P&S Syphilis - STI Treatment Guidelines (2023)


Parenteral penicillin G has been used effectively to achieve clinical resolution (ie, lesion healing and prevention of sexual transmission) and to prevent late complications. However, no comparative studies have been performed to guide the selection of an optimal penicillin regimen. There is significantly less data available for non-penicillin therapies.

Recommended regimen for primary and secondary syphilis* in adults

Benzathine-Penicilin G2.4 million units IM in a single dose

* Recommendations for the treatment of syphilis in people living with HIV infection and in pregnant women are discussed elsewhere in this report (see Syphilis in People Living With HIV Infection; Syphilis During Pregnancy) .

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Available data indicate that the use of additional doses of benzathine penicillin G, amoxicillin, or other antibiotics does not improve the efficacy of this recommended regimen when used to treat primary and secondary syphilis, regardless of HIV status (591593).

Recommended regimen for syphilis in infants and children

Benzathine-Penicilin G50,000 units/kg body weight IM, up to the adult dose of 2.4 million units in a single dose

For infants and children ≥ 1 month of age who are diagnosed with syphilis, the mother's birth records and medical records should be reviewed to determine if they have congenital or acquired syphilis (see Congenital Syphilis). Infants and children ≥1 month with primary and secondary syphilis should be treated by a pediatric infectious disease specialist and evaluated for sexual abuse (eg, by consulting child protective services) (see Sexual Abuse or Child Abuse) .

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Other management considerations

All people with primary and secondary syphilis should be tested for HIV at the time of diagnosis and treatment. People who test negative for HIV should be offered HIV PrEP. In geographic areas with high HIV prevalence, people with primary or secondary syphilis should be offered PrEP and retested for HIV within 3 months if the initial HIV test result is negative.

Individuals with syphilis and symptoms or signs suggestive of a neurologic disorder (eg, cranial nerve dysfunction, meningitis, stroke, or altered mental status) should have an evaluation that includes CSF analysis. People with syphilis who have symptoms or signs of ocular syphilis (eg, uveitis, iritis, neuroretinitis, or optic neuritis) should have a complete cranial nerve exam, ocular slit lamp, and ophthalmologic examination. CSF tests are not always necessary in people with ocular syphilis if there are no signs of dysfunction of cranial nerves 2, 3, 4, 5, and 6 or other signs of neurologic disease. If there are symptoms and signs of otic syphilis, an otologic examination is required; CSF testing in persons with otic syphilis does not support clinical management and is therefore not recommended (see Cerebrospinal Fluid Evaluation). Treatment should be guided by the results of these evaluations. invaded by CSFt blassaccompanied by CSF laboratory abnormalities is common in adults with primary or secondary syphilis but is of unknown medical significance.585). In the absence of clinical-neurological findings, there is no evidence of a deviation from the recommended treatment regimen for primary or secondary syphilis. Symptomatic neurosyphilis after treatment with the penicillin regimens recommended for primary and secondary syphilis is rare. Therefore, routine CSF analysis is not recommended for persons with primary or secondary syphilis unless there are clinical signs or symptoms of neurologic or ophthalmic involvement.

Follow up

Clinical and serological investigations should be performed at 6 and 12 months after treatment; More frequent testing may be useful when follow-up is uncertain or when reinfection is a clinical problem. The serologic response (ie, titer) should be compared to the titer at the time of treatment. However, assessing serologic response to treatment can be difficult, and definitive criteria for cure or failure based on serologic criteria are not well established. In addition, nontreponemal test titers may decline more slowly in persons previously treated for syphilis (594,595).

People with persistent or recurrent signs or symptoms and people with at least a 4-fold increase in nontreponemal test titer that persists for more than 2 weeks are likely to have become reinfected or have failed treatment. CSF evaluation with CSF-guided management is recommended in individuals with neurologic findings or individuals without neurologic findings without reported sexual exposure in the past 3 to 6 months suggesting possible treatment failure. These people should also be retested for HIV infection.

