What is the recommended dosing for acute syphilis treatment with benzathine penicillin G (Bicillin)?

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From the Guidelines

The recommended treatment for acute syphilis is a single intramuscular injection of benzathine penicillin G (Bicillin L-A) at a dose of 2.4 million units, administered as two separate 1.2 million unit injections, one in each buttock, due to the volume of medication, as supported by the most recent and highest quality study 1. This regimen is highly effective because the long-acting formulation maintains treponemicidal levels in the blood for 2-3 weeks, which is sufficient to eliminate Treponema pallidum, the causative organism of syphilis. Some key points to consider when treating acute syphilis include:

  • Patients should be advised that they may experience a Jarisch-Herxheimer reaction within 24 hours of treatment, characterized by fever, headache, myalgia, and worsening of syphilitic lesions due to the release of bacterial products as organisms die.
  • Sexual partners from the past 90 days should be evaluated and treated presumptively, and patients should abstain from sexual contact until treatment is complete and lesions have healed.
  • For patients with penicillin allergy, doxycycline 100 mg orally twice daily for 14 days is an alternative, though penicillin remains the preferred treatment, especially for pregnant women, for whom desensitization may be necessary, as noted in 1. It's also important to note that while other alternatives like azithromycin and ceftriaxone may be considered in certain cases, their use should be approached with caution due to concerns about resistance and limited data on their efficacy in treating syphilis, as discussed in 1.

From the Research

Recommended Dosing for Acute Syphilis

  • The recommended dosing for acute syphilis treatment with benzathine penicillin G (Bicillin) is a single dose of 2.4 million units administered intramuscularly 2, 3, 4.
  • This dosing regimen is effective for treating early syphilis, including primary, secondary, and early latent syphilis 2, 3.
  • For patients coinfected with HIV, a single dose of 2.4 million units of benzathine penicillin G is still recommended, as a 3-dose regimen did not improve syphilis serological outcomes 4.

Alternative Treatment Options

  • Azithromycin has been studied as an alternative treatment option for syphilis, with some studies showing promising results 2, 5.
  • However, the emergence of azithromycin-resistant Treponema pallidum has limited its use as a routine treatment option 3, 6.

Treatment Outcomes

  • Treatment success is defined as a decrease in rapid plasma reagin (RPR) titers of ≥2 dilutions (4-fold) during a 12-month follow-up period 4.
  • CD4 T-cell count, RPR titer, and syphilis stage do not affect treatment results 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Management of adult syphilis.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2011

Research

Single Dose Versus 3 Doses of Intramuscular Benzathine Penicillin for Early Syphilis in HIV: A Randomized Clinical Trial.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2017

Research

Syphilis: antibiotic treatment and resistance.

Epidemiology and infection, 2015

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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