Syphilis | Questions & Answers | 2015 STD Treatment Guidelines

Question: What is the minimum treatment interval for administering benzathine penicillin in late latent syphilis in pregnant and non pregnant persons?

No data exist which directly address the question about minimum treatment interval for administering benzathine penicillin G to treat late latent syphilis in pregnant and non pregnant persons.  Ideally, patients will receive their second and third weekly injections exactly seven days after the prior injection.  However, a treatment interval of five or six days between injections in non pregnant persons may be adequate (with five days being the minimum treatment interval).  Treatment of late latent syphilis requires sustained levels of penicillin within the body, and giving a second or third weekly injection too soon might inappropriately shorten the total duration of penicillin within the body at the end of treatment.  Similarly, giving a follow-up injection too late (more than nine days after the prior injection) risks allowing the penicillin level within the body to fall too low, and could theoretically facilitate treatment failure.  The recommended regimen for pregnant and non-pregnant adults with late latent syphilis or syphilis of unknown duration is benzathine penicillin G 7.2 million units total, administered as 3 doses of 2.4 million units IM each at 1-week intervals. Pharmacologic data suggest that giving subsequent doses of benzathine penicillin G as close as possible to 7 days following the previous dose is the safest approach to ensure consistent blood levels.

Question: After treatment for neurosyphilis, should a person receive 2.4 MU of benzathine penicillin weekly for three weeks?

Additional intramuscularly administered benzathine penicillin once per week for up to three weeks after the completion of neurosyphilis treatment can be considered, but this has not been studied extensively.  The rationale for this is because the duration of neurosyphilis treatment is only 10 to 14 days, so giving an additional intramuscularly administered dose of benzathine penicillin at the end of treatment would extend the duration to provide a comparable treatment length for late latent syphilis.  However, there is no published evidence to support this practice, and persons who do not receive additional intramuscular therapy do not seem to have higher rates of treatment failure.  

Question: What is the recommendation for routine neurologic evaluation in asymptomatic syphilis patients?

All patients with syphilis should have a thorough physical examination by an experienced clinician.  This includes an assessment of cognitive function, motor and sensory function, presence of ophthalmic or auditory symptoms, cranial nerve palsy, and symptoms or signs of meningitis or stroke.  If clinical evidence of neurologic involvement is observed, then patients should be referred for cerebrospinal fluid (CSF) examination by lumbar puncture.  Some of these clinical findings may be “soft,” self-reported symptoms (e.g. headaches, blurry vision, hearing loss) and may not be easily validated on physical exam.  Nevertheless, patients reporting any abnormal neurological, ophthalmologic, or audiologic findings in the presence of syphilis infection should be offered CSF examination to evaluate for possible neurosyphilis

Question: What are the indications for CSF examination in syphilis patients with ocular symptoms?

All patients with ocular symptoms (blurred vision, double vision, cranial nerve palsies affecting the eye) should undergo immediate cerebrospinal fluid (CSF) examination, as well as a thorough ophthalmologic examination.  Ocular syphilis is a manifestation of neurosyphilis, which can occur during any stage of syphilis, and may occur even in the absence of CSF abnormalities.  Ocular syphilis is increasingly reported, particularly among HIV-infected men who have sex with men (MSM) (see CDC Clinical Advisory:  Patients with any evidence of ocular involvement, including uveitis, optic neuropathy, retinal vasculitis, or interstitial keratitis, should be managed according to treatment recommendations for neurosyphilis, per CDC guidelines.  CSF examination is recommended before treatment in order to document CSF abnormalities (e.g. CSF-VDRL, cell count, protein).  If CSF abnormalities are present, lumbar puncture should be repeated every six months until the cell count is normal.  If the cell count has not decreased after six months, or if cell count or protein is not normal after two years, then retreatment should be considered.