Is Augmentin (amoxicillin/clavulanate) effective in treating syphilis with a low Rapid Plasma Reagin (RPR) titer?

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Last updated: April 29, 2025 • View editorial policy

From the Guidelines

Augmentin (amoxicillin-clavulanate) is not adequate treatment for syphilis, even with a low RPR titer, and should not be used as a substitute for the recommended penicillin G treatment. The recommended treatment for syphilis is penicillin G, specifically benzathine penicillin G 2.4 million units administered intramuscularly as a single dose for primary, secondary, or early latent syphilis (less than one year duration) 1. For late latent syphilis or syphilis of unknown duration, the recommended regimen is benzathine penicillin G 2.4 million units intramuscularly once weekly for three weeks. While Augmentin contains amoxicillin (a penicillin derivative), it does not achieve the sustained blood levels necessary to effectively treat Treponema pallidum, the bacterium causing syphilis.

Some key points to consider in the treatment of syphilis include:

  • A low RPR titer might indicate early infection, previously treated infection, or partial treatment, but proper treatment is still required 2.
  • If penicillin allergy is a concern, doxycycline 100 mg orally twice daily for 14 days (primary, secondary, early latent) or 28 days (late latent) can be used as an alternative 1.
  • Partial treatment can lead to treatment failure, progression of disease, and complications including neurosyphilis, cardiovascular syphilis, or congenital transmission during pregnancy.
  • Follow-up serologic testing is essential to confirm treatment success, typically at 6 and 12 months after treatment.

It's also important to note that other alternatives, such as ceftriaxone (intravenous or intramuscular; 1 g/d for 10 days), may be considered in certain cases, but the use of azithromycin is not recommended due to concerns about resistance and treatment failures 1.

From the Research

Treatment of Syphilis with Augmentin

  • There is no direct evidence to support the use of Augmentin (amoxicillin-clavulanate) as a treatment for syphilis, particularly in cases with low RPR titer 3, 4, 5.
  • The recommended treatment for syphilis is benzathine penicillin G, with a single dose of 2.4 million units being the standard for early syphilis 3, 5.
  • Alternative treatments, such as azithromycin, have been studied, but their efficacy is uncertain due to concerns about resistance 4, 6.
  • A study on the use of amoxicillin (1.5 g/day) without probenecid for the treatment of syphilis showed promising results, with a serological cure rate of 94.9% 7.
  • However, it is essential to note that Augmentin is not mentioned in the studies as a treatment option for syphilis, and its use in this context is not supported by the available evidence.

RPR Titer and Treatment Response

  • A low RPR titer may indicate partial treatment of syphilis, but it is not a reliable indicator of treatment success 3, 5.
  • The Centers for Disease Control and Prevention (CDC) recommend that patients with syphilis be monitored for serologic response to treatment, with a ≥4-fold decline in RPR titers expected within 6-12 months for early syphilis and 12-24 months for latent syphilis 3, 5.
  • Patients with low RPR titers who do not achieve a ≥4-fold decline in titers after treatment may require further evaluation, including cerebrospinal fluid (CSF) examination, to rule out neurosyphilis 3.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

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

Syphilis: antibiotic treatment and resistance.

Epidemiology and infection, 2015

Research

Azithromycin versus penicillin G benzathine for early syphilis.

The Cochrane database of systematic reviews, 2012

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.