What it is:A grab-bag chapter, not one disease. STIs are grouped by shared transmission route (sexual contact) but the pathogens, presentations, and drugs have almost nothing in common with each other. Gonorrhea and chlamydiaare bacterial, often silent, and frequently travel together. Syphilisis a slow multi-stage spirochete infection. Herpesis viral and never cured, only suppressed. Trichomoniasisis a protozoan you treat with one drug class.
The core problem:Most of these infections are asymptomatic or nearly so, especially in women, which is exactly why they spread and exactly why untreated PID, infertility, and ectopic pregnancy show up downstream. The chapter is less about recognizing dramatic symptoms and more about knowing who to screenand what single dose cures it.
What you do about it:Learn the chapter as five fast reference cards (gonorrhea, syphilis, chlamydia, herpes, trich), each with one dominant regimen you should be able to recite cold, plus the exceptions (pregnancy, penicillin allergy, disseminated disease) that show up on every exam and every real-world consult.
Almost every STI regimen in this chapter is a CDC recommendation, not an FDA-labeled indication.Metronidazole 2 g single dose for trichomoniasis, doxycycline 100 mg BID for chlamydia and gonorrhea coverage, these are practice standards from CDC treatment guidelines that outrun the package insert. When a dose here looks "off-label," it usually isn't wrong, it's just CDC-driven.
Before drilling into each bug, it helps to see the whole board. STIs aren't one category of pathogen, they're five categories that happen to share a transmission route.
| Category | Disease | Organism |
|---|---|---|
| Bacterial | ||
| Gonorrhea | Urethritis, cervicitis, PID, DGI | Neisseria gonorrhoeae |
| Syphilis | Primary → secondary → latent → tertiary | Treponema pallidum |
| Chancroid | Painful genital ulcer | Haemophilus ducreyi |
| Bacterial vaginosis | Malodorous discharge | Gardnerella vaginalisand others |
| Chlamydial | ||
| Chlamydia / NGU | Urethritis, cervicitis, PID | Chlamydia trachomatis |
| Lymphogranuloma venereum | Ulcer + painful lymphadenopathy | C. trachomatis, type L |
| Viral | ||
| Genital herpes | Painful vesicular/ulcerative lesions | HSV-1, HSV-2 |
| Genital warts | Condylomata acuminata | Human papillomavirus |
| Protozoal / Mycoplasmal | ||
| Trichomoniasis | Discharge, itch, "strawberry cervix" | Trichomonas vaginalis |
| NGU (persistent) | Recurrent urethritis | Mycoplasma genitalium |
The handbook organizes clinical presentation by syndromeas much as by organism, because in the exam room you see a syndrome first and a pathogen second. Know which bugs cause which picture:
| Syndrome | Usual suspects | Tell |
|---|---|---|
| Urethritis | C. trachomatis, HSV, N. gonorrhoeae, T. vaginalis, M. genitalium | Discharge, dysuria |
| Genital ulcers, painful | H. ducreyi, HSV | Multiple vesicular/pustular lesions, tender nodes |
| Genital ulcers, painless | T. pallidum | Single, indurated, "clean" looking |
| Salpingitis / PID | C. trachomatis, N. gonorrhoeae | Lower abdominal pain, adnexal tenderness, fever |
| Genital/anal warts | HPV | Papular to exophytic lesions |
Painful ulcer = chancroid or herpes. Painless ulcer = syphilis.That single distinction is one of the highest-yield facts in the whole chapter, and it's exactly the kind of thing a vignette will hinge on.
Neisseria gonorrhoeaeis a gram-negative diplococcus, and humans are its only host. It caused over 16,000 newly reported US infections in 2019 alone, and the CDC has flagged drug-resistant gonorrhea as an urgent-threat pathogen, one of only a handful on that list. That resistance trajectory is why the recommended regimen keeps shrinking to fewer, higher-dose options instead of expanding.
