Fellow's pre-read · Infectious Diseases
Sexually transmitted infections
CDC STI Treatment Guidelines 2021 + doxy-PEP 2024 · pre-read 2026-07-07
Pre-read for tomorrow's STI didactic. Regimens are drawn from the CDC 2021 STI Treatment Guidelines (MMWR RR 70-4) and the 2024 doxy-PEP guideline (MMWR RR 73-2). The "What's changed" callout is reviewer synthesis. Not a substitute for the full guideline.
In one line
Most bacterial STIs are cured by a short, specific regimen. The fellow's moves: NAAT the right sites (including rectal/pharyngeal), treat empirically when the syndrome fits, cover chlamydia whenever you treat gonorrhea, stage syphilis to pick the penicillin course, and treat the partners (EPT).◆First-line treatment — the table to know cold
| Condition | Recommended regimen | Key note |
|---|---|---|
| Gonorrhea (uncomplicated) | Ceftriaxone 500 mg IM ×1 (1 g if ≥150 kg) | Add chlamydia cover (doxycycline) if not excluded; pharyngeal GC → test-of-cure in 7–14 d |
| Chlamydia | Doxycycline 100 mg PO BID ×7 d | Azithromycin 1 g ×1 = alternative; azithromycin preferred in pregnancy. LGV → doxycycline ×21 d |
| Syphilis — primary, secondary, early latent | Benzathine penicillin G 2.4 M units IM ×1 | Follow the nontreponemal titer (RPR/VDRL) for a 4-fold drop |
| Syphilis — late latent / unknown duration | Benzathine penicillin G 2.4 M units IM weekly ×3 | Missed dose >9–14 d apart → restart the series (non-pregnant) |
| Neurosyphilis / ocular / otic | Aqueous crystalline penicillin G 18–24 M units/day IV (3–4 M units q4h or continuous) ×10–14 d | Same for ocular & otic syphilis |
| Trichomoniasis | Women: metronidazole 500 mg PO BID ×7 d · Men: metronidazole 2 g PO ×1 | Multi-day for women is the 2021 change (was single 2 g) |
| PID (outpatient) | Ceftriaxone 500 mg IM ×1 + doxycycline 100 mg PO BID ×14 d + metronidazole 500 mg PO BID ×14 d | Low threshold to treat empirically on clinical criteria |
| Genital herpes — first episode | Valacyclovir 1 g PO BID ×7–10 d (or acyclovir) | Recurrent = short course; suppression = valacyclovir 1 g daily |
| Bacterial vaginosis | Metronidazole 500 mg PO BID ×7 d | Not sexually transmitted per se; common co-finding |
| Mycoplasma genitalium | Doxycycline ×7 d → then azithromycin (macrolide-susceptible) or moxifloxacin 400 mg daily ×7 d (resistant/unknown) | Resistance-guided; doxycycline first lowers burden |
◆Syphilis — the staging that drives everything
- Primary = painless chancre. Secondary = rash (incl. palms/soles), condyloma lata, mucous patches, lymphadenopathy. Early latent = acquired <1 yr; late latent = ≥1 yr or unknown.
- Diagnosis = a treponemal + a nontreponemal test (reverse or traditional algorithm). Follow response with the nontreponemal titer (expect ≥4-fold/2-dilution drop).
- Penicillin allergy → desensitize — penicillin is the only recommended therapy in pregnancy and in neurosyphilis.
- Jarisch–Herxheimer reaction: acute fever/myalgia/headache within ~24 h of treatment (not an allergy).
◆Testing & the fellow's habits
- NAAT is the test of choice for gonorrhea & chlamydia — test every exposed site (urogenital, rectal, pharyngeal); extragenital infection is routinely missed on urine-only testing.
- Every STI visit: test for HIV and syphilis; offer HIV PrEP; check hepatitis serologies and give HepA/HepB and HPV vaccines.
- Expedited partner therapy (EPT): give the patient medication or a prescription for partners (gonorrhea/chlamydia) where legally permitted.
What's changed / worth knowing
Reviewer synthesis — not the guideline text.
- Doxy-PEP (CDC 2024): doxycycline 200 mg within 72 h after sex for MSM and transgender women with a bacterial STI in the past 12 months. Cut syphilis & chlamydia by >70% and gonorrhea by ~50% in RCTs. Test for STIs at baseline and every 3–6 months. MMWR RR 73-2, 2024
- Gonorrhea is now monotherapy — ceftriaxone 500 mg alone (azithromycin dropped from dual therapy; the dose doubled to slow resistance). CDC 2021
- Trichomoniasis in women is now multi-day metronidazole (500 mg BID ×7 d), not a single 2 g dose. CDC 2021
◆Likely pimp questions
- First-line for gonorrhea? Ceftriaxone 500 mg IM ×1 (1 g if ≥150 kg).
- Why still cover chlamydia when treating GC? High co-infection — add doxycycline unless chlamydia is excluded.
- Chlamydia first-line, and why doxy over azithro? Doxycycline 100 mg BID ×7 d — better cure, especially rectal.
- Benzathine penicillin: early vs late latent syphilis? 2.4 M units IM ×1 (early) vs weekly ×3 (late latent/unknown).
- Neurosyphilis treatment? IV aqueous crystalline penicillin G ×10–14 d.
- Penicillin-allergic pregnant patient with syphilis? Desensitize — penicillin is the only option in pregnancy.
- Trichomoniasis in a woman? Metronidazole 500 mg BID ×7 d (not single 2 g).
- Outpatient PID regimen? Ceftriaxone 500 mg IM + doxycycline ×14 d + metronidazole ×14 d.
- Who gets doxy-PEP? MSM/TGW with a bacterial STI in the past year — 200 mg within 72 h of sex.
- M. genitalium approach? Resistance-guided: doxycycline then azithromycin (susceptible) or moxifloxacin (resistant).
- Jarisch–Herxheimer reaction? Fever/myalgia within ~24 h of syphilis treatment — not an allergy.
Sources: Workowski KA, et al. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep 2021;70(RR-4) — gonorrhea, chlamydia, syphilis, trichomoniasis, PID, HSV, BV, M. genitalium, EPT. · Bachmann LH, et al. CDC Clinical Guidelines on the Use of Doxycycline Postexposure Prophylaxis for Bacterial STI Prevention, United States, 2024. MMWR Recomm Rep 2024;73(RR-2).