infectious diseases
Syphilis
Treatment of Syphilis
Benzathinepenicillin Gfor most infections Aqueous penicillin for ocular syphilis or neurosyphilis Treatment of sex partners Thetreatment of choice in all stagesof syphilis and during pregnancy is The sustained-release penicillin benzathine penicillin (Bicillin L-A) The combination of benzathine and procaine penicillin (Bicillin C-R) shouldnotbe used. All sex partners of a patient diagnosed with syphilis should be evaluated. Sex partners are treated in the following circumstances: People who had sexual contact with a patient within the 90 days before the patient was diagnosed with primary, secondary, or early latent syphilis should be treated presumptively for early syphilis, even if serologic test results are negative. People who had sexual contact with a patient > 90 days before the patient was diagnosed with primary, secondary, or early latent syphilis should be treated presumptively for early syphilis if serologic test results are not immediately available and the opportunity for follow-up is uncertain. If serologic tests are negative, no treatment is needed. If serologic tests are positive, treatment should be based on clinical and serologic evaluation and stage of syphilis. (See alsoCenters for Disease Control and Prevention: Sexually Transmitted Infections Treatment Guidelines, 2021: Syphilis.) Use only pure benzathine penicillin (Bicillin L-A) for syphilis; do not use the similarly named combination of benzathine and procaine penicillin (Bicillin C-R). Benzathinepenicillin G2.4 million units IM given once produces blood levels that are sufficiently high for 2 weeks to cure primary, secondary, and early (<1 year) latent syphilis. Doses of 1.2 million units are usually given in each buttock to reduce local reactions. Additional doses of 2.4 million units should be given 7 and 14 days after the first (total of 3 doses) for late (>1 year) latent syphilis or latent syphilis of unknown duration because treponemes occasionally persist in the CSF after single-dose regimens. Treatment is the same regardless of HIV status. For nonpregnant patients with a significant penicillin allergy (anaphylactic, bronchospastic, or urticarial), the first alternative isdoxycycline100 mg orally twice a day for 14 days (28 days for late latent syphilis or latent syphilis of unknown duration).Azithromycin2 g orally in a single dose is effective for primary, secondary, or early latent syphilis caused by susceptible strains. However, a single mutation that increases resistance is increasingly common in many parts of the world, including the US, and results in unacceptably high failure rates. Azithromycinshould not be used to treat pregnant women or late latent syphilis. Pregnant patients with a penicillin allergy should be hospitalized and desensitized to penicillin. Ceftriaxone1 g IM or IV once a day for 10 to 14 days has been effective in some patients with early syphilis and may be effective at later stages, but optimal dose and duration of therapy are unknown. Late latent syphiliscan be treated with benzathinepenicillin G7.2 million units total, administered as 3 doses of 2.4 million units IM each at 1-week intervals. Benign or cardiovascular tertiary syphiliscan be treated in the same way as late latent syphilis. Forocular syphilis, otic syphilis, or neurosyphilis,one of the following is recommended: Aqueous penicillin 3 to 4 million units IV every 4 hours (penetrates the central nervous system best but may be impractical) Procainepenicillin G2.4 million units IM once a day plus 500 mgprobenecidorally 4 times a day Both medications are given for 10 to 14 days, followed by benzathine penicillin 2.4 million units IM once a week for 1 to 3 weeks after completion of these neurosyphilis treatment regimens to provide a total duration of therapy comparable to that for late latent syphilis. For patients who have penicillin allergies,ceftriaxone2 g IM or IV once a day for 14 days can be effective, but cross-sensitivity with cephalosporins may be a concern. The alternative is penicillin desensitization becauseazithromycinanddoxycyclinehave not been adequately evaluated in patients with neurosyphilis. Patients withtabes dorsalisand lightning pains should be given analgesics as needed;carbamazepine200 mg orally 3 or 4 times a day sometimes helps. Most patients with primary or secondary syphilis, especially those with secondary syphilis, have a JHR within 6 to 12 hours of initial treatment. It typically manifests as malaise, fever, headache, sweating, rigors, anxiety, or a temporary exacerbation of the syphilitic lesions. The mechanism is not understood, and JHR may be misdiagnosed as an allergic reaction. JHR usually subsides within 24 hours and poses no danger. However, patients with general paresis or a high CSF cell count may have a more serious reaction, including seizures or strokes, and should be warned and observed accordingly. Unanticipated JHR may occur if patients with undiagnosed syphilis are given antitreponemal antibiotics for other infections. After treatment, patients should have Examinations and reaginic tests at 3, 6, and 12 months and annually thereafter until the test is nonreactive or until a durable 4-fold reduction in titer is achieved For neurosyphilis, CSF testing every 6 months until CSF cell count is normal The importance of repeated tests to confirm cure should be explained to patients before treatment. Examinations and reaginic tests should be done at 3, 6, and 12 months after treatment and annually thereafter until the test is nonreactive. Failure of titers to decline by 4-fold at 6 months suggests treatment failure. After successful treatment, primary lesions heal rapidly, and plasma reaginic titers fall and usually become qualitatively negative within 9 to 12 months. In about 15% of patients with primary or secondary syphilis treated as recommended, the reaginic titer does not decrease by 4-fold—the criterion used to define response at 1 year after treatment. These patients should be followed clinically and serologically; they should also be evaluated for HIV infection. If neurologic symptoms or signs are identified, a CSF evaluation is recommended, with findings guiding management. If follow-up cannot be ensured, CSF should be checked for neurosyphilis (because unrecognized neurosyphilis may be the cause of treatment failure), or patients should be retreated with benzathine penicillin 2.4 million units IM once a week for 3 weeks. Treponemal tests may remain positive for decades or permanently and should not be measured to monitor progress. Serologic or clinical relapse, usually affecting the nervous system, may occur after 6 to 9 months, but the cause may be reinfection rather than relapse. Patients with neurosyphilis without HIV infection or those with HIV infection who are on effective ART and who exhibit serologic (normalization of the serum RPR titer) and clinical responses after treatment do not need repeated CSF examinations. In HIV-infected patients, persisting CSF pleocytosis may represent effects of HIV rather than persisting neurosyphilis. Normal CSF cell count, negative CSF and serum reaginic test results, and negative neurologic examination findings for 2 years indicates probable cure. If any of the following is present, retreatment with a more intensive regimen of antibiotics is indicated: CSF cell count that remains abnormal for > 2 years A serum reaginic test that remains reactive for > 2 years An increasing serum reaginic test titer Clinical relapse 