NAATs have replaced cultureas the primary test in most settings, they're fast and highly sensitive. Culture still matters when you need susceptibility data, which is increasingly the point given rising resistance. The CDC and USPSTF recommend annual screening for all sexually active women under 25, regardless of symptoms.
| Infection | Recommended | Alternative |
|---|---|---|
| Uncomplicated cervix/urethra/rectum | Ceftriaxone 500 mg IM once(1 g if ≥150 kg) | Gentamicin 240 mg IM + azithromycin 2 g PO once, orcefixime 800 mg PO once if ceftriaxone unavailable |
| Uncomplicated pharyngeal | Ceftriaxone 500 mg IM once | Consult ID, harder to clear |
| DGI (>45 kg) | Ceftriaxone 1–2 g IM/IV every 12–24 h | Cefotaxime or ceftizoxime 1 g IV q8h |
| Gonococcal conjunctivitis | Ceftriaxone 1 g IM once | - |
| Ophthalmia neonatorum | Ceftriaxone 25–50 mg/kg IV/IM once (max 250 mg) | - |
| Newborn prophylaxis | Erythromycin 0.5% ophthalmic ointment once | Ceftriaxone 25–50 mg/kg IM/IV once (max 125 mg) |
Older regimens paired ceftriaxone with routine azithromycin to cover chlamydia. Current CDC guidance instead adds doxycycline 100 mg PO BID x 7 daysonly when chlamydia coinfection hasn't been ruled out, because gonorrhea and chlamydia coinfect often enough that empiric coverage is the default rather than the exception. Azithromycin dual therapy was scaled back specifically because of rising macrolide resistance in N. gonorrhoeae.
Ceftriaxone 500 mg IM single dose, same as nonpregnant adults, plus azithromycin 1 g PO once if chlamydia isn't ruled out. Tetracyclines (including doxycycline) are contraindicated in pregnancy, so doxycycline is not the chlamydia add-on here even though it is everywhere else. Treatment matters beyond the mother too: untreated maternal gonorrhea causes ophthalmia neonatorum, which is why every newborn gets prophylactic erythromycin ointment regardless of maternal status.
All treatment failures should get culture and susceptibility testing.Given the resistance trend, "the drug didn't work" needs confirmation and workup, not just an empiric re-dose.
Treponema pallidumis a spirochete, spread almost entirely by contact with infected mucous membranes or lesions. HIV coinfection rates run high, particularly in MSM, so a syphilis diagnosis should always trigger an HIV test.
Incubation 10–90 days (mean 21). A single, painless, indurated chancre at the exposure site, heals in 4–6 weeks on its own even without treatment.
Hematogenous/lymphatic spread. Maculopapular rash that classically hits palms and soles, condylomata lata, patchy alopecia. Resolves spontaneously in 1–6 months if untreated.
Positive serology, no symptoms. Early latent <1 year, late latent >1 year or unknown duration. About 28%of untreated latent patients go on to late disease.
Years later. Gummas (granulomatous lesions in any organ), cardiovascular syphilis, or neuro/ocular/otic involvement that can appear at anystage, not just late disease.
Students expect an ulcer to hurt. The syphilitic chancre doesn't, and because it's painless and solitary it's frequently missed or ignored, especially internally (cervix, rectum). That's a major reason syphilis progresses silently to secondary and latent stages.
T. pallidumdoesn't culture well in vitro, so diagnosis leans on dark-field microscopyof lesion material or, far more commonly, serology. Two categories, used together:
Parenteral penicillin G is the only proven therapy at every stage, and benzathine penicillin G is the only formulation effective as single-dose therapy (its long tissue half-life is the whole point; aqueous forms clear too fast for a single shot to work).
| Stage | Regimen (non-allergic) | Follow-up serology |
|---|---|---|
| Primary, secondary, early latent (<1 yr) | Benzathine PCN G 2.4 million units IM x1 | Nontreponemal titer at 6 and 12 mo; fail if not ≥4-fold drop by 12 mo |
| Late latent, unknown duration, or tertiary | Benzathine PCN G 2.4 million units IM weekly x 3(7.2 million units total) | Titer at 6, 12, 24 mo |
| Neurosyphilis (incl. ocular/otic) | Aqueous crystalline PCN G 18–24 million units/day IV(3–4 million units q4h or continuous) x 10–14 days | No repeat CSF at 6 mo if RPR drops ≥4-fold |
Doxycycline 100 mg PO BID or tetracycline 500 mg PO QID for 14 days (early) or 28 days (late latent). Except in pregnancy, where tetracyclines are contraindicated and there is no acceptable non-penicillin alternative, pregnant patients get penicillin desensitizationinstead of a substitute drug. This is one of the few places in pharmacy where allergy doesn't change the drug, it changes the process for giving the same drug.
