Congenital syphilis medical therapy
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Kalsang Dolma, M.B.B.S.[2]
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Overview
An afflicted child can be treated using antibiotics much like an adult, however any developmental symptoms are likely to be permanent.
Medical Therapy
If a pregnant mother is identified as being infected with syphilis, treatment can effectively prevent congenital syphilis from developing in the unborn child, especially if she is treated before the sixteenth week of pregnancy. The child is at greatest risk of contracting syphilis when the mother is in the early stages of infection, but the disease can be passed at any point during pregnancy, even during delivery (should the child have not contracted it already). However, a woman in the secondary stage of syphilis decreases her child's risk of developing congenital syphilis by 98% if she receives treatment before the last month of pregnancy. An afflicted child can be treated using antibiotics much like an adult, however any developmental symptoms are likely to be permanent.
2010 Guidelines for Congenital Syphilis by CDC[1]
Scenario 1
Infants with proven or highly probable disease and an abnormal physical examination that is consistent with congenital syphilis, a serum quantitative nontreponemal serologic titer that is fourfold higher than the mother’s titer, or a positive darkfield or fluorescent antibody test of body fluid(s).
Recommended Evaluation
- CSF analysis for VDRL, cell count, and protein
- Complete blood count (CBC) and differential and platelet count
- Other tests as clinically indicated (e.g., long-bone radiographs, chest radiograph, liver function tests, cranial ultrasound, ophthalmologic examination, and auditory brainstem response)
Recommended Regimens
- Aqueous crystalline penicillin G 100,000–150,000 units/kg/day, administered as 50,000 units/kg/dose IV every 12 hours during the first 7 days of life and every 8 hours thereafter for a total of 10 days
Or
- Procaine penicillin G 50,000 units/kg/dose IM in a single daily dose for 10 days
If >1 day of therapy is missed, the entire course should be restarted. Data are insufficient regarding the use of other antimicrobial agents (e.g., ampicillin). When possible, a full 10-day course of penicillin is preferred, even if ampicillin was initially provided for possible sepsis. The use of agents other than penicillin requires close serologic follow-up to assess adequacy of therapy. In all other situations, the maternal history of infection with T. pallidum and treatment for syphilis must be considered when evaluating and treating the infant.
- The absence of a fourfold or greater titer for an infant does not exclude congenital syphilis.
- CSF test results obtained during the neonatal period can be difficult to interpret; normal values differ by gestational age and are higher in preterm infants. Values as high as 25 white blood cells (WBCs)/mm3 and/or protein of 150 mg/dL might occur among normal neonates; some specialists, however, recommend that lower values (i.e., 5 WBCs/mm3 and protein of 40 mg/dL) be considered the upper limits of normal. Other causes of elevated values should be considered when an infant is being evaluated for congenital syphilis.
Scenario 2
Infants who have a normal physical examination and a serum quantitive nontreponemal serologic titer the same or less than fourfold the maternal titer and the mother was not treated, inadequately treated, or has no documentation of having received treatment; mother was treated with erythromycin or other nonpenicillin regimen; or mother received treatment <4 weeks before delivery.
Recommended Evaluation
- CSF analysis for VDRL, cell count, and protein
- CBC and differential and platelet count
- Long-bone radiographs
- A complete evaluation is not necessary if 10 days of parenteral therapy is administered. However, such evaluations might be useful; a lumbar puncture might document CSF abnormalities that would prompt close follow-up. Other tests (e.g., CBC, platelet count, and bone radiographs) may be performed to further support a diagnosis of congenital syphilis. If a single dose of Benzathine penicillin G is used, then the infant must be fully evaluated (i.e., through CSF examination, long-bone radiographs, and CBC with platelets), the full evaluation must be normal, and follow-up must be certain. If any part of the infant’s evaluation is abnormal or not performed or if the CSF analysis is rendered uninterpretable because of contamination with blood, then a 10-day course of penicillin is required.
Recommended Regimens
- Aqueous crystalline penicillin G 100,000–150,000 units/kg/day, administered as 50,000 units/kg/dose IV every 12 hours during the first 7 days of life and every 8 hours thereafter for a total of 10 days
OR
- Procaine penicillin G 50,000 units/kg/dose IM in a single daily dose for 10 days
OR
- Benzathine penicillin G 50,000 units/kg/dose IM in a single dose
Some specialists prefer the 10 days of parenteral therapy if the mother has untreated early syphilis at delivery.
- A woman treated with a regimen other than those recommended in these guidelines for treatment should be considered untreated.
- If the infant’s nontreponemal test is nonreactive and the likelihood of the infant being infected is low, certain specialists recommend no evaluation but treatment of the infant with a single IM dose of benzathine penicillin G 50,000 units/kg for possible incubating syphilis, after which the infant should receive close serologic follow-up.
Scenario 3
Infants who have a normal physical examination and a serum quantitative nontreponemal serologic titer the same or less than fourfold the maternal titer and the mother was treated during pregnancy, treatment was appropriate for the stage of infection, and treatment was administered >4 weeks before delivery; and mother has no evidence of reinfection or relapse.
