Antibiotic therapy for early syphilis

For features of early syphilis, see Features of the clinical stages of syphilis.

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 early syphilis without central nervous system, eye or ear involvement. UseBritish Association for Sexual Health and HIV (BASHH), 2019Ong, 2023Workowski, 2021:

benzathine benzylpenicillin 2.4 million units intramuscularly1, as a single dose. benzathine benzylpenicillin benzathine benzylpenicillin benzathine benzylpenicillin

Do not confuse benzathine benzylpenicillin with benzylpenicillin, which is short acting.

Some experts recommend a second dose of intramuscular benzathine benzylpenicillin (1 week after the first dose) for pregnant patients diagnosed with early primary or secondary syphilis – seek expert advice to determine if this is requiredAustralian Society for Infectious Diseases (ASID), 2022Workowski, 2021.

Advise patients to abstain from sexual contact for 7 days after treatment starts, or until treatment is completed and symptoms have resolved, whichever occurs laterOng, 2023.

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:

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 14 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.

1 The ventrogluteal site is preferred for administration of intramuscular benzathine benzylpenicillin because of reduced pain and risk of nerve injury. For instructions on intramuscular injection at the ventrogluteal site, see Instructions for intramuscular injection at the ventrogluteal site.Return
2 Severe immediate hypersensitivity reactions include anaphylaxis, compromised airway, airway angioedema, hypotension and collapse.Return
3 Severe delayed hypersensitivity reactions include cutaneous adverse drug reactions (eg drug rash with eosinophilia and systemic symptoms [DRESS], Stevens–Johnson syndrome/toxic epidermal necrolysis [SJS/TEN], severe blistering or desquamative rash), and significant internal organ involvement (eg acute interstitial nephritis).Return