After treating primary or secondary syphilis, patients can develop fever, chills, headache, myalgia, and worsening of the skin lesions within hours. This is the Jarisch-Herxheimer reaction, caused by the sudden die-off of spirochetes releasing inflammatory products, not an allergic response to the drug. Manage with antipyretics and reassurance; don't mislabel the patient as penicillin-allergic over this.
Test every syphilis patient for HIV.Pregnant patients at high reinfection risk should get monthly nontreponemal titers. Some experts add a second benzathine penicillin dose one week after standard therapy in pregnancy to further reduce vertical transmission risk.
Chlamydia trachomatisis the most common STI in the US. It's an obligate intracellular organism with features of both a bacterium and a virus, which is part of why it behaves clinically the way it does: quiet infections that smolder rather than announce themselves.
NAATs are the recommended test, sensitive and fast on first-catch urine, vaginal swab, or urethral swab. Culture is more specific (near 100%) but only 70% sensitive and takes 3–7 days, so it has largely been replaced except for special circumstances (e.g., forensic cases requiring the highest specificity).
| Population | Recommended | Alternative |
|---|---|---|
| Uncomplicated urethral/endocervical/rectal, adults | Doxycycline 100 mg PO BID x 7 days | Azithromycin 1 g PO once, or levofloxacin 500 mg daily x 7 days |
| Pregnancy | Azithromycin 1 g PO once | Amoxicillin 500 mg TID x 7 days |
| Neonatal conjunctivitis/pneumonia | Erythromycin 50 mg/kg/day PO divided QID x 14 days | Azithromycin suspension 20 mg/kg/day PO once daily x 3 days |
Azithromycin 1 g single dose used to be first-line for its convenience and adherence advantage. Current CDC guidance now prefers doxycycline for its higher efficacy, especially in rectal chlamydia where azithromycin underperforms. Azithromycin remains the go-to when adherence is a real concern, and it's still the pregnancy default since doxycycline is off the table there.
Posttreatment test-of-cure is not routinely neededfor standard chlamydia regimens, they're highly effective. The one carve-out is rectal chlamydia treated with azithromycin, where retesting is recommended specifically because of reduced efficacy at that site. Infants treated for pneumonitis also need follow-up testing, since erythromycin is only about 80% effective in that population.
HSV-1 is classically oral, HSV-2 classically genital, but either can cause either. What actually determines the clinical course isn't which type, it's whether the body has ever seen HSV before.
| Episode type | Definition |
|---|---|
| First-episode primary | First genital infection, no prior antibody to HSV-1 or HSV-2 |
| First-episode nonprimary | First genital infection, but prior HSV exposure (usually oral HSV-1) exists |
| Recurrent | Lesions reappear after the first episode has healed |
PCR for HSV DNA is preferredover viral culture for confirming first-episode genital herpes, faster turnaround and better sensitivity.
There is no cure. Every regimen here is about shortening the course, reducing complications, and reducing transmission, not eradication.
| Situation | Regimen |
|---|---|
| First clinical episode (7–10 days, extend if not healed) | |
| Acyclovir | 400 mg PO TID |
| Valacyclovir | 1 g PO BID |
| Famciclovir | 250 mg PO TID |
| Recurrent, episodic therapy (start within 24h of prodrome/lesion onset) | |
| Acyclovir | 800 mg PO BID x 5 days, or 800 mg TID x 2 days |
| Valacyclovir | 500 mg PO BID x 3 days, or 1 g daily x 5 days |
| Famciclovir | 125 mg PO BID x 5 days, or 1 g BID x 1 day |
| Chronic suppression | |
| Acyclovir | 400 mg PO BID |
| Valacyclovir | 500 mg or 1000 mg once daily |
| Famciclovir | 250 mg PO BID |
Daily suppressive therapy cuts recurrence frequency and severity andreduces asymptomatic viral shedding by 70–80% in patients with frequent outbreaks, which is what actually lowers transmission to partners. Consider stopping after a year to reassess how often recurrences are happening off therapy.
