What is the recommended dose of benzathine penicillin (Bicillin) for treating syphilis?

Benzathine Penicillin Dosing for Syphilis

For early syphilis (primary, secondary, or early latent), administer benzathine penicillin G 2.4 million units intramuscularly as a single dose; for late latent syphilis or syphilis of unknown duration, administer 7.2 million units total as three weekly doses of 2.4 million units each. 1, 2

Adult Dosing by Stage

Early Syphilis (Primary, Secondary, Early Latent)

• Single dose of 2.4 million units IM is the standard treatment 2, 1
• Recent high-quality evidence confirms that one dose is noninferior to three doses, with 76% serologic response at 6 months in both regimens 3
• This single-dose regimen achieves 90-100% treatment success rates 4
• Administration should be deep intramuscular in the upper outer quadrant of the buttock (dorsogluteal) or ventrogluteal site 1

Late Latent Syphilis or Unknown Duration

• Total of 7.2 million units administered as three separate doses of 2.4 million units IM at weekly intervals 2, 1
• Each injection must be spaced exactly 7 days apart 2
• If a dose is missed, pharmacologic considerations suggest a 10-14 day interval may be acceptable before restarting the sequence, though this is not well-established 2

Neurosyphilis

• Requires intravenous therapy, not intramuscular benzathine penicillin 5
• Aqueous crystalline penicillin G 18-24 million units daily (3-4 million units IV every 4 hours) for 10-14 days 5

Pediatric Dosing

Children with Acquired Syphilis (≥1 month old)

• 50,000 units/kg IM, up to the adult dose of 2.4 million units for early syphilis as a single dose 2
• For late latent syphilis: 50,000 units/kg IM administered as three doses at weekly intervals (total 150,000 units/kg up to 7.2 million units) 2
• All children require CSF examination to exclude neurosyphilis before treatment 2

Congenital Syphilis

• Infants under 2 years: 50,000 units/kg body weight 1
• Ages 2-12 years: adjust based on adult dosage schedule 1
• Treatment regimens vary significantly based on maternal treatment history and infant evaluation findings 2

Special Populations

HIV-Infected Patients

• Use the same single-dose regimen (2.4 million units IM) for early syphilis 2
• A 2025 randomized trial demonstrated that single-dose therapy was noninferior to three-dose therapy in HIV-infected individuals, with 76% serologic response in the single-dose group versus 71% in the three-dose group 3
• Earlier 2017 data showed 93% success with single dose versus 100% with three doses in per-protocol analysis, supporting single-dose treatment 6
• Additional doses do not enhance efficacy regardless of HIV status 2
• More frequent serologic follow-up (every 3 months) is recommended 7

Pregnant Women

• Same stage-appropriate penicillin dosing as non-pregnant adults 8, 5
• For primary, secondary, or early latent: 2.4 million units IM single dose 8
• Some specialists recommend a second dose of 2.4 million units IM one week later, especially in third trimester or with secondary syphilis 8
• For late latent or unknown duration: 7.2 million units total as three weekly doses of 2.4 million units 8
• Penicillin is the only proven effective treatment to prevent mother-to-fetal transmission 8
• Women with penicillin allergy must undergo desensitization and then receive penicillin—no alternatives are acceptable 8
• If any dose is missed, the entire course must be repeated 2

Follow-Up and Treatment Response

Serologic Monitoring

• For early syphilis: clinical and serologic evaluation at 6 and 12 months 2
• For latent syphilis: repeat quantitative nontreponemal tests at 6,12, and 24 months 2
• A fourfold decline in titer (two dilutions) is expected within 6 months for primary/secondary syphilis 5
• Serologic response is generally slower (12-24 months) for latent syphilis 4

Treatment Failure Criteria

• Titers increase fourfold after initial decline 2
• Initially high titer (>1:32) fails to decline at least fourfold within 12-24 months 2
• Signs or symptoms attributable to syphilis develop 2
• For treatment failure: administer benzathine penicillin G 2.4 million units IM weekly for 3 weeks, unless CSF examination indicates neurosyphilis 2

Critical Pitfalls to Avoid

• Never use tetracyclines, doxycycline, or erythromycin in pregnant women—these do not prevent congenital syphilis 8
• Do not inject benzathine penicillin intravenously, into or near an artery or nerve, or admix with other IV solutions 1
• Avoid administration in the anterolateral thigh due to adverse effects; use dorsogluteal or ventrogluteal sites instead 1
• Do not assume that persistent low-titer reactivity (serofast state) necessarily indicates treatment failure—a significant proportion of patients remain seropositive despite adequate treatment 7, 4
• Never compare titers between different test types (VDRL vs RPR) as they are not directly comparable 7
• Inject at a slow, steady rate to prevent needle blockage due to high concentration of suspended material 1