Syphilis management for primary and secondary stages


 * Parenteral penicillin G has been used effectively for more than 50 years to achieve clinical resolution (i.e., the healing of lesions and prevention of sexual transmission) and to prevent late sequelae. However, no comparative trials have been adequately conducted to guide the selection of an optimal penicillin regimen (i.e., the dose, duration, and preparation). Substantially fewer data are available for non-penicillin regimens.


 * Available data demonstrate that additional doses of benzathine penicillin G, amoxicillin, or other antibiotics in (primary, secondary, and early latent syphilis do not enhance efficacy, regardless of HIV status.


 * Infants and children aged more than 1 month diagnosed with syphilis should have a CSF examination to detect asymptomatic neurosyphilis, and birth & maternal medical records should be reviewed to assess whether such children have congenital or acquired syphilis. Children with acquired primary or secondary syphilis should be evaluated (e.g., through consultation with child-protection services) and treated by using the following pediatric regimen.

CDC Recommendations: Pharmacotherapy
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Recommended Regimen for Adults
1. Benzathine penicillin G 2.4 million units IM in a single dose.

Recommended Regimen for Infants and Children
1. Benzathine penicillin G 50,000 units/kg IM, up to the adult dose of 2.4 million units in a single dose.}}

HIV-infection

 * All persons who have syphilis should be tested for HIV infection.


 * In geographic areas in which the prevalence of HIV is high, persons who have primary syphilis should be retested for HIV after 3 months if the first HIV test result was negative.

Neurosyphilis

 * Patients who have syphilis and symptoms or signs suggesting neurologic disease (e.g., meningitis and hearing loss) or ophthalmic disease (e.g., uveitis, iritis, neuroretinitis, and optic neuritis) should have an evaluation that includes CSF analysis, ocular slit-lamp ophthalmologic examination, and otologic examination. Treatment should be guided by the results of this evaluation.


 * Invasion of CSF by T. pallidum accompanied by CSF laboratory abnormalities is common among adults who have primary or secondary syphilis. Therefore, in the absence of clinical neurologic findings, no evidence exists to support variation from the recommended treatment regimen for early syphilis.


 * Symptomatic neurosyphilis develops in only a limited number of persons after treatment with the penicillin regimens recommended for primary and secondary syphilis. Therefore, unless clinical signs or symptoms of neurologic or ophthalmic involvement are present or treatment failure is documented, routine CSF analysis is not recommended for persons who have primary or secondary.

Penicillin Allergy: Alternative regimen

 * Data to support the use of alternatives to penicillin in the treatment of early syphilis are limited. However, several therapies might be effective in non-pregnant, penicillin-allergic patients who have primary or secondary syphilis.


 * Doxycycline 100 mg orally twice daily for 14 days and tetracycline (500 mg four times daily for 14 days) are regimens that have been used for many years.


 * Compliance is likely to be better with doxycycline than tetracycline, because tetracycline can cause gastrointestinal side effects.


 * Although limited clinical studies, along with biologic and pharmacologic evidence, suggest that ceftriaxone (1 g daily either IM or IV for 10-14 days) is effective for treating early syphilis, the optimal dose and duration of ceftriaxone therapy have not been defined.


 * Azithromycin as a single 2-g oral dose is effective for treating early syphilis.  However, T. pallidum chromosomal mutations associated with azithromycin resistance and treatment failures have been documented in several geographical areas in the United States.  As such, the use of azithromycin should be used with caution only when treatment with penicillin or doxycycline is not feasible. Azithromycin should not be used in MSM or pregnant women.


 * Close follow-up of persons receiving any alternative therapies is essential.


 * Persons with a penicillin allergy whose compliance with therapy or follow-up cannot be ensured should be desensitized and treated with benzathine penicillin.


 * Skin testing for penicillin allergy might be useful in some circumstances in which the reagents and expertise are available to perform the test adequately.

Pregnancy
Pregnant patients who are allergic to penicillin should be desensitized and treated with penicillin.

Follow-Up

 * Treatment failure can occur with any regimen. However, assessing response to treatment frequently is difficult, and definitive criteria for cure or failure have not been established.
 * In addition, nontreponemal test titers might decline more slowly for persons who previously have had syphilis.


 * Clinical and serologic evaluation should be performed 6 months and 12 months after treatment; more frequent evaluation might be prudent if follow-up is uncertain.


 * Patients who have signs or symptoms that persist or recur or who have a sustained fourfold increase in nontreponemal test titer (i.e., compared with the maximum or baseline titer at the time of treatment) probably failed treatment or were reinfected. These patients should be retreated and reevaluated for HIV infection.


 * Because treatment failure usually cannot be reliably distinguished from reinfection with T. pallidum, a CSF analysis also should be performed.


 * Although failure of nontreponemal test titers to decline fourfold within 6-12 months after therapy for primary or secondary syphilis might be indicative of treatment failure.


 * Clinical trial data have demonstrated that greater than 15% of patients with early syphilis treated with the recommended therapy will not achieve the two dilution decline in nontreponemal titer used to define response at 1 year after treatment.


 * Persons whose titers do not decline should be reevaluated for HIV infection.


 * Optimal management of such patients is unclear.


 * At a minimum, these patients should receive additional clinical and serologic follow-up.


 * If additional follow-up cannot be ensured, retreatment is recommended.


 * Because treatment failure might be the result of unrecognized CNS infection, CSF examination can be considered in such situations.


 * For retreatment, weekly injections of benzathine penicillin G 2.4 million units IM for 3 weeks is recommended, unless CSF examination indicates that neurosyphilis is present.


 * In rare instances, serologic titers do not decline despite a negative CSF examination and a repeated course of therapy. In these circumstances, the need for additional therapy or repeated CSF examinations is unclear, but is not generally recommended.