Pediatric Syphilis Treatment & Management

Updated: Dec 12, 2022
  • Author: Muhammad Waseem, MBBS, MS, FAAP, FACEP, FAHA; Chief Editor: Russell W Steele, MD  more...
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Approach Considerations

Penicillin remains the drug of choice to treat all stages of syphilis; no evidence suggests an increasing penicillin resistance. Primary, secondary, and early latent diseases are treated with a single intramuscular (IM) dose of benzathine penicillin G (50,000 U/kg; not to exceed 2.4 million U).

In patients with primary syphilis, doxycycline and tetracycline have shown a high serological treatment success rate, comparable to penicillin. [17] Azithromycin has also demonstrated a high cure rate in a long-term follow-up. [18]

Patients who are allergic to penicillin and do not have neurosyphilis and are not pregnant may be treated with either doxycycline (100 mg oral [PO] bid for 2 wk) or tetracycline (500 mg PO qid for 2 wk).

Although other regimens can be considered in patients with a penicillin allergy, desensitization to penicillin is the most advisable approach.

Serologic testing after treatment is important for all patients with syphilis, particularly those co-infected with HIV.

Go to Syphilis for more complete information on this topic.


Treatment of Neurosyphilis

Shorter-acting forms of penicillin must be used to treat neurosyphilis to produce reliably therapeutic levels in the cerebrospinal fluid (CSF). The recommended treatment is aqueous crystalline penicillin G (200,000-300,000 U/kg/d IM [50,000 U/kg every 4-6 h]) for 10-14 days (adult dose, 12-24 million U/d [2-4 million U every 4 h]), followed by a single dose of benzathine penicillin (50,000 U/kg/dose, not to exceed 2.4 million U) in 3 weekly doses.

Indications for CSF examination prior to initiating treatment of syphilis include the following:

  • Evidence of neurosyphilis

  • Evidence of tertiary syphilis (eg, aortitis, gumma, iritis)

  • Treatment failure

  • Patients with HIV infection with late latent syphilis or syphilis of unknown duration

  • Rapid plasma reagin (RPR) test result exceeding 1:32 (unless syphilis duration < 1 y)

CSF interpretation is difficult in newborns because the normal values for CSF cell count and protein concentration widely vary. In addition, a negative CSF Venereal Disease Research Laboratory (VDRL) test result cannot exclude neurosyphilis. Conversely, the CSF VDRL test result can be positive in an uninfected newborn with a transplacentally acquired high serum VDRL finding. Thus, all infants suspected of having congenital syphilis should be treated for neurosyphilis.

When distribution shortages of aqueous penicillin G occur, substitution of ampicillin or ceftriaxone may be necessary (see the CDC Web page "Alternatives to intravenous penicillin G for specific infections" for the most up-to-date recommendations).

Go to Neurosyphilis for more complete information on this topic.


Congenital Syphilis in Newborns

Treat congenital infection, either proven or presumed, with 10-14 days of aqueous penicillin G or procaine penicillin G. Aqueous crystalline penicillin G is recommended if congenital syphilis is proved or is highly suspected. Base dosage on chronologic, not gestational, age.

The recommended dosage is 100,000-150,000 U/kg/d IV every 8-12 hours to complete a 10-day to 14-day course. Procaine penicillin G (50,000 U/kg IM) has been recommended as an alternative to treat congenital syphilis, but adequate CSF concentration may not be consistently achieved. Infection is suspected with the following:

  • Physical or radiographic evidence of active disease

  • Serum quantitative nontreponemal titer at least 4 times greater than the maternal titer

  • Reactive CSF VDRL test result or abnormal CSF cell count and/or protein levels

  • Positive immunoglobulin M (IgM) fluorescent treponemal antibody absorption (FTA-ABS) test findings

  • Positive darkfield microscopy findings or positive findings when staining for treponemes in placenta or umbilical cord


Congenital Syphilis in Older Infants and Children

Treat diagnosed infants older than 4 weeks with aqueous crystalline penicillin (200,000-300,000 U/kg/d IV divided every 6 h for 10-14 d).


Syphilis in Pregnancy

Treat all pregnant patients with syphilis with penicillin, regardless of the stage of pregnancy. [19, 20] Administer 3 doses of benzathine penicillin (2.4 million U IM at 1-wk intervals). A meta-analysis regarding penicillin use in pregnancy has shown that the dose of 2.4 million IU results in reduction of clinical congenital syphilis by 97%, whereas same dose is associated with a reduction of 82% of stillbirths, 64% of preterm deliveries, and 80% of neonatal death.

No proven alternative therapy is available for patients who are allergic to penicillin. Erythromycin treatment for pregnant patients who are allergic to penicillin is not a reliable treatment for the fetus.

If the patient has a penicillin allergy that is confirmed by the demonstration of an immediate wheal-and-flare response to skin testing with penicilloyl-polylysine or penicillin G minor determinant mixture, desensitization and penicillin treatment should be performed in a hospital, following the guidelines issued by the Centers for Disease Control and Prevention.

Pregnant females who are allergic to penicillin should be desensitized and then treated with penicillin G. It also may be helpful to perform skin testing or use an oral graded penicillin dose challenge in order to identify females at risk for acute allergic reactions. [21]


Early Acquired Syphilis

For primary, secondary, or latent syphilis that is less than a year's duration, a single dose of IM benzathine penicillin G in a total dose of 50,000 U/kg (not to exceed 2.4 million U) is the recommended treatment. Exclude neurosyphilis by CSF examination in all pediatric patients.

Late Syphilis

For syphilis of longer than 1 year in duration, the recommended treatment is benzathine penicillin G, 50,000 U/kg IM (not to exceed 2.4 million U) weekly for 3 successive weeks.


Syphilis in HIV-Infected Persons

Treatment of co-infected individuals may require high-dose or prolonged therapy.

Some authorities, persuaded by reports of the persistence of T pallidum in the cerebrospinal fluid (CSF) of persons infected by HIV after standard penicillin benzathine therapy for early syphilis, now recommend CSF examination of all co-infected patients for neurosyphilis, regardless of the clinical stage of syphilis. These authorities treat for neurosyphilis when no CSF examination is performed or when examination reveals CSF abnormalities.

Persistent infection

The question of persistent infection despite adequate therapy has been controversial. Sequestration of spirochetes has been reported in such sites as the anterior chamber of the eye, the CNS, and the labyrinth of the inner ear. CSF parameters are expected to normalize within 2 years. Failure to normalize may warrant retreatment.

Anyone with neurologic, optic, or otic abnormalities who has syphilis or has a history of syphilis (current or untreated) should be considered for CSF examination and should be treated for neurosyphilis.



The Jarisch-Herxheimer reaction is the major complication of therapy and occurs in 50% of patients with primary syphilis, in 90% of those with secondary syphilis, and in 25% of those with early latent syphilis. It was first described in patients with syphilis by Jarisch in 1895 and then Herxheimer in 1902. The reaction, which is self-limited, is associated with an increase in circulating levels of tumor necrosis factor, interleukin (IL)-6, and IL-8.

Onset begins within 2 hours of treatment initiation and consists of the abrupt onset of fever, chills, myalgias, headache, tachycardia, hyperventilation, vasodilation with flushing, and mild hypotension. The temperature peaks at about 7 hours, and defervescence takes place within 12-24 hours.

Warn pregnant patients about the risk of a Jarisch-Herxheimer reaction. This reaction may be associated with mild premature contractions but rarely results in premature delivery.



Although rates of early syphilis are declining, maintaining a high index of suspicion about at-risk patients is important. Indications for syphilis screening include the following: [22]

  • Exposure to a known case of infectious syphilis

  • All women at first prenatal visit and high-risk women again at 28 weeks' gestation (46 states and the District of Columbia have laws regarding antenatal syphilis screening during pregnancy and at delivery) - A recent study showed a 50% reduction in stillbirth rates with early screening and treatment in pregnancy

  • All women that deliver a stillborn infant

  • All newborns older than 22 weeks' gestation whose mothers were not screened

  • Anyone diagnosed with a sexually transmitted disease (STD) or anyone presenting for STD evaluation

  • Any person who tests positive for HIV

  • Anyone engaging in high-risk behaviors (eg, drug use, prostitution, unprotected sex)

For health care personnel, standard precautions are recommended for all patients with primary and secondary syphilis because these lesions are moist and potentially infectious. Drainage and secretion precautions are necessary for all patients who have suspected or proven syphilis until therapy has been administered for at least 24 hours.

Trace and contact all sexual partners of infected patients

All persons (including health care providers) who have had close, unprotected contact with early congenital syphilis before identification of the disease or during the first 24 hours of therapy should be examined clinically for the presence of lesions 2-3 weeks after contact. Serologic testing should be performed and repeated 3 months after contact or earlier if symptoms occur. Consider immediate treatment if the degree of exposure may have been significant.

Consider STD prophylaxis for rape victims. Many people who are sexually assaulted do not comply with recommended follow-up, so consider empiric therapy for these patients.



Given the protean manifestations of syphilis, consultation with a range of specialists may be valuable, such as the following

  • Consultation with an infectious disease specialist is useful in most cases.

  • Consultation with a neurologist is prudent if neurosyphilis is present or suspected

  • Consultation with an ophthalmologist is helpful because keratitis and optic atrophy are common; slit lamp examination and follow-up are important.

  • An orthopedist can provide support for skeletal gummas, which most often involve the legs; bony involvement in congenital syphilis frequently resolves in the first 6 months, but lesions may be painful until healed.

  • Otolaryngology consultation may be required because congenital syphilis is a known cause of progressive sensorineural hearing loss; therefore, hearing screening is recommended for all pediatric patients with congenital syphilis. [23]


Long-Term Monitoring

Congenital syphilis requires follow-up at age 1 month, 2 months, 4 months, 6 months, and 12 months. Obtain nontreponemal titers at age 3 months, 6 months, and 12 months after conclusion of treatment. Nontreponemal antibody titers should decline by age 3 months and should be nonreactive by age 6 months. Consider re-treatment for patients with persistently stable titers, including low titers.

Infants who are treated for congenital neurosyphilis should undergo repeat clinical evaluation and CSF examination at 6-month intervals until their CSF examination result is normal. A positive CSF Venereal Disease Research Laboratory (VDRL) result at age 6 months is an indication for retreatment.

Early acquired syphilis requires follow-up with a quantitative nontreponemal test at 3-month, 6-month, and 12-month intervals after conclusion of treatment. Patients with syphilis for more than one year also should undergo serologic testing 24 months after treatment. Pregnant patients who have received treatment should have quantitative serologic testing monthly for the remainder of their pregnancy. [10]