Chapter 31: Sexually Transmitted Infections – Drug Treatments

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Welcome to the Deep Dive.

Yeah.

We're here to make complex clinical guidelines both clearer and more actionable.

Exactly.

Today, we're tackling a really major public health issue, sexually transmitted infections or STIs.

I mean, the scale is just huge when you look at the numbers.

We're talking nearly $16 billion annually in the U .S.

alone.

That's staggering.

And what really hits home is who is most affected, about half of all new infections.

They're in young people ages 15 to 24.

Yeah.

And that combination of high rates, the cost, and potential long -term problems like infertility,

it makes this essential knowledge for advanced practitioners.

So our mission today is basically to boil down the key pharmacotherapy guidelines, mostly from the CBC, for managing common STIs.

Right.

We want to get past just reading dense tables and really focus on the core drug regimens, how they work, and the critical decision points you face in practice.

Okay.

So cutting straight to the actionable stuff.

And for any STI treatment, there are two main goals, aren't there?

Always.

First, you have to eradicate the bug, the organism causing it.

Get rid of it.

And second, prevent complications down the line and stop it from spreading further.

Makes sense.

And I'd almost add a third goal, maybe unstated, which is ensuring patient compliance and education.

That's huge, especially with antibiotic resistance being such a growing problem.

Ah, good point.

That resistance theme will likely pop up again.

It definitely will.

Okay.

So where do we start?

Let's kick off with the most common bacterial one in the U .S., chlamydia.

Right.

Chlamydia.

Caused by chlamydia trachomatis.

It's a bit unique.

It's an obligate intracellular parasite.

Meaning it needs a host cell.

Exactly.

It has to get inside a host cell to replicate.

So it kind of shares properties with viruses, even though we treat it like bacteria.

And that's why it's often called the silent infection.

Precisely.

Most people, they don't have any symptoms at all.

But if they do have symptoms, what might we see?

Well, in women, you might see mucopurulent cervicitis.

The big worry, though, is it progressing to PID, Pelvic Inflammatory Disease.

In men, it's typically that thin, clear discharge from the urethra, maybe some pain with urination, dysuria.

And because it's so often silent, screening becomes really important.

Crucial.

The recommendation is yearly screening for all sexually active women under 25.

And older women, too.

Yes.

Older women, if they have new or multiple sex partners, you just have to look for it.

And finding it's pretty reliable these days with the NAT test, right?

Nucleic acid amplification test.

NAT is the gold standard.

You can use urine samples, vaginal swabs.

It's very accurate.

So you get that positive NAT result.

Now comes the treatment decision.

It seems to boil down to azithromycin versus doxycycline.

That's the main fork in the road, yes.

The sources lay out the regimens, but what's the biggest factor driving that choice?

It really comes down to adherence or maybe the risk of nonadherence.

Oh, OK.

Explain that.

Both drugs work very well.

But azithromycin, which is a macrolide, is just a single one gram dose.

One pill.

Done.

So if you have any doubt that the patient might not finish a full week of pills, azithromycin is the safer bet because you know they got the full treatment right there in the clinic.

Guaranteed compliance.

How does it work?

It binds to the bacterial ribosome and blocks protein synthesis,

stops the bacteria from making essential proteins.

So, azithromycin for compliance, even if it costs a bit more initially, what about doxycycline?

Doxycycline is generally less expensive and it's been used for a long time.

It's a tetracycline.

OK.

But the regimen is a hundred milligrams twice a day for seven days.

Seven days.

That's the catch.

Right.

It also inhibits protein synthesis, similar mechanism.

So the clinician has to weigh the cost savings against the very real risk that the patient might feel better after, say, three days and just stop taking it.

Then the treatment fails.

Got it.

OK.

Before we leave chlamydia, what about alternatives?

Yeah.

The really critical issue of pregnancy.

Yeah.

Alternatives are usually for specific situations like treatment failure or allergies.

You might use an older macrolide like erythromycin.

But that one has side effects.

More GI upset.

Yeah.

And it's generally not quite as good.

Or you could use certain fluoroquinolones like afloxan or levofloxacin.

They work differently by blocking DNA gyrase, stopping DNA synthesis.

OK.

But the absolutely critical point, especially for advanced practice, is pregnancy.

Doxycycline and afloxacin are definite no -goes, contraindicated.

So what do you use in pregnancy?

The go -to regimens are either that single one -gram dose of azithromycin or amoxicillin 500 milligrams three times a day for seven days.

Amoxicillin.

And one specific warning.

Avoid erythromycin, estolate, and pregnancy.

There's a known risk of liver toxicity, hepatotoxicity.

Good flak.

OK.

That focus on adherence and resistance really sets us up for gonorrhea.

It does indeed.

Second most common STI.

And with naceria gonorrhea, the rule is dual therapy.

