New recommendations to deal with realities in the field

Long forgotten by the general public but well known to CEGIDD. Moreover, specialized consultations, syphilis remains largely underdiagnosed in the general population. Furthermore, The High Authority for Health (HAS) published in April 2025 a complete revision of its processing recommendations. Consequently, incorporating European data and updating therapeutic schemes in the face of realities on the ground. Therefore, Focus on new features.

Early syphilis: Penicillin Genzathine G (BPG) still in the lead. Moreover, doxycycline better framed – New recommendations deal realities field

For syphilis evolving for less than a year (primary, secondary, early latent), the Penicillin G Benzathine (2.4 Mui in intramuscular (IM) in one or two injections) remains the reference treatment.

In case of penicillin allergy. Consequently, impossibility of injection (coagulation disorders, anticoagulants), two alternatives are now clearly recommended:

• Doxycycline 200 mg/d for 14 days, in 1 to 2 catches,
• Ceftriaxone 1 g intravenous (IV) new recommendations deal realities field for 10 days in second intention.

Azithromycin is not recommended in the French context due to a high resistance rate (> 75 % of strains of Treponema pale).

The patient with syphilis must benefit from the appropriate advice on prevention of all IS Sexually transmitted infections. Therefore, sexual violence and pregnancy, and be offered, if necessary, an orientation facilitated towards devices such as the PrEP Pre-exhibition prophylaxis. Furthermore, PREP is a strategy that allows a seronegative person exposed to HIV to eliminate the risk of infection. Moreover, taking, continuously or “on demand”, anti-retroviral treatment based on Truvada®. HIV, post exposure treatments, or orthogeny centers. However, We will add, when it is suitable, a proposal for aid to notification to the partner.

Late syphilis: prolonged treatment. reinforced indications – New recommendations deal realities field

For latent syphilis over a year or unknown seniority, as well as new recommendations deal realities field for rare tertiary forms:

• Benzathine Pénicilline G (BPG) 2.4 Mui in Im × 3, on D1, J8, J15,
• In alternative, Doxycycline 200 mg/d for 28 days.

These forms, slower to evolve, require prolonged durations, whether for penicillin or oral alternatives.

Neurosyphilis. eye syphilis and otosyphilis: heavy infusions, limited alternatives – New recommendations deal realities field

The treatment is based on benzylpénicillin G (penicillin g) 20 MUI/J in IV for 10 to 14 days, in continuous or fractional infusion.

Ceftriaxone treatment can be envisaged as an alternative. or a relay to benzylpénicillin, in particular to simplify the methods of administration and promote return to home and the decrease in the length of hospitalization (grade C). Ceftriaxone should be administered in this IV indication to the dosage of 2 g per day for a total. duration of antibiotic therapy from 10 to 14 days.

In case of intolerance:

• Ceftriaxone 2 g/d new recommendations deal realities field IV × 10–14 days is an alternative.
• High dose doxycycline (200 mg × 2/d for 28 days) is cited as an option of last resort.

Any serious allergy must be the subject of an allergological opinion with possible induction of tolerance.

In the event of an ocular or hearing damage, an ophthalmological or ENT consultation in an emergency is compulsory.

Tertiary. cardiovascular syphilis: 3 penicillin injections or a month of doxycycline

The treatment of tertiary and cardiovascular syphilis remains classic: Benzathine Penicillin G (BPG) 2.4 Mui in IM, once a week for 3 weeks. In patients with sparrow prostheses, injection can be done in deltoids.

In case of unavailability of BPG. contraindication to injections (coagulation disorders, anticoagulants), an alternative is possible: Doxycycline 200 mg/d for 28 days, in 1 or 2 catches.

If the patient is allergic to penicillins, an allergological consultation is recommended. Without the possibility new recommendations deal realities field of desensitization, doxycycline remains the alternative of choice.

Note: Penicillin G procaine, used in other countries, is not available in France.

Syphilis. pregnancy: therapeutic emergency, limited alternatives

In pregnant women, treatment does not change: benzylpénicillin G according to the stage of the disease.

But in case of allergy. the HAS insists on the need:

• a rapid allergological consultation,
• of an induction of tolerance if the allergy is confirmed.

Doxycycline can be considered at 1^is quarter if the alternatives are impossible, but it does not prevent congenital syphilis. In this case, the newborn should be treated by BPG IV at birth.

Congenital syphilis: compulsory systemic treatment

Congenital. early or late syphilis must be treated by Benzylpénicillin G intravenous for 10 to 14 days, in a dose of 150,000 IU/kg/d, in continuous or discontinuous infusion.

An alternative by intramuscular route is only possible if the cerebrospinal fluid new recommendations deal realities field is normal. but it is more painful and little used.

Partner management: Clarification of deadlines. strategies

HAS recommends:

Two options according to the date of the report:

• <3 months: immediate preventive treatment or clinical and clinical serological monitoring (J0, S6, M3, M6),
• 3 months: serological surveillance alone.

Pregnant women exposed must always be treated, without waiting for serological confirmation.

Associated measures: Jarisch-Herxheimer’s reaction. pain, tolerance

• A feverish reaction is frequent in early syphilis (fever, aches, discomfort); It must be treated with paracetamol, and we can sometimes prevent it using corticosteroids.
• To prevent pain in injection, BPG can be diluted with lidocaine 1 % in order to reduce its intensity.
• HAS advises to monitor patients for 30 minutes after injection.

new recommendations deal realities field

Biological monitoring: TNT. reinfection

The HAS recommends carrying out a non -proneemic test (VDRL or RPR test) to M3, M6, M12. Not specific to the treponme but relatively sensitive. this serological test detects non -specific treponemal antibodies and makes it possible to assert the active nature of the disease.

• The objective is to divide the TNT by 4 at 6 and 12 months (eg VDRL of 32 → 8).
• If TNT remains ≥ 8, discuss a lumbar reprocessing or puncture.

A reinfection is defined by an increase in TNT of a factor ≥ 4.

To remember for practice

These 2025 recommendations reaffirm the primacy of penicillin in the treatment of syphilis, while integrating clear and graduated alternatives according to contraindications. They insist on therapeutic emergency in pregnant women. on vigilance with regard to neurological forms and on the importance of structured biological monitoring.
More broadly. they replace the management of syphilis in a global approach to sexual health: regular screening, support for notification, link with prevention devices such as PREP or IVG centers.