Valacyclovir 500 mg is less effective than 1 gor acyclovir regimens in patients with ≥10 recurrences a year, and famciclovir is less effective for suppressing viral sheddingspecifically. If suppression isn't working, these are the first two things to check before assuming resistance.
Pregnancy:Acyclovir has the longest track record with no evidence of teratogenicity and is the preferred agent. Valacyclovir and famciclovir safety data in pregnancy is less established, though animal data suggests low risk.
Trichomonas vaginalisis a flagellated protozoan, responsible for roughly 6.9 million US cases in 2018 alone, making it the most common curable STI by case count. The inflammatory response it triggers independently raises the risk of acquiring HIV, which is why treating it matters beyond its own symptoms.
Wet-mount microscopyis the simplest, classic method: look for motile, pear-shaped flagellated organisms in vaginal discharge. NAATs are more sensitive and specific and point-of-care rapid tests now exist for office-based testing. Because symptoms overlap heavily with bacterial vaginosis, lab confirmation is required, you can't diagnose this on symptoms alone.
| Situation | Recommended | Alternative |
|---|---|---|
| Women, symptomatic or asymptomatic | Metronidazole 500 mg PO BID x 7 days | Tinidazole 2 g PO once |
| Men, symptomatic or asymptomatic | Metronidazole 2 g PO once | - |
| Persistent/recurrent | Metronidazole 500 mg BID x 7 days | Tinidazole 2 g daily x 7 days |
| Pregnancy | Metronidazole 500 mg PO BID x 7 days | - |
Women get the 7-day BID coursebecause a randomized trial found fewer treatment failures with 7 days than with a single 2 g dose. Men get the single 2 g dosebecause that's what the evidence base for male treatment actually supports, data on alternative or persistent-infection regimens in men is limited enough that treatment failure should prompt an ID consult rather than guesswork.
The old teaching that metronidazole causes a hard disulfiram-like reaction with alcohol has been walked back by the CDC, current guidelines don't formally link the two. Still, most clinicians counsel patients to avoid alcohol during treatment out of caution and because GI upset is already a known side effect that alcohol would only worsen.
Always treat partners simultaneously.This is true across the whole trichomoniasis section: without concurrent partner treatment, reinfection is the norm, not the exception. Retesting is recommended for all sexually active women within 3 months of treatment given high reinfection rates. In pregnancy, metronidazole is pregnancy category B and usable in any trimester; breastfeeding should be interrupted 12–24 hours after a single 2 g maternal dose. Tinidazole is category C and should be avoidedin pregnancy.
These are syndromes and lesser bugs that don't warrant their own full section but come up constantly in practice and on exams. Same core drugs (doxycycline, ceftriaxone, azithromycin) reused in slightly different combinations.
| Condition | Recommended regimen | Key point |
|---|---|---|
| Cervicitis | Doxycycline 100 mg PO BID x 7 days | Add gonorrhea coverage if the patient is at risk |
| Epididymitis, likely C. trachomatis/N. gonorrhoeae | Ceftriaxone 500 mg IM once +doxycycline 100 mg BID x 7 days | Standard combo for sexually acquired epididymitis |
| Epididymitis, insertive anal sex risk | Ceftriaxone 500 mg IM once +levofloxacin 500 mg daily x 10 days | Covers enteric organisms too |
| Epididymitis, enteric organisms only | Levofloxacin 500 mg daily x 10 days | No ceftriaxone needed if gonorrhea/chlamydia ruled out |
| NGU, standard | Doxycycline 100 mg BID x 7 days | Azithromycin 1 g once is the alternative |
| NGU, persistent/recurrent or M. genitalium | Doxycycline x 7 days followed bymoxifloxacin 400 mg daily x 7 days | Two-drug sequence, not a substitution |
| Lymphogranuloma venereum | Doxycycline 100 mg BID x 21 days | Much longer course than routine chlamydia; azithromycin 1 g weekly x 3 weeks is the alternative |
Persistent or M. genitalium-driven NGU gets doxycycline thenmoxifloxacin, not moxifloxacin alone. Doxycycline first lowers the organism burden, which improves the odds moxifloxacin actually clears what's left and helps limit driving further fluoroquinolone resistance. If azithromycin resistance can be ruled out, an azithromycin taper (1 g then 500 mg daily x 3 days) can substitute for moxifloxacin.
