What is the recommended prophylaxis treatment for a sexually active individual exposed to common STIs such as chlamydia, gonorrhea, or syphilis?

STI Prophylaxis: Evidence-Based Recommendations

For men who have sex with men (MSM) and transgender women with a bacterial STI in the past 12 months, prescribe doxycycline 200 mg as a single dose within 72 hours after condomless sex (maximum 200 mg per 24 hours) to prevent syphilis, chlamydia, and gonorrhea. 1, 2

Target Population for Doxycycline Post-Exposure Prophylaxis (Doxy PEP)

Primary candidates:

• MSM and transgender women who have had at least one bacterial STI (syphilis, chlamydia, or gonorrhea) diagnosed in the past 12 months 1, 2
• Consider for MSM and transgender women without recent STI diagnosis but engaging in high-risk sexual activities using shared decision-making 2

Current evidence does NOT support doxy PEP for:

• Cisgender women (insufficient evidence)
• Heterosexual men (insufficient evidence)
• Prevention of other STIs beyond syphilis, chlamydia, and gonorrhea 2

Efficacy Data

The 2024 CDC guidelines are based on three large randomized controlled trials demonstrating:

• >70% reduction in syphilis and chlamydia infections 2, 3
• ~50% reduction in gonococcal infections 2, 3

This represents the highest quality evidence available and supersedes older prophylaxis approaches. 1

Dosing Protocol

Regimen: Doxycycline 200 mg orally as a single dose 1, 4

Timing: Within 72 hours after oral, vaginal, or anal sexual contact 1, 4

Critical limitation: Maximum 200 mg per 24-hour period, even with multiple sexual encounters 4, 3

Prescription quantity: Provide enough doses based on anticipated sexual activity until next visit 4

Administration Instructions (Critical for Efficacy)

To prevent esophageal ulceration:

• Take with a full glass of water (≥200 mL) 4, 3
• Take on a full stomach with non-dairy food 4, 3
• Remain upright for at least 1 hour after taking 4, 3

To prevent drug interaction and treatment failure:

• Separate from dairy products by at least 2 hours before AND after dosing 4
• Separate from antacids, calcium, iron, magnesium, or sodium bicarbonate by at least 2 hours 4

Monitoring Requirements

Baseline assessment:

• Bacterial STI testing at all anatomic sites of exposure 1, 3
• HIV screening for HIV-negative patients 1, 3

Ongoing monitoring:

• STI testing every 3-6 months at anatomic sites of exposure 1, 2, 3
• HIV screening per current recommendations 1, 3
• Reassess ongoing need for doxy PEP every 3-6 months 1, 4, 3

Patient Counseling Points

Expected side effects:

• Photosensitivity (recommend sun protection) 1, 4, 3
• Gastrointestinal symptoms 1, 3
• Esophageal erosion/ulceration (preventable with proper administration) 1, 4, 3

Limitations of protection:

• Does NOT prevent Mycoplasma genitalium 2
• Does NOT replace condoms, HIV PrEP, or comprehensive STI prevention 2, 3
• Regular STI screening remains essential 2, 3

Alternative Prophylaxis Scenarios

Post-Sexual Assault Prophylaxis (Different Context)

For sexual assault victims, the 1998 CDC guidelines recommend empiric treatment rather than post-exposure prophylaxis: 1

• Ceftriaxone 125 mg IM (single dose) PLUS
• Metronidazole 2 g orally (single dose) PLUS
• Azithromycin 1 g orally (single dose) OR Doxycycline 100 mg orally twice daily for 7 days

This regimen covers chlamydia, gonorrhea, trichomonas, and bacterial vaginosis simultaneously. 1

Additional considerations for assault victims:

• Hepatitis B vaccination (without HBIG) at initial examination, with follow-up doses at 1-2 and 4-6 months 1
• Serologic testing for syphilis and HIV at 6,12, and 24 weeks 1
• Follow-up STI testing at 2 weeks 1

Pre-Exposure Vaccination

Hepatitis B vaccination is recommended for all unvaccinated patients being evaluated for STIs, as HBV is frequently sexually transmitted. 1

Hepatitis A vaccination is recommended for MSM and persons who use illegal drugs. 1

Common Pitfalls to Avoid

1. Do NOT exceed 200 mg doxycycline in 24 hours for STI prophylaxis, even with multiple sexual encounters—this can increase toxicity without additional benefit 4, 3

2. Do NOT prescribe doxy PEP for cisgender women or heterosexual men—current evidence only supports use in MSM and transgender women 1, 2

3. Do NOT allow patients to take doxycycline with dairy products—chelation reduces absorption and can lead to treatment failure and antimicrobial resistance 4

4. Do NOT present doxy PEP as comprehensive STI prevention—it must be part of a comprehensive approach including condoms, regular screening, and HIV prevention 2, 3, 5

5. Do NOT confuse post-assault prophylaxis with doxy PEP—these are different clinical scenarios with different regimens 1

Antimicrobial Resistance Considerations

While concerns about antimicrobial resistance exist, the 2024 CDC guidelines represent a careful balance between individual benefit and population-level resistance risk. 1 The decision to recommend doxy PEP was based on:

• Substantial reductions in STI incidence in high-risk populations 1
• Ongoing surveillance for resistance patterns 1
• Integration with comprehensive STI prevention strategies 2, 3

International guidance varies, with some countries recommending against widespread use due to resistance concerns, while others support conditional use for high-risk populations. 1 The CDC's 2024 position represents the most current U.S. evidence-based approach. 1