Parenteral penicillin G is the standard therapy for syphilis. While this treatment has been used for over 50 years and its efficacy is well established, the recommendation is based on clinical studies and expert opinion rather than randomized clinical trials (16). It has been found that adequate treatment requires serum concentrations to be maintained above a threshold of 0.03 units/mL for 10 days (17). A single intramuscular dose of 2.4 million units of penicillin G will maintain a supratherapeutic level for two weeks. The CDC provides treatment recommendations based on the stage of disease, as well as associated comorbidities and other special circumstances (Table 1).

While a single dose of intramuscular penicillin G has been found to be highly effective in the early stages of syphilis, other situations may require more extensive treatment. Gummatous and cardiovascular tertiary syphilis should be treated with weekly doses of penicillin G given for three weeks. With one-third of latent syphilis cases advancing to the tertiary stage, those in the late or unknown stages of latency should also receive this regimen. Although not officially recommended by the CDC, many practitioners favor the extended three-week treatment for patients coinfected with HIV, even if only in the early stages of syphilis. All of these individuals should also undergo CSF examination prior to therapy to assess for possible CNS involvement. Neurosyphilis requires special care, as adequate bactericidal levels of antibiotic are not found in the CSF after a single dose of penicillin G (18). It is therefore recommended that neurosyphilis patients be treated with a 10- to-14-day course of intravenous penicillin and followed closely with serial testing of the CSF to ensure eradication. Pregnant women should receive treatment appropriate to the stage of their disease. As no other antibiotic has been shown to effectively treat the fetus, penicillin-allergic patients should undergo desensitization. If congenital infection does occur, the CDC recommends at least a 10-day course of intravenous aqueous penicillin G.

Data regarding the management of otosyphilis are lacking and there are no prospective clinical trials to support any given regimen. General consensus from a prior review of the literature suggests that an extended treatment with penicillin in combination with steroids is indicated (19). This literature review revealed practices ranging from weekly intramuscular injections to multiple intravenous infusions daily, with length of treatment anywhere from 15 days to 1 year. The CDC currently recommends that auditory syphilitic disease be treated the same as neurosyphilis: aqueous penicillin G given as three to four million units intravenously every four hours for 10 to 14 days. For those with questionable follow-up, an alternative is a one-time intramuscular dose of 2.4 million units of penicillin G followed by probenecid 500 mg orally, four times daily for 10 to 14 days. Data regarding corticosteroid usage are also lacking, and the above-referenced review by Darmstadt and Harris revealed a wide discrepancy in treatment regimens, but a tendency for better outcomes with combined antibiotic and steroid therapy. Their recommendation entails 40 to 60 mg of prednisone daily for a minimum of two weeks. If improvement occurs, the steroid can be slowly tapered until recurrence of symptoms. Long-term maintenance, if needed, should consist of alternate-day dosing.

Recommended follow-up is dependent on the stage at the time of treatment and should include serial serologic testing. Those with early syphilis should be assessed at 3, 6, and 12 months with expected seronegativity by one year. Patients with late latent or gummatous disease should have follow-up extended to two years to ensure seronegative

TABLE 1 CDC Recommended Syphilis Treatment Regimens

Stage/comorbidity Primary recommendation

Primary, secondary, or early latent disease in adults

Primary, secondary, or early latent disease in children Late latent syphilis or latent syphilis of unknown duration in adults Late latent syphilis or latent syphilis of unknown duration in children

Tertiary syphilis (gummatous or cardiovascular involvement; not neurosyphilis) Neurosyphilis (including otologic involvement)

Primary and secondary syphilis among HIV-infected persons Latent syphilis among

HIV-infected persons Syphilis during pregnancy

Congenital syphilis

Benzathine penicillin G 2.4 million units i.m. in a single dose

Benzathine penicillin G 50,000 units/kg i.m., up to the adult dose of 2.4 million units in a single dose Benzathine penicillin G 7.2 million units total, administered as 3 doses of 2.4 million units i.m. each at 1 wk intervals

Benzathine penicillin G 50,000 units/kg i.m., up to the adult dose of 2.4 million units, administered as 3 doses at 1 wk intervals (total 150,000 units/kg up to the adult total dose of 7.2 million units) Benzathine penicillin G 7.2 million units total, administered as 3 doses of 2.4 million units i.m. each at 1 wk intervals

Aqueous crystalline penicillin G 18-24 million units per day, administered as 3-4 million units i.v. every 4 hr or continuous infusion, for 10-14 days Benzathine penicillin G, 2.4 million units i.m. in a single dose

Benzathine penicillin G, at weekly doses of 2.4 million units for 3 wk Treatment during pregnancy should consist of the penicillin regimen appropriate for the stage of syphilis

Aqueous crystalline penicillin G, 100-150,000 units/kg i.v. daily in 2 or 3 divided doses for a minimum of 10 days or procaine penicillin G, 50,000 U/kg i.m. daily for a minimum of 10 days

Abbreviations-. CDC, Centers for Disease Control and Prevention; i.m., intramuscular; i.v., intravenous.

Alternative therapy

Data for alternative treatments are lacking. These regimens have been used in nonpregnant, penicillin-allergic patients: doxycycline (100 mg orally twice daily for 14 days) or tetracycline (500 mg 4 times daily for 14 days)

If compliance is questioned: Procaine penicillin 2.4 million units i.m. once daily plus Probenecid 500 mg orally 4 times a day, both for 10-14 days

No alternatives to penicillin have been proven effective for treatment of syphilis during pregnancy. Pregnant women who have a history of penicillin allergy should be desensitized and treated with penicillin results by the end of the second year. A fourfold increase in titers or lack of fourfold decrease in titers by 12 to 24 months suggests treatment failure (2). CSF examination and repeat treatment are then indicated. Cardiovascular involvement or neurosyphilis prompts the need for lifelong follow-up. Neurosyphilis should be followed with serologic and CSF examinations every three to six months until all antibody testing is negative.

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