Doxycycline is contraindicated, so pregnant patients with LGV get erythromycin base 500 mg PO QID x 21 daysinstead. Same duration, different drug, the pattern repeats from chlamydia and syphilis: pregnancy swaps the drug, not the goal.
Human papillomavirus causes lesions ranging from small papular warts to large exophytic condylomas. Unlike the bacterial/protozoal infections above, treatment here is almost entirely destructive or ablative, not systemic antimicrobial therapy, because there's no drug that eradicates the virus itself.
| Approach | Options |
|---|---|
| Provider-administered | |
| Destructive | Cryotherapy (liquid nitrogen), repeated weekly as needed |
| Chemical | TCA or BCA 80–90% applied to warts, repeated weekly |
| Surgical | Tangential scissor/shave excision, curettage, electrosurgery |
| Patient-applied | |
| Podofilox 0.5% | BID x 3 days, then 4 days off, cycle up to 4 times |
| Imiquimod 3.75% or 5% | At bedtime, 3x/week for up to 16 weeks |
| Sinecatechins 15% | TID for up to 16 weeks |
Vaginal and anal warts are treated with cryotherapy or TCA/BCA only, no self-applied topical agents there, and surgical removal is specifically avoided for vaginal or urethral meatus warts. Site dictates the toolkit as much as the diagnosis does.
| Age group | Regimen |
|---|---|
| 9–14 years | Gardasil 9, 2 doses: day 1 and 6–12 months later |
| 15–26 years | Gardasil 9, 3 doses: day 1, month 1, month 6 |
| 27–45 years | Can be considered on a case-by-case basis, not routine |
Younger adolescents mount a stronger, more durable immune response, so they need only 2 dosesinstead of 3. Routine vaccination starts at 11–12 years old and can begin as early as age 9. Catch-up is recommended through age 26 for anyone unvaccinated or incompletely vaccinated. Gardasil 9 covers types 6, 11, 16, 18, 31, 33, 45, 52, and 58, the mix that drives both genital warts (6, 11) and most HPV-associated cancers (the high-risk oncogenic types).
STI risk reduction and pregnancy prevention are frequently discussed together, but they aren't the same problem, and mixing them up is a real counseling error.
Among all contraceptive methods, condoms (male or female) are the only method besides abstinence that protects against STI transmission.Every hormonal method, the LARC options (implant, IUDs), and permanent sterilization prevent pregnancy but do nothingfor STI risk. A patient on an IUD or the implant still needs condoms if STI exposure is a concern; those methods answer a completely different question.
This matters practically because highly effective contraception can create a false sense of protection. A patient who switches from condoms to a levonorgestrel IUD because it's more effective at preventing pregnancy (failure rate ~0.2% vs. condoms' 18–21% typical-use failure) has notreduced their STI risk at all, and may have inadvertently increased it if condom use drops to zero. Spermicide-containing barrier methods (diaphragm, cervical cap, sponge) carry an added caution: spermicide is not recommended for patients at risk of STIsbecause it can irritate mucosal tissue and potentially increase susceptibility to infection.
Frame this for patients simply: "Your birth control keeps you from getting pregnant. It doesn't do anything about infections. If STIs are a concern, you still need a condom on top of whatever else you're using." That one sentence prevents a lot of confusion.
| Infection | Follow-up | Why |
|---|---|---|
| Gonorrhea | Test-of-cure not routine; culture/sensitivity for anytreatment failure | Resistance concern drives workup of failures specifically |
| Syphilis | Quantitative nontreponemal titers at 6 & 12 mo (early), 6/12/24 mo (late latent) | Fourfold titer drop = cure; failure to drop = retreat |
| Chlamydia | Not routine, except rectal infection treated with azithromycin, and treated infants | Standard regimens are highly effective; those two exceptions aren't |
| Trichomoniasis | Retest all sexually active women within 3 months | High reinfection rate, not usually true treatment failure |
| All bacterial/protozoal STIs | Treat sexual partners simultaneously | Untreated partners are the #1 cause of "recurrence" |