Treatment of late latent syphilis or syphilis of unknown duration
Repeat serology on the day of treatment so that an accurate peak rapid plasma reagin [RPR] test titre is recorded to enable monitoring of the treatment responseOng, 2023.
Patients with central nervous system, eye or ear involvement require treatment with intravenous benzylpenicillin; see Treatment of neurosyphilis, ocular syphilis and otosyphilis.
Benzathine benzylpenicillin is long acting and the drug of choice for late latent syphilis or syphilis of unknown duration without central nervous system, eye or ear involvement. UseOng, 2023:
benzathine benzylpenicillin 2.4 million units intramuscularly1, every 7 days for 3 weeks. benzathine benzylpenicillin benzathine benzylpenicillin benzathine benzylpenicillin
Do not confuse benzathine benzylpenicillin with benzylpenicillin, which is short acting.
If a dose of benzathine benzylpenicillin is delayed, the 3-week course may need to be restarted; it is particularly important to avoid delaying doses during pregnancyWorkowski, 2021.
- For pregnant patients, the interval between doses of benzathine benzylpenicillin must not exceed 9 days; if this occurs, restart the course of therapy.
- For nonpregnant patients, if the interval between doses exceeds 14 days, restart the course of therapy.
Warn patients that they may experience a Jarisch–Herxheimer reaction – see Approach to managing syphilis for more information.
There are limited data supporting the use of nonpenicillin regimens for the treatment of syphilisOng, 2023. For patients who report penicillin hypersensitivity, verify their allergy. In some patients it may be appropriate to directly delabel their allergy by taking an extensive allergy history (see Clinical history for initial assessment of patients reporting penicillin hypersensitivity); in these patients benzathine benzylpenicillin should be used.
Seek expert advice for patients with a verified allergy. For patients who have had a nonsevere (immediate or delayed) or a severe (immediate)2 hypersensitivity reaction to a penicillin, options that an infectious diseases physician or clinical microbiologist may use include:
- performing desensitisation
- using a non–beta-lactam antibiotic.
For patients who have had a severe (delayed)3 hypersensitivity reaction to a penicillin, desensitisation should not be performed. A suitable option for nonpregnant patients, under expert guidance, isOng, 2023:
doxycycline 100 mg orally, 12-hourly for 28 days. doxycycline doxycycline doxycycline
For pregnant patients with penicillin hypersensitivity, seek expert advice – see also Syphilis in pregnancy and congenital syphilis.
For follow-up investigations to check treatment response, see Follow-up investigations for syphilis.
If there is a possibility that the patient has early syphilis, perform contact tracing as for early latent syphilis; see Management of sexual contacts of patients with early syphilis. For patients with late latent syphilis, perform serological testing for current sexual partners and treat according to the results. Late latent syphilis may have been acquired many years ago, so use the sexual history to determine if further contact tracing is required. See also STI contact tracing.