ‘well, that sounds great. I would like that. I want that prescription.’
00;41;54;25 - 00;41;58;06
Speaker 10 - Meg in convo with Danilo
Do you think that having.
00;41;58;09 - 00;41;58;29
Speaker 4
HIV.
00;41;59;00 - 00;41;59;26
Speaker 10
Prep.
00;41;59;28 - 00;42;00;29
Speaker 4
And knowing.
00;42;00;29 - 00;42;09;24
Speaker 10
How to talk about that with your patients, that now moving to talk about doxyPEP that that has given you some experience that translated or no?
00;42;09;28 - 00;42;42;06
Speaker 9 - DBL
Yeah. I think that, when we learn about talking about sexual health and medical school, maybe it's not the way that you will end up talking about sexual health with your patients. Right? You have to see other clinicians talking about it. You have to do it in a way that feels effective to you and consistent with your values, and also gets to the meat of the question helping people live happier, fuller and healthier sexual lives.
00;42;42;07 - 00;43;05;28
Speaker 9 - DBL
You know? So definitely the way that I talk about PrEP has evolved and changed over the years, and the way that I talk about has evolved and changed in parallel. I will say, though, that sometimes when we are talking about both in the same appointment, HIV PrEP and doxyPEP patients may conflate the two or confuse the two.
00;43;05;28 - 00;43;32;06
Speaker 9 - DBL
Or think about, oh, this one is before. This one is two pills, this one is after which is which. So we have some handouts to patients that have pictures and show what is what and have clocks drawn on them. And people can actually look at those, they can take a picture and have it on their phone so that they understand what is for what in case they forget.
00;43;32;09 - 00;44;01;02
Speaker 9 - DBL
And I think it's very helpful also to have written materials that you can hand out to your patient so that, you know, if you gave a lot of information and they're a little bit overwhelmed, then that can be a resource that they can go to. Another way that I think we can use technology in our favor. A lot of people use electronic medical records that have a, text that you can save, for example, smart phrases, smart phrases.
00;44;01;08 - 00;44;25;28
Speaker 9 - DBL
And I have created some that I send as patient messages explaining this is the antibiotic. It's two pills. It's not one. This is when you take it. I also explain the main side effects, the most common side effects people sometimes can or oftentimes can have some gastrointestinal discomfort or nausea when they take doxycylcine. So I tell them, hey, take it with food.
00;44;26;00 - 00;44;51;02
Speaker 9 - DBL
It's, you know, with some food, most people feel a little bit more comfortable. You may have some nausea, so people know what to expect. And now we're approaching the hot season, sunny season, photosensitivity. If you're in the sun for a long period of time, your threshold to get sunburns gets lower with toxicity. So I, I have all of those things written out and I explain to patients as well.
00;44;51;05 - 00;45;00;17
Speaker 9 - DBL
And it's also very helpful because if I forgot to say one thing, it's there. So there's some, recursive, you know, mechanism that.
00;45;00;20 - 00;45;37;19
Speaker 2 - MC
Another thing that, Danilo said to me, which I thought was interesting, is that, he will be counseling about HIV Prep, and doxyPEP and PrEP and PEP are different there for different things and for someone that maybe, you know, it can be confusing, it can be confusing. And he gave a little bit of advice about maybe splitting up the conversations, having a lot of like fliers, handouts that.
00;45;37;21 - 00;45;40;20
Speaker 1 - BC
Have your own flier for PEP and your own flier for PrEP
00;45;40;22 - 00;45;52;07
Speaker 2
A take-home message that, like, you're not doing these the same, HIV Prep you need to take, if you're if it's an oral pill, you need to take it constantly. Yeah. No, continue to.
00;45;52;07 - 00;45;53;28
Speaker 1
Take it. If you don't take it then.
00;45;53;29 - 00;45;57;16
Speaker 2
And the doxyPEP is take it if you think you've been exposed.
00;45;57;17 - 00;46;02;20
Speaker 1
See they have to change that then, because that is way too close. That is bad marketing.
00;46;02;27 - 00;46;04;19
Speaker 2
I know, but they're scientists.
00;46;04;19 - 00;46;34;09
Speaker 1
They're not. I know they're scientists, but it's like guys like, but this is where you have to start dealing with the human condition. Like, yes, you're a scientist. You're very smart in this field. Usually they don't know how to, like, interact with the masses because they're, you know, in their own world. You need to tell them if you if the only difference between these two things is an R, you're going to confuse the normal person.
00;46;34;12 - 00;47;02;24
Speaker 1
That's it, say so there's prep to do it. If, if, if you know like you're getting ready you're prepping. Change pep. It makes no sense. It has a if it has to be something like reactive like like plan B was perfect because it's like what plan A didn't work. So like it has to be it has to be some sort of plan.
00;47;02;24 - 00;47;05;00
Speaker 2
B c that is a marketing person.
00;47;05;01 - 00;47;07;15
Speaker 1
Exactly. Yeah. You need to get marketing involved.
00;47;07;16 - 00;47;08;14
Speaker 2
Oh, okay.
00;47;08;16 - 00;47;10;09
Speaker 1
Why are they doing this?
00;47;10;11 - 00;47;11;10
Speaker 2
I don't know.
00;47;11;11 - 00;47;13;10
Speaker 1
Because.
00;47;13;13 - 00;47;42;08
Speaker 1
The scientists get. Tell those scientists to get back in the lab. Marketing needs to take over.
00;47;42;10
Speaker 2
So, you know, there's this is a space that has so much stigma.
Speaker 1
Yeah. Because everyone's like, well, just don't do it, you know? Yeah. But listen again, you're that's fine for you if abstinence or you know or and monogamy it's like that's everyone. It's a preference thing and that's fine. Especially if everyone's consenting and safe. And these people are trying to be safe.
Speaker 2
They're trying to be safe.
Speaker 1
They're trying to be safe. So just provide them the tools they need to be safe. Agree or disagree?
Speaker 1
We're not here. We're not here to judge.
Speaker 2
No, that's not.
Speaker 1
Our job. That's not our job.
Speaker 2
No, no.
Speaker 2
I think, I think that's all I have to say about STIs.
Speaker 1
Okay. Now, what's the third one?
Speaker 2
Well, let's take.
Speaker 1
A break. No, I'm on a roll. Let's do it. Come on.
Speaker 4
Beaten pathogens is a new podcast from Infectious Disease Special Edition, which is a magazine from McMahon Group. You've been listening to me. Meaghan Lee Callaghan, managing editor and my husband and layman extraordinaire, Bryan Callaghan, reporting help from Landon Gray and Ethan Covey, our engineer and musician is Gianni Pizzi. Editing help from Don Pizzi and Brian Dunleavy. Copy editing Kristen Jannacone and Madison Fiedler.
Speaker 4
Special thanks to our team members Leona Smith, Dave Kaplan, and Lillie Onday. Our publication director is Joe Malichio, and our editorial director is David Bronstein. And thank you for listening.