ADULT SYPHILIS STAGING, TREATMENT AND PARTNER MANAGEMENT

STAGE & PARTNER

DIAGNOSTIC CRITERIA TREATMENT
SYMPTOMS MANAGEMENT

PRIMARY Exam finding consistent with primary syphilis Benzathine penicillin G 2.4 • If exposed ≤ 90 days of
at the time of treatment. million units IM in a single dose diagnosed case, partner(s)
Chancre • Presence of one or more chancres (i.e., firm, round, should be tested AND
small, painless, rubbery or indurated anogenital ALTERNATIVE REGIMEN* treated.
HIGHLY or oral ulcer) appear at the site of infection
(for a nonpregnant patient with
INFECTIOUS a documented penicillin allergy) • If exposure ≥ 90 days
• Presence of multiple or atypical anogenital Doxycycline 100 mg orally testing is sufficient
primary lesions 2x/day for 14 days, (unless opportunity for follow-
• Lesion(s) can sometimes be confirmed with OR up is uncertain, then test and
dark field or T pallidum PCR testing treat).
Tetracycline 500mg orally
4x/day for 14 days
+/– Serologic evidence of infection (or reinfection):
Reactive syphilis serologic results support the
diagnosis but may be absent in early primary syphilis.

SECONDARY Laboratory evidence of syphilis infection Benzathine penicillin G 2.4 • If exposed ≤ 90 days of
(or reinfection) million units IM in a single dose diagnosed case, partner(s)
Rash or AND Exam findings consistent with secondary should be tested AND
mucocutaneous syphilis: ALTERNATIVE REGIMEN* treated.
lesion (for a nonpregnant patient with
• Mucocutaneous eruption (localized or generalized), a documented penicillin allergy) • If exposure ≥ 90 days
HIGHLY including palmar or plantar rashes Doxycycline 100 mg orally testing is sufficient
2x/day for 14 days, (unless opportunity for follow-
INFECTIOUS • Condyloma lata
OR up is uncertain, then test and
• Mucous Patches treat).
Tetracycline 500mg orally
• Generalized lymphadenopathy, malaise, fever, other 4x/day for 14 days
nonspecific constitutional symptoms
• Patchy alopecia
STAGE & PARTNER
DIAGNOSTIC CRITERIA TREATMENT
SYMPTOMS MANAGEMENT

EARLY Non- Serologic evidence of syphilis infection Benzathine penicillin G 2.4 • If exposed ≤ 90 days of