Mandated.

Why is that?

Two big reasons.

First, co -infection.

Patients with gonorrhea very often also have chlamydia.

So you treat for both anyway, just to be safe.

Makes sense.

Treat both usual suspects.

But the second reason is even more critical now.

Antimicrobial resistance.

N -gonorrhea is, frankly, getting really good at resisting antibiotics.

So you need a two -pronged attack.

Exactly.

You have to hit it with two different drugs, using different mechanisms of action to make sure you actually kill it.

Diagnosis is still NAIT primarily.

Yes.

NAIT is standard.

Though, if you suspect resistance, you might need a culture so you can actually test the bug susceptibility.

It just takes longer to get results back.

Right.

So given this resistance threat, what's the current mandatory dual regimen for uncomplicated cases like cervix, urethra, rectum?

The first line combo is ceftriaxone, 250 milligrams as a single shot, AM.

Intramuscular.

TLUS azithromycin, one gram.

Taken orally, also as a single dose.

So both are single doses, just different routes.

Correct.

The ceftriaxone gives you really high sustained drug levels, which is important.

And using azithromycin as the second drug keeps it simple, aligns with the chlamydia single -dose strategy, too.

I notice a really important point in the sources about how quickly things are changing here.

Cefixime, an oral cephalosporin, it's basically not recommended first line anymore.

That's a huge takeaway for practice, absolutely vital.

The bacteria have just developed too much resistance to it.

Wow.

The minimum inhibitory concentrations, the MICs for cefixime against gonorrhea have been creeping up steadily.

So yeah, it's been pushed off the top spot.

It really shows why you have to keep up with current guidelines.

Constant vigilance needed.

OK, so if someone gets this recommended ceftriaxone plus azithromycin therapy,

do they need a follow -up test to confirm cure?

Generally no.

Not for uncomplicated cases treated with the recommended regimen, unless their symptoms don't go away.

But even then, the most likely reason isn't that the drugs failed.

It's usually reinfection.

Ah.

So they got it again quickly.

Exactly.

Which brings us back to the crucial need for partner notification and talking about safer sex practices.

Education is key.

Let's shift gears to syphilis caused by that spiricarid trypanema pallidum.

Here it feels like we move away from complex choices and rely heavily on one main drug, penicillin.

Penicillin is the absolute cornerstone for syphilis, yes.

Can you quickly remind us of the stages?

Sure.

It progresses over time if untreated.

Primary syphilis usually starts with a painless sore, called a chancre, about three weeks after exposure.

Okay.

Then comes secondary syphilis, which is more systemic, maybe a low fever, feeling unwell,

headache, and often a characteristic rash, sometimes on the palms and soles.

Right, the rash.

And then there's latent syphilis, where there are no outward symptoms, but the infection is still there and can be detected with blood tests.

Diagnosis seems a bit more complicated here with all those different tests, VDRL, RPR, FTAA, ABS.

How do we make sense of that?

Yeah, it can seem like alphabet soup, but it's logical.

You need a combination of tests.

Okay.

You start with a non -troponimal test, like VDRL or RPR.

These detect antibodies that are present during active infection, but they aren't specific only to syphilis.

So they show if there's likely an infection.

Kind of, yeah.

They show disease activity.

Then you confirm with a troponimal test, like FTAA, ABS, or MHATP.

These detect antibodies that are specific to the syphilis bacteria.

So non -troponimal first, then troponimal to confirm.

Generally, yes.

And here's the really critical part for monitoring.

You only use the non -troponimal test titers, the VDRL or RPR levels, to see if the treatment worked.

Wait, why not the troponimal tests?

They sound more specific.

They are specific, but the catch is they often stay positive for life, even after successful treatment.

They just show you've been exposed at some point.

Ah, okay.

So they don't reflect current activity.

Exactly.

Only the non -troponimal titers reliably drop after treatment, showing the infection is clearing.

And if you suspect neurosyphilis, then you also need to analyze the cerebrospinal fluid, the CSF.

Got it.

Let's talk about that cornerstone treatment, penicillin G.

Why is it still the undisputed champ for all stages?

It's just consistently effective.

Penicillin G is bactericidal.

It kills the bacteria directly by messing up their ability to build their cell walls.

How does it do that?

It basically binds to enzymes the bacteria need to create cross -links in the cell wall structure so the wall becomes unstable and breaks down.

And the specific type of penicillin G and the dosing depends on the stage?

Correct.

For primary and secondary syphilis, for instance, we use a long -acting form called penicillin G benzathine.

The stage dictates the preparation, the dose, and how long the treatment lasts.

But it's always penicillin G at the core.

And because it's so effective at killing the speuriches,

practitioners need to be ready for something potentially scary.

The Jerrish -Herxheimer reaction.

Yes, absolutely.

JH reaction.

