What are the first‑line treatment regimens for common sexually transmitted infections such as chlamydia, gonorrhea, syphilis, trichomoniasis, genital herpes, and HPV‑related genital warts?

First-Line Treatment for Common Sexually Transmitted Infections

For chlamydia, use doxycycline 100 mg orally twice daily for 7 days as first-line therapy; for gonorrhea, use ceftriaxone 500 mg IM (≥150 kg body weight) or 250 mg IM (<150 kg); for syphilis, use penicillin G benzathine 2.4 million units IM; for trichomoniasis, use metronidazole 500 mg orally twice daily for 7 days; for genital herpes, use antivirals for symptomatic episodes; and for genital warts, use patient-applied imiquimod or provider-applied cryotherapy.

Chlamydia (Chlamydia trachomatis)

Recommended First-Line Treatment:

• Doxycycline 100 mg orally twice daily for 7 days 1
• Alternative: Azithromycin 1 g orally as a single dose 2, 3, 4, 5

Key Clinical Points:

• Doxycycline is now preferred over azithromycin due to superior efficacy and concerns about Mycoplasma genitalium resistance to macrolides 1
• Azithromycin remains useful when compliance with 7-day regimens is questionable or for directly observed therapy 2, 4, 5
• Both regimens have cure rates of 97-98% in clinical trials 5
• Patients must abstain from sexual intercourse for 7 days after single-dose therapy or until completion of 7-day regimen 2, 4

Additional Alternatives:

• Levofloxacin 500 mg orally once daily for 7 days 3, 4, 5
• Ofloxacin 300 mg orally twice daily for 7 days 2, 4, 5
• Erythromycin base 500 mg orally four times daily for 7 days (less effective, more GI side effects) 2, 4, 5

Important Caveats:

• Test-of-cure for rectal chlamydia if treated with azithromycin 1
• Rescreen all women approximately 3 months after treatment due to high reinfection rates 4, 5
• Coinfection with gonorrhea is common; treat presumptively for both when gonorrhea is diagnosed 2, 6

Gonorrhea (Neisseria gonorrhoeae)

Recommended First-Line Treatment:

• Ceftriaxone 500 mg IM as a single dose for patients weighing ≥150 kg 1
• Ceftriaxone 250 mg IM as a single dose for patients weighing <150 kg 1
• PLUS treatment for chlamydia (doxycycline 100 mg orally twice daily for 7 days) due to high coinfection rates 7, 1

Key Clinical Points:

• Ceftriaxone monotherapy is now recommended (no longer requires dual therapy with azithromycin) 1
• Weight-based dosing reflects updated 2021 CDC guidelines 1
• Increasing antimicrobial resistance limits oral treatment options 8, 9

Pharyngeal Gonorrhea:

• Same ceftriaxone dosing as above 2
• Test-of-cure is mandatory for all pharyngeal gonorrhea cases 1
• Pharyngeal infections are more difficult to eradicate than urogenital infections 2

Alternative Regimens (if ceftriaxone unavailable):

• Cefixime 800 mg orally as a single dose (less effective than ceftriaxone) 2
• Spectinomycin 2 g IM (not available in US; useful for cephalosporin allergy; ineffective for pharyngeal infection) 2

Critical Management Points:

• Patients should abstain from sexual intercourse until therapy completed and partners treated 2
• Partner notification and treatment within 60 days of symptom onset 2
• Fluoroquinolones (ciprofloxacin, ofloxacin) are no longer recommended due to widespread resistance 2, 8

Syphilis (Treponema pallidum)

Primary, Secondary, or Early Latent Syphilis (<1 year duration):

• Penicillin G benzathine 2.4 million units IM as a single dose 1

Late Latent Syphilis or Unknown Duration (>1 year):

• Penicillin G benzathine 2.4 million units IM weekly for 3 consecutive weeks 1

Neurosyphilis, Ocular, or Otic Syphilis:

• Aqueous crystalline penicillin G 18-24 million units IV daily (administered as 3-4 million units IV every 4 hours or continuous infusion) for 10-14 days 1

Key Clinical Points:

• Penicillin remains the only proven effective treatment for syphilis 9
• Thorough evaluation for neurologic, ophthalmic, and otic symptoms is essential at any stage 1
• These complications can occur at any stage and require IV penicillin therapy 1

Screening Recommendations:

• Screen all pregnant women three times: first prenatal visit, third trimester, and at delivery 10
• Screen persons living in counties with primary/secondary syphilis rates >4.6 per 100,000 (Healthy People 2030 threshold) 10

Penicillin Allergy:

• Desensitization is required for pregnant women 3
• Alternative regimens exist for non-pregnant patients but are less well-studied 3

Trichomoniasis (Trichomonas vaginalis)

Recommended First-Line Treatment:

• Metronidazole 500 mg orally twice daily for 7 days 1
• Alternative: Metronidazole 2 g orally as a single dose 7
• Alternative: Tinidazole 2 g orally as a single dose 7

Key Clinical Points:

• The 7-day metronidazole regimen is now preferred over single-dose therapy 1
• Approximately 70% of trichomoniasis infections are asymptomatic 8
• Patients should abstain from alcohol during treatment and for 24 hours after metronidazole or 72 hours after tinidazole 7

Important Management:

• Treat sexual partners simultaneously 7
• If alcohol recently ingested or emergency contraception provided, can take medication at home rather than directly observed 7

Genital Herpes (HSV-1 and HSV-2)

First Clinical Episode:

• Acyclovir 400 mg orally three times daily for 7-10 days 11
• Valacyclovir 1 g orally twice daily for 7-10 days 11
• Famciclovir 250 mg orally three times daily for 7-10 days 11

Recurrent Episodes:

• Acyclovir 800 mg orally twice daily for 5 days 11
• Valacyclovir 500 mg orally twice daily for 3 days 11
• Famciclovir 1 g orally twice daily for 1 day 11

Suppressive Therapy (for frequent recurrences):

• Acyclovir 400 mg orally twice daily 11
• Valacyclovir 500-1000 mg orally once daily 11
• Famciclovir 250 mg orally twice daily 11

Key Clinical Points:

• No cure is available for genital herpes 8
• Early initiation of therapy reduces duration of illness and may prevent complications including urinary retention, meningism, or severe systemic illness 11
• Rates of HSV-1 and HSV-2 have declined in the US from 1999-2016 8
• Nucleic acid amplification tests have high sensitivity (86.1-100%) and specificity (97.1-100%) for symptomatic HSV 8

Genital Warts (HPV types 6 and 11)

Patient-Applied Treatments:

• Imiquimod 5% cream applied once daily at bedtime, three times per week for up to 16 weeks 12
• Podofilox 0.5% solution or gel applied twice daily for 3 days, followed by 4 days off therapy, repeated for up to 4 cycles 12
• Sinecatechins 15% ointment (green tea extract catechins) applied three times daily for up to 16 weeks 12

Provider-Applied Treatments:

• Cryotherapy with liquid nitrogen or cryoprobe, repeated every 1-2 weeks 2
• Podophyllin resin 10-25% in compound tincture of benzoin, applied weekly 2
• Trichloroacetic acid (TCA) 80-90% applied weekly 2
• Surgical removal (excision, electrocautery, laser) 2

Key Clinical Points:

• Sinecatechins is a newer patient-applied option added to 2010 CDC guidelines 12
• No single treatment is ideal for all patients or all warts 2
• Visible genital warts are usually caused by HPV types 6 or 11, which are not associated with cervical cancer 2
• HPV vaccine (quadrivalent or bivalent) is recommended for prevention 12

Mycoplasma genitalium

Recommended Treatment:

• Moxifloxacin 400 mg orally once daily for 7-14 days 9, 10
• Alternative: Doxycycline 100 mg orally twice daily for 7 days followed by moxifloxacin 400 mg orally once daily for 7 days 10

Key Clinical Points:

• High resistance to macrolides (azithromycin) limits treatment options 8, 9
• Fluoroquinolones like moxifloxacin are increasingly required 8, 9
• Testing and treatment guidance continues to evolve 10

Sexual Assault Prophylaxis

Recommended Empiric Regimen:

• Ceftriaxone 250 mg IM single dose PLUS Azithromycin 1 g orally single dose PLUS Metronidazole 2 g orally single dose (or Tinidazole 2 g orally single dose) 7
• Emergency contraception should be considered 7
• Hepatitis B vaccination if not previously vaccinated 7
• HPV vaccination for females aged 9-26 years and males aged 9-21 years (through age 26 for MSM) 7

Rationale:

• Compliance with follow-up is poor among sexual assault survivors 7
• Presumptive treatment covers chlamydia, gonorrhea, and trichomoniasis 7
• If alcohol recently ingested, metronidazole/tinidazole can be taken at home to minimize side effects 7