Table 3

Mechanisms of antibiotic resistance and recommendations for treatment of T pallidum

Antimicrobial agent or classDescribed mechanisms of resistanceRecommendations for current use
PenicillinsNo penicillin resistance documented in T pallidum

  • Benzathine penicillin G is recommended for all stages of syphilis, except neurosyphilis

  • For symptomatic or asymptomatic neurosyphilis, aqueous crystalline penicillin G or aqueous procaine penicillin G + probenecid are recommended

  • When possible, penicillin desensitisation is the preferred option for treating penicillin allergic patients who are pregnant or have neurosyphilis

TetracyclinesNo tetracycline resistance documented in T pallidumDoxycycline and tetracycline are recommended for persons with penicillin allergy, except during pregnancy. Compliance may be problematical, and penicillin is preferred if possible
MacrolidesChromosomal point mutations in the 23sRNA genes (A2058G and A2059G)Macrolides, including azithromycin and erythromycin (which was formerly recommended as an alternative for penicillin allergic persons) should be used only when penicillin or tetracyclines cannot be used. Macrolides should be used with caution unless the prevalence of resistance in locally circulating strains of T pallidum is known to be very low. If macrolides are used, careful follow-up must be assured. Infected infants have been born to pregnant women treated with macrolides during pregnancy, due to poor penetration of this class of drugs to the fetus. With the increasing prevalence of macrolide-resistant strains of T pallidum, the risk of macrolide treatment failure is further heightened
CephalosporinsNo cephalosporin resistance documented in T pallidumLimited clinical experience and pharmacokinetics data suggest that ceftriaxone should be effective for all stages of syphilis, although optimal dose and duration have not been determined. Penicillin allergy may crossreact with ceftriaxone in some individuals