It can be alarming for the patient and for the clinician if they're not expecting it.

What is it exactly?

It's an acute reaction fever, chills, headache, muscle aches, sometimes worsening of the rash usually happening within the first 24 hours after starting treatment.

Why does it happen?

The theory is it's caused by a massive release of inflammatory substances like toxins from the syphilis bacteria as they die off rapidly from the penicillin.

So it's actually a sign the treatment is working but feels awful.

Pretty much.

It usually resolves on its own within a day or so.

Sometimes giving NSAIDs like ibuprofen beforehand might help lessen the symptoms.

Okay.

And finally for syphilis, when is penicillin basically the only option even if a patient says they're allergic?

Two absolutely critical situations, pregnancy and neurosyphilis.

Non -negotiable.

Non -negotiable.

Penicillin is the only treatment proven effective in these cases.

If a pregnant patient has a confirmed penicillin allergy, they must undergo desensitization and then be treated with penicillin G.

Wow.

Desensitization.

Yeah.

Okay.

And for non -pregnant patients with a real allergy.

Then you can use alternatives like doxycycline or tetracycline but the treatment courses are much longer, usually two weeks for early, late and syphilis and potentially four weeks for later stages.

Right.

Much longer than the penicillin regimens.

Okay.

Let's switch from bacteria to viruses now.

Genital herpes simplex virus, HSV.

Okay.

The whole approach changes here, doesn't it?

We're talking control, not cure.

That's the fundamental difference, yes.

HSV caused by either type 1 or type 2 is extremely common,

may be the most prevalent cause of genital ulcers.

And it sticks around.

It does.

The virus hides out, stays dormant in nerve cells and then reactivates periodically.

These recurrent episodes are usually less severe than the very first one, but they happen.

So since we can't actually eliminate the virus.

Our goals shift entirely to managing symptoms during an outbreak and trying to reduce how often outbreaks occur and also reducing the risk of transmission to partners.

What are the main drugs we use for this?

The antivirals.

Yes.

The mainstays are three systemic antivirals, acyclover, valacyclover and famsiclover.

And how do they work?

They all work similarly by inhibiting viral DNA replication.

When the virus becomes active and tries to make copies of itself, these drugs essentially jam the copying machine.

Okay.

I noticed valacyclover and famsiclover are mentioned as pro drugs.

What does that mean?

It means they're inactive when you take them, but the body converts them into the active drug acyclover in the case of valacyclover and pensiclover for famsiclover.

Any advantage to using those?

Yes.

Generally they have better bioavailability, meaning more of the drug gets absorbed.

This often allows for less frequent dosing compared to standard acyclover, which can be a big plus for patients.

Makes sense.

So how do we decide which regimen to use?

The sources seem to outline three main scenarios or tiers of treatment.

That's a good way to think about it.

There are three tiers based on the clinical situation.

Okay.

Walk us through them.

Tier one.

Tier one is for the first clinical episode.

This is usually the most severe, so treatment is longer, typically seven to ten days.

An example would be valacyclover one gram, twice daily.

Got it.

Longer duration for the first time.

What's tier two?

Tier two is episodic therapy for recurrent outbreaks.

Here the treatment is much shorter, maybe one to five days.

Shorter course.

Yes, but the key is timing.

The patient needs to start the medication, ideally during a prodrome, that tingling or itching they feel before lesions appear or at the absolute latest, within one day of the lesion showing up.

So acting fast is critical for episodic treatment.

Absolutely.

An example regimen might be valacyclover 500 milligrams, twice daily for just three days.

It shortens the duration and severity if started early.

Okay.

And the third tier.

For people with frequent outbreaks.

That's suppressive therapy.

This is for patients who have really frequent recurrences, say more than six episodes a year.

So taking medication every day.

Exactly.

It's a daily regimen.

Like a cyclover 400 milligrams, twice daily, or maybe valacyclover 500 milligram or one gram, once daily.

And does it work well?

It can be very effective, often reducing the frequency of outbreaks by 75 % or even more.

It significantly improves quality of life, but it's important patients understand it doesn't completely eliminate the risk of transmission as there can still be some asymptomatic viral shedding.

Right.

Important counseling point.

Okay.

Let's wrap up with two other important conditions where quick decisions matter.

Pelicanflammatory disease, PID,

and human papillomavirus, HPV.

Starting with PID.

We know it's often caused by multiple microbes ascending into the upper genital tract.

Correct.

Often polymicrobial, meaning multiple bugs are involved.

N -gonorrhea and C.

trachomatis are very common culprits, but others can play a role too.

And the big goal with PID treatment is preserving future fertility and reproductive health.

Critical goal.

The first big decision for the practitioner seems to be, can we treat this outpatient or does the patient need to be hospitalized?

That's the immediate assessment, yes.

