G is the preferred drug for treatment of all stages of syphilis. The efficacy of penicillin for the treatment of syphilis was well established through clinical experience before the value of randomized controlled clinical trials was recognized. Therefore, nearly all the recommendations for the treatment of syphilis are based on expert opinion reinforced by case series, open clinical trials, and 50 years of clinical experience.
G is the only therapy with documented efficacy for neurosyphilis or for syphilis during pregnancy.
Patients with neurosyphilis and pregnant women with syphilis in any stage who report penicillin allergy should almost always be treated with penicillin, after desensitization, if necessary. However, minor determinants needed for penicillin skin testing are not available commercially. The Jarisch-Herxheimer reaction is common among patients with early syphilis. Antipyretics may be recommended, but there are no proven methods for preventing this reaction. The Jarisch-Herxheimer reaction may induce early labor or cause fetal distress among pregnant women.