Penicillin Treatment Regimens for Syphilis

For primary and secondary syphilis, the recommended treatment is a single dose of Benzathine penicillin G, 2.4 million units IM. 1

Treatment Regimens by Stage of Syphilis

Benzathine penicillin G, 2.4 million units IM in a single dose is the recommended regimen for adults with primary or secondary syphilis 2, 1
For children with acquired primary or secondary syphilis, the recommended dose is Benzathine penicillin G, 50,000 units/kg IM, up to the adult dose of 2.4 million units in a single dose 1

The recommended regimen is the same as for primary and secondary syphilis - Benzathine penicillin G, 2.4 million units IM in a single dose 1

Benzathine penicillin G, 7.2 million units total, administered as 3 doses of 2.4 million units IM each at 1-week intervals 1

Benzathine penicillin G, 7.2 million units total, administered as 3 doses of 2.4 million units IM each at 1-week intervals 1

Aqueous crystalline penicillin G, 12 to 24 million units per day, administered as 2-4 million units IV every 4 hours for 10-14 days 3
Many experts recommend additional therapy with Benzathine penicillin G 2.4 million units IM weekly for 3 doses after completion of IV therapy 3

For non-pregnant individuals allergic to penicillin with primary or secondary syphilis, doxycycline 100 mg orally twice daily for 14 days is the recommended alternative 4
For late latent syphilis or syphilis of unknown duration in penicillin-allergic patients, doxycycline 100 mg orally twice daily for 28 days is recommended 4
Doxycycline is preferred over tetracycline due to better compliance with twice-daily dosing versus four-times-daily dosing 4

The treatment regimens for HIV-infected patients are the same as for non-HIV-infected patients 1
However, closer monitoring at 3-month intervals instead of 6-month intervals is recommended for HIV-infected patients 4
A randomized clinical trial comparing single-dose versus 3-dose regimens of benzathine penicillin G for early syphilis in HIV-infected individuals found no significant difference in treatment success rates (93% vs 100% in per-protocol analysis) 5

Only penicillin G is proven effective for preventing maternal transmission of syphilis 1
Pregnant women with penicillin allergy should undergo desensitization and be treated with penicillin 1

Quantitative nontreponemal serologic tests should be repeated at 6,12, and 24 months after treatment 1
A 4-fold decline in titer is expected within 6 months for primary/secondary syphilis and within 12-24 months for late syphilis 1
Treatment failure is defined as failure of nontreponemal test titers to decline 4-fold within 6 months after therapy for primary or secondary syphilis 1
Re-treatment should be considered if titers increase 4-fold, an initially high titer fails to decline at least 4-fold within 12-24 months, or signs or symptoms attributable to syphilis develop 4

Persons exposed to a patient with primary, secondary, or early latent syphilis within the preceding 90 days should be treated presumptively, even if seronegative 2
Persons exposed more than 90 days before the diagnosis should be treated presumptively if serologic test results are not immediately available and follow-up is uncertain 2
Long-term sex partners of patients with late syphilis should be evaluated clinically and serologically 2

Despite decades of clinical experience with penicillin for syphilis treatment, there have been few adequately conducted comparative trials to guide the selection of optimal penicillin regimens 2
The "serofast state" (persistent positive nontreponemal tests despite adequate treatment) can occur and does not necessarily indicate treatment failure 6
CSF examination is not recommended for routine evaluation of patients with primary or secondary syphilis unless clinical signs or symptoms of neurologic involvement are present 2
Treatment failures can occur with any regimen, necessitating careful follow-up 2