Which medication is considered first-line therapy for an infant with congenital syphilis

Symptoms and Signs of Congenital Syphilis

Many patients are asymptomatic, and the infection may remain clinically silent throughout their life.

Early congenital syphilis commonly manifests during the first 3 months of life. Manifestations include characteristic vesiculobullous eruptions or a macular, copper-colored rash on the palms and soles and papular lesions around the nose and mouth and in the diaper area, as well as petechial lesions. Generalized lymphadenopathy and hepatosplenomegaly often occur. The infant may fail to thrive and have a characteristic mucopurulent or blood-stained nasal discharge causing snuffles. A few infants develop meningitis, choroiditis, hydrocephalus, or seizures, and others may be intellectually disabled. Within the first 8 months of life, osteochondritis (chondroepiphysitis), especially of the long bones and ribs, may cause pseudoparalysis of the limbs with characteristic radiologic changes in the bones.

Late congenital syphilis typically manifests after 2 years of life and causes gummatous ulcers that tend to involve the nose, septum, and hard palate and periosteal lesions that result in saber shins and bossing of the frontal and parietal bones. Neurosyphilis is usually asymptomatic, but juvenile paresis and tabes may develop. Optic atrophy, sometimes leading to blindness, may occur. Interstitial keratitis Interstitial Keratitis Interstitial keratitis is chronic, nonulcerative inflammation of the mid-stroma (the middle layers of the cornea) that is sometimes associated with uveitis. The cause is usually infectious.... read more

Diagnosis of early congenital syphilis is usually suspected based on maternal serologic testing, which is routinely done early in pregnancy, and often repeated in the 3rd trimester and at delivery. Neonates of mothers with serologic evidence of syphilis should have a thorough examination, darkfield microscopy or immunofluorescent staining of any skin or mucosal lesions, and a quantitative nontreponemal serum test (eg, rapid plasma reagin [RPR], Venereal Disease Research Laboratory [VDRL]); cord blood is not used for serum testing because results are less sensitive and specific. The placenta or umbilical cord should be analyzed using darkfield microscopy or fluorescent antibody staining if available.

Infants and young children with clinical signs of illness or suggestive serologic test results also should have a lumbar puncture with CSF analysis for cell count, VDRL, and protein; complete blood count (CBC) with platelet count; liver tests; long-bone x-rays; and other tests as clinically indicated (ophthalmologic evaluation, chest x-rays, neuroimaging, and auditory brain stem response).

Syphilis can cause many different abnormalities on long-bone x-rays, including

• Periosteal reactions

• Diffuse or localized osteitis

• Metaphysitis

The osteitis is sometimes described as "diffuse moth-eaten changes of the shaft." Metaphysitis commonly appears as lucent or dense bands that can alternate to give a sandwich or celery stalk appearance. The Wimberger sign is symmetric erosions of the upper tibia, but there can also be erosions in the metaphysis of other long bones. Excessive callus formation at the ends of long bones has been described. Many affected infants have more than one of these findings.

Diagnosis is confirmed by microscopic visualization of spirochetes in samples from the neonate or the placenta. Diagnosis based on neonatal serologic testing is complicated by the transplacental transfer of maternal IgG antibodies, which can cause a positive test in the absence of infection. However, a neonatal nontreponemal antibody titer > 4 times the maternal titer would not generally result from passive transfer, and diagnosis is considered confirmed or highly probable. Maternal disease acquired late in pregnancy may be transmitted before development of antibodies. Thus, in neonates with lower titers but typical clinical manifestations, syphilis is also considered highly probable. In neonates with no signs of illness and low or negative serologic titers, syphilis is considered possible; subsequent approach depends on various maternal and neonatal factors (see Follow up Follow up Congenital syphilis is a multisystem infection caused by Treponema pallidum and transmitted to the fetus via the placenta. Early signs are characteristic skin lesions, lymphadenopathy... read more

The utility of fluorescent assays for antitreponemal IgM, which is not transferred across the placenta, is controversial, but such assays have been used to detect neonatal infection. Any positive nontreponemal test should be confirmed with a specific treponemal test to exclude false-positive results, but confirmative testing should not delay treatment in a symptomatic infant or an infant at high risk of infection.

All seropositive infants and those whose mothers were seropositive should have VDRL or RPR titers every 2 to 3 months until the test is nonreactive or the titer has decreased 4-fold. In uninfected and successfully treated infants, nontreponemal antibody titers are usually nonreactive by 6 months. Passively acquired treponemal antibodies may be present for longer, perhaps 15 months. It is important to remember to use the same specific nontreponemal test to monitor titers in mothers, neonates, infants, and young children over time.

If VDRL or RPR remain reactive past 6 to 12 months of age or titers increase, the infant should be reevaluated (including lumbar puncture for CSF analysis, and complete blood count with platelet count, long-bone x-rays, and other tests as clinically indicated).

After adequate treatment, RPR and VDRL test results decrease 4-fold by 6 to 12 months in most patients and revert to negative by 2 years in nearly all patients. Erythromycin therapy is inadequate for both the mother and fetus and is not recommended. Tetracycline is contraindicated.

In confirmed or highly probable cases, the 2021 Centers for Disease Control and Prevention (CDC) STI treatment guidelines recommend aqueous crystalline penicillin G 50,000 units/kg IV every 12 hours for 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 IM once/day for 10 days ( see Table: Recommended Dosages of Selected Parenteral Antibiotics for Neonates Recommended Dosages of Selected Parenteral Antibiotics for Neonates

• Untreated

• Treatment status unknown

• Treated ≤ 4 weeks before delivery

• Inadequately treated (a nonpenicillin regimen)

• Maternal evidence of relapse or reinfection (≥ 4-fold increase in maternal titer)

In infants with possible syphilis whose mothers were not adequately treated but who are clinically well and have a completely negative full evaluation, a single dose of benzathine penicillin 50,000 units/kg IM is an alternative treatment choice in selected circumstances but only if follow-up is ensured.

Infants with possible syphilis whose mothers were adequately treated and who are clinically well also can be given a single dose of benzathine penicillin 50,000 units/kg IM. Alternatively, if close follow-up is ensured, some clinicians defer penicillin and do nontreponemal serologic testing monthly for 3 months and then at 6 months; antibiotics are given if titers rise or are positive at 6 months.

CSF should be examined before treatment starts. The CDC recommends that any child with late congenital syphilis be treated with aqueous crystalline penicillin G 50,000 units/kg IV every 4 to 6 hours for 10 days. A single dose of benzathine penicillin G 50,000 units/kg IM may also be given at the completion of the IV therapy. Alternatively, if a full evaluation is completely negative and the child is asymptomatic, benzathine penicillin G 50,000 units/kg IM once a week for 3 doses may be used.

Many patients do not revert to seronegativity but do have a 4-fold decrease in titer of reagin (eg, VDRL) antibody. Patients should be reevaluated at regular intervals to ensure the appropriate serologic response to therapy has occurred and that there is no indication of relapse.

Interstitial keratitis is usually treated with corticosteroid and atropine drops in consultation with an ophthalmologist. Patients with sensorineural hearing loss may benefit from penicillin plus a corticosteroid such as prednisone 0.5 mg/kg orally once/day for 1 week, followed by 0.3 mg/kg once/day for 4 weeks, after which the dose is gradually reduced over 2 to 3 months. Corticosteroids have not been critically evaluated in these conditions.