In individuals with no neurological findings after a complete neurological examination and who are sexually active, reinfection is likely and repeat treatment for early syphilis is recommended. These people should also be retested for HIV infection.

Failure of nontreponemal test titers to decline fourfold within 12 months of treatment for primary or secondary syphilis (inadequate serologic response) could be indicative of treatment failure. However, data from clinical trials have shown that 10-20% of people with primary and secondary syphilis treated with recommended therapy fail to achieve a four-fold decrease in nontreponemal titer within 12 months. of treatment (591,596,597). Serologic response to treatment appears to be associated with several factors, including the stage of a person's syphilis (earlier stages are more likely to drop four-fold and become nonreactive), baseline nontreponemal antibody titers (titers <1 :8 less likely to drop four-fold than higher titers) and age (titers in older patients are less likely to drop four-fold than in younger patients) (596598). The optimal treatment of people who have an inadequate serologic response after treatment for syphilis is unclear. These individuals should receive additional neurologic evaluation, clinical and serologic follow-up, and reassessment for HIV infection at least annually. If neurological symptoms or signs are identified, CSF evaluation is recommended and the results guide management. If further follow-up care cannot be secured, repeat treatment is recommended. Because treatment failure may be the result of unrecognized CNS infection, CSF testing may be considered in situations where follow-up is uncertain.

For retreatment, weekly injections of 2.4 million units of benzathine penicillin G intramuscularly (IM) for 3 weeks are recommended unless CSF examination indicates the presence of neurosyphilis (see Neurosyphilis, Ocular Syphilis, and Otosyphilis). . Serologic titers may not decline despite a negative CSF test and 3-week repeat therapy (599). In these circumstances, the benefit of additional therapy or repeat CSF testing is unclear and is generally not recommended. Serological and clinical monitoring should be continued at least annually to control for sustained increases in nontreponemal titers.

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Management of sexual partners

See Syphilis, Dealing with Sexual Partners.

Special Considerations

penicillin allergy

Data supporting the use of alternatives to penicillin in the treatment of primary and secondary syphilis are limited. However, in nonpregnant people with penicillin allergy who have primary or secondary syphilis, multiple therapies may be effective. Doxycycline (100 mg orally 2 times a day for 14 days) (600,601) and tetracycline (500 mg po 4 times daily for 14 days) have been used for years and may be effective. Compliance is probably better with doxycycline than with tetracycline because tetracycline may cause more gastrointestinal side effects and require more frequent dosing. Limited clinical studies combined with biological and pharmacological evidence indicate that ceftriaxone (1 g daily either IM or IV for 10 days) is effective in the treatment of primary and secondary syphilis; however, the optimal dose and duration of therapy with ceftriaxone have not been defined (602,603). Azithromycin in a single oral dose of 2 g has been shown to be effective in certain populations for the treatment of primary and secondary syphilis.602,604,605). However due tot blassChromosomal mutations associated with resistance to azithromycin and other macrolides and documented treatment failure in various geographic areas of the US, azithromycin should not be used to treat syphilis.606608). Comprehensive clinical and serological follow-up of people receiving alternative therapy is essential.

Persons with penicillin allergy whose adherence to therapy or follow-up cannot be assured should be desensitized and treated with benzathine penicillin G. Skin testing for penicillin allergy may be helpful if the reagents and experience to perform the test appropriately are available (see Treatment of Persons With a History of Penicillin Allergy).

the pregnancy

Pregnant women with primary or secondary syphilis who are allergic to penicillin should be desensitized and treated with penicillin G. Skin tests or oral tests with graduated doses of penicillin may be helpful in identifying women at risk of acute allergic reactions (see Treatment of people with a history). penicillin allergy; syphilis during pregnancy).

HIV infection

HIV-infected people who have primary or secondary syphilis should receive treatment similar to HIV-negative people (see Syphilis in People with HIV infection).

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