Certain criteria automatically mean inpatient treatment.

Like what?

You absolutely hospitalized if you can't rule out a surgical emergency like appendicitis or an ectopic pregnancy.

Also, if the patient is pregnant, if they're severely ill, high fever, nausea, vomiting, if there's evidence of a tubo ovarian abscess, or if they simply can't tolerate or follow an oral outpatient regimen.

Makes sense.

So if the PID is judged mild to moderate and none of those red flags are present, what does outpatient treatment usually involve?

It's always a multi -drug regimen because of the polymicrobial nature.

Typically it starts with a single IM shot of ceftriaxone.

For that fast high concentration.

Exactly.

Followed by a course of oral doxycycline.

And sometimes metronidazole is added to cover potential anaerobic bacteria as well.

And if they do need hospitalization?

The IV regimens.

Right.

For severe cases needing parenteral therapy, you'd use IV combinations.

Examples include IV -sifotatin or sifoxatin plus doxycycline, which might be IV initially then switched to oral, or maybe IV -clinamycin plus gentamicin.

Broader coverage for sicker patients.

Got it.

Okay, last topic.

HPV, human papillomavirus, the cause of genital warts.

What's the single most important thing to understand about treating HPV?

The absolute key takeaway is that no treatment eradicates the HPV virus itself.

Period.

So like herpes, we're not curing the underlying infection.

Correct.

The goal of treatment is solely to remove the visible symptomatic warts.

These are usually caused by low -risk HPV types like 6 and 11.

And the concern is more about the high -risk types.

Yes, types like 16 and 18 are the ones strongly linked to cervical dysplasia and cancer, as well as other antigenital cancers.

Warts themselves are generally benign, though bothersome.

So if the goal is just wart removal,

what are the options?

How are they categorized?

We usually divide them into patient -applied versus provider -applied treatments.

Okay.

What can patients use themselves?

Options include things like podaphylox solution or gel or amikimod cream.

These require the patient to apply them correctly over several weeks.

And what can the provider apply in the office?

These are often stronger agents.

Podaphyllin resin, which is different from podaphylox, or chemical treatments like trichloroacetic acid, TCA,

or bicloroacetic acid, BCA.

Cryotherapy, freezing, and surgical removal are also options.

You mentioned TCA, BCA.

Any specific reason?

Yes.

Importantly, TCA and BCA are considered safe to use for wart removal during pregnancy, which isn't true for some of the other treatments like podaphylox or amikimod.

Good to know.

But really, while treating warts is one aspect, the biggest impact regarding HPV comes from something else.

Prevention.

Absolutely.

Vaccination is the game changer for HPV.

Tell us about the recommendations.

HPV vaccination is routinely recommended for adolescents, typically starting around age 11 or 12 up through age 26.

But it's expanded recently, hasn't it?

Yes.

And this is key for practitioners.

Vaccination can now be considered for adults aged 27 through 45 based on a shared decision -making process between the patient and provider.

So discussing it even with older adults in that range.

Given how common HPV is, expanding that prevention window is a major public health advance.

Preventing infection in the first place is far better than just treating warts or monitoring for cancer later.

Okay, that's a great place to land.

We've covered a lot of ground, from bacterial infections needing careful adherence and dual therapy, to viruses where control and prevention are key.

So just to quickly recap the big pharmacologic takeaways,

gonorrhea, it needs dual therapy because of resistance.

Mandatory.

Ceftriaxone plus azipromycin.

Ciflis.

Penicillin G is king for all stages, even needing desensitization in pregnancy.

The absolute cornerstone.

And for viruses like herpes and HPV, the focus shifts away from cure towards symptom control, recurrent suppression, and, crucially, prevention through vaccination for HPV.

Exactly.

And maybe one final thought to tie this back to everyday practice,

remember STIs often travel together.

Right, co -infections.

So, a positive test for one, say gonorrhea or chlamydia, should always prompt you to test for others, especially syphilis and HIV, given the overlapping risk factors.

Good clinical pearl.

And never forget the non -drug part.

Patient education, talking about partner notifications, safe sex, screening those high -risk groups like adolescents, that's just as vital as picking the right antibiotic or antiviral.

That holistic approach is essential.

Thinking about the gonorrhea resistance discussion and the HPV vaccine expansion, it really highlights an ongoing challenge for practitioners, doesn't it?

What's that?

Just how closely everyone needs to monitor these evolving guidelines.

Things change fast with infectious diseases and resistance.

Staying current isn't just best practice, it's essential for effective care and for being good stewards of the antibiotics we still have.

Couldn't agree more.

It requires constant learning and adaptation.

Well, thank you for joining us for this deep dive into STI pharmacotherapeutics.

We hope breaking down these guidelines helps you in your advanced practice.

From the Last Minute Lecture Team, thanks for listening.