Is penicillin recommended for prophylaxis against male Sexually Transmitted Infections (STIs)?

Penicillin is NOT Recommended for STI Prophylaxis in Males

Penicillin has no role in prophylaxis against sexually transmitted infections; the only antibiotic currently recommended for STI prophylaxis is doxycycline post-exposure prophylaxis (doxy PEP) at 200 mg within 72 hours after sexual contact, and this is specifically indicated only for gay, bisexual, and other men who have sex with men (MSM) and transgender women with a history of bacterial STI in the past 12 months. 1, 2

Current Evidence-Based Prophylaxis Strategy

Doxycycline PEP is the Only Recommended Prophylaxis

• The CDC 2024 guidelines establish doxy PEP (200 mg taken within 72 hours after sexual contact) as the sole recommended antibiotic prophylaxis for preventing bacterial STIs 1, 2
• This regimen reduces syphilis and chlamydia infections by >70% and gonococcal infections by approximately 50% 2, 3
• Maximum dosing is 200 mg every 24 hours 4

Specific Target Population

• Doxy PEP should be offered to MSM and transgender women who have had at least one bacterial STI (syphilis, chlamydia, or gonorrhea) diagnosed in the past 12 months 1, 2
• Using shared decision-making, it may be discussed with MSM and transgender women without recent STI diagnosis but engaging in high-risk sexual activities 1

Why Penicillin is Not Used for Prophylaxis

Penicillin's Role is Limited to Treatment

• Penicillin (specifically benzathine penicillin G) remains the gold standard for treating established syphilis, not preventing it 5
• Penicillin is used as an alternative treatment option for syphilis in non-pregnant patients with penicillin allergy (using doxycycline instead) 3, 4

Resistance Patterns Preclude Prophylactic Use

• Widespread plasmid-mediated resistance to penicillins in Neisseria gonorrhoeae and Haemophilus ducreyi has eliminated penicillin as a viable option for gonorrhea prevention or treatment 6
• Chromosomally mediated antimicrobial resistance further limits penicillin's therapeutic utility 6

Clinical Implementation Algorithm

For MSM and transgender women presenting for STI prevention counseling:

1. Assess eligibility criteria:

   • History of bacterial STI (syphilis, chlamydia, or gonorrhea) in past 12 months? → Strongly recommend doxy PEP 1, 2
   • No recent STI but high-risk sexual behavior? → Discuss doxy PEP using shared decision-making 1

2. Prescribe doxy PEP if appropriate:

   • Dosing: 200 mg within 72 hours after oral, vaginal, or anal sexual contact 2, 4
   • Counsel on photosensitivity, gastrointestinal symptoms, and esophageal irritation risks 3, 4

3. Maintain comprehensive STI screening:

   • Baseline screening before initiating doxy PEP 4
   • Ongoing screening every 3-6 months 4

Important Caveats

Limitations of Doxy PEP Coverage

• Doxy PEP does not prevent Mycoplasma genitalium infections 2, 3
• Regular STI screening remains essential as doxy PEP does not provide comprehensive protection against all STIs 2

Antimicrobial Resistance Concerns

• Approximately 9% of HIV PrEP users report self-prescribed antibiotic STI prophylaxis, which is not recommended and raises antimicrobial resistance concerns 7
• Clinicians should specifically ask about unsanctioned antibiotic use for STI prevention to provide appropriate counseling 7

Contraindications to Doxycycline

• Pregnancy, children under 8 years of age, and severe liver dysfunction are absolute contraindications 3, 4

The evidence unequivocally supports doxycycline PEP as the only recommended prophylactic antibiotic strategy for bacterial STIs, with penicillin reserved exclusively for treatment of established infections. 1, 2, 3