What is the dosage of benzathine penicillin G (Bicillin) for late latent syphilis?

Treatment of Late Latent Syphilis with Benzathine Penicillin G

For late latent syphilis, administer benzathine penicillin G 7.2 million units total as three separate intramuscular injections of 2.4 million units each, spaced exactly one week apart. 1, 2, 3

Dosing Regimen

• Each dose consists of 2.4 million units administered intramuscularly 1, 2
• The three injections must be given at weekly intervals (7 days apart) 1, 4
• Total cumulative dose is 7.2 million units over three weeks 1, 2, 5

Administration Technique

• Inject deep intramuscularly in the upper outer quadrant of the buttock (dorsogluteal) or ventrogluteal site 3
• Inject slowly and steadily to prevent needle blockage due to high concentration of suspended material 3
• Vary the injection site with each repeated dose 3
• Never administer intravenously, into or near an artery or nerve 3

Critical Pre-Treatment Evaluation

Before initiating treatment, perform the following assessments:

• CSF examination is indicated if the patient has neurologic or ophthalmic symptoms, evidence of tertiary syphilis, treatment failure history, HIV infection with late latent syphilis, or nontreponemal titer ≥1:32 1, 2
• If CSF shows abnormalities consistent with neurosyphilis, switch to aqueous crystalline penicillin G 18-24 million units IV daily for 10-14 days instead 1, 2
• Test all patients for HIV infection 1, 2
• Examine all accessible mucosal surfaces (oral cavity, perineum, under foreskin) to exclude active lesions that would indicate earlier stage disease 1

Missed Dose Management

• If a dose is missed, an interval of 10-14 days between doses may be acceptable before restarting the sequence 1, 2
• For pregnant women, any missed dose requires restarting the entire three-dose course 1

Pediatric Dosing

• Children with late latent syphilis: 50,000 units/kg IM (up to adult dose of 2.4 million units) for three doses at weekly intervals 1, 2
• Total pediatric dose: 150,000 units/kg up to adult total of 7.2 million units 1, 2
• All children require CSF examination before treatment to exclude neurosyphilis 1, 4

Penicillin Allergy Alternatives (Non-Pregnant Adults Only)

• Doxycycline 100 mg orally twice daily for 28 days 1, 2
• Tetracycline 500 mg orally four times daily for 28 days 1
• These alternatives have limited efficacy data and require close serologic and clinical follow-up 1
• Pregnant women with penicillin allergy must undergo desensitization followed by penicillin treatment—no substitutes are acceptable 2, 5, 4

Follow-Up Monitoring

• Repeat quantitative nontreponemal tests (RPR or VDRL) at 6,12, and 24 months 1, 2
• Expected response: fourfold decline in titer within 12-24 months 2, 5
• Re-treat if titers increase fourfold, initially high titer (≥1:32) fails to decline fourfold within 12-24 months, or signs/symptoms develop 1
• Use the same test type (RPR or VDRL) throughout follow-up—results are not directly comparable between different test methods 2

Special Population Considerations

HIV-Infected Patients

• Same three-dose regimen as HIV-negative patients 2, 4
• Closer follow-up is mandatory to detect treatment failure 2
• Limited data suggest no benefit to additional doses beyond the standard three-dose regimen 2

Pregnant Women

• Penicillin is the only proven effective therapy to prevent congenital syphilis 2, 5, 4
• Screen all pregnant women at first prenatal visit, during third trimester, and at delivery 2
• Jarisch-Herxheimer reaction during second half of pregnancy may precipitate premature labor or fetal distress 2
• Women should seek immediate medical attention for changes in fetal movements or contractions after treatment 2

Common Pitfalls to Avoid

• Never use benzathine penicillin G for neurosyphilis—it does not achieve adequate CSF levels 2, 5
• Do not use oral penicillin preparations—they are ineffective for syphilis treatment 2
• Do not rely on treponemal antibody titers to assess treatment response—they correlate poorly with disease activity 2
• Do not use tetracyclines, doxycycline, or erythromycin in pregnant women—they do not prevent congenital syphilis 4
• Avoid azithromycin due to widespread macrolide resistance and documented treatment failures 2

Expected Adverse Effects

• Most patients experience local injection-site pain and tenderness (76-85% of patients) 6
• Jarisch-Herxheimer reaction may occur within 24 hours, presenting with fever, headache, and myalgia, especially in early syphilis 2