Recommended Evaluation
No evaluation is required.
Recommended Regimen
- Benzathine penicillin G 50,000 units/kg/dose IM in a single dose
- Some specialists would not treat the infant but would provide close serologic follow-up in those whose mother’s nontreponemal titers decreased fourfold after appropriate therapy for early syphilis or remained stable or low for late syphilis.
Scenario 4
Infants who have a normal physical examination and a serum quantitative nontreponemal serologic titer the same or less than fourfold the maternal titer and the mother’s treatment was adequate before pregnancy, and mother’s nontreponemal serologic titer remained low and stable before and during pregnancy and at delivery (VDRL <1:2; RPR <1:4).
Recommended Evaluation
- No evaluation is required.
Recommended Regimen
- No treatment is required; however, some specialists would treat with benzathine penicillin G 50,000 units/kg as a single IM injection, particularly if follow-up is uncertain.
Special Considerations[1]
Penicillin Allergy
Infants and children who require treatment for syphilis but who have a history of penicillin allergy or develop an allergic reaction presumed secondary to penicillin should be desensitized, if necessary, and then treated with penicillin (see Management of Patients With a History of Penicillin Allergy). Data are insufficient regarding the use of other antimicrobial agents (e.g., ceftriaxone); if a nonpenicillin agent is used, close serologic and CSF follow-up are indicated.
HIV Infection
Evidence is insufficient to determine whether infants who have congenital syphilis and whose mothers are coinfected with HIV require different evaluation, therapy, or follow-up for syphilis than is recommended for all infants.
Penicillin Shortage
During periods when the availability of penicillin is compromised, the following is recommended
For infants with clinical evidence of congenital syphilis (Scenario 1), check local sources for aqueous crystalline penicillin G (potassium or sodium). If IV penicillin G is limited, substitute some or all daily doses with procaine penicillin G (50,000 U/kg/dose IM a day in a single daily dose for 10 days). If aqueous or procaine penicillin G is not available, ceftriaxone (in doses according to age and weight) may be considered with careful clinical and serologic follow-up. Ceftriaxone must be used with caution in infants with jaundice. For infants aged ≥30 days, use 75 mg/kg IV/IM a day in a single daily dose for 10–14 days; however, dose adjustment might be necessary based on birthweight. For older infants, the dose should be 100 mg/kg a day in a single daily dose. Studies that strongly support ceftriaxone for the treatment of congenital syphilis have not been conducted. Therefore, ceftriaxone should be used in consultation with a specialist in the treatment of infants with congenital syphilis. Management may include a repeat CSF examination at age 6 months if the initial examination was abnormal.
For infants at risk for congenital syphilis without any clinical evidence of infection (Scenarios 2 and 3), use procaine penicillin G, 50,000 U/kg/dose IM a day in a single dose for 10 days; OR benzathine penicillin G, 50,000 U/kg IM as a single dose. If any part of the evaluation for congenital syphilis is abnormal, CSF examination is not interpretable, CSF examination was not performed, or follow-up is uncertain, Procaine penicillin G is recommended. A single dose of ceftriaxone is inadequate therapy.
For premature infants at risk for congenital syphilis but who have no other clinical evidence of infection (Scenarios 2 and 3) and who might not tolerate IM injections because of decreased muscle mass, IV ceftriaxone may be considered with careful clinical and serologic follow-up (see Penicillin Shortage, Number 1). Ceftriaxone dosing must be adjusted to age and birthweight.
Follow Up
All seroreactive infants (or infants whose mothers were seroreactive at delivery) should receive careful follow-up examinations and serologic testing (i.e., a nontreponemal test) every 2–3 months until the test becomes nonreactive or the titer has decreased fourfold. Nontreponemal antibody titers should decline by age 3 months and should be nonreactive by age 6 months if the infant was not infected (i.e., if the reactive test result was caused by passive transfer of maternal IgG antibody) or was infected but adequately treated. The serologic response after therapy might be slower for infants treated after the neonatal period. If these titers are stable or increase after age 6–12 months, the child should be evaluated (e.g., given a CSF examination) and treated with a 10-day course of parenteral penicillin G.
Treponemal tests should not be used to evaluate treatment response because the results for an infected child can remain positive despite effective therapy. Passively transferred maternal treponemal antibodies can be present in an infant until age 15 months. A reactive treponemal test after age 18 months is diagnostic of congenital syphilis. If the nontreponemal test is nonreactive at this time, no further evaluation or treatment is necessary. If the nontreponemal test is reactive at age 18 months, the infant should be fully (re)evaluated and treated for congenital syphilis.
Infants whose initial CSF evaluations are abnormal should undergo a repeat lumbar puncture approximately every 6 months until the results are normal. A reactive CSF VDRL test or abnormal CSF indices that cannot be attributed to other ongoing illness requires re-treatment for possible neurosyphilis.
Follow-up of children treated for congenital syphilis after the newborn period should be conducted as is recommended for neonates.
References
- ↑ 1.0 1.1 "CDC - Diseases Characterized by Genital, Anal, or Perianal Ulcers - 2010 STD Treatment Guidelines". Retrieved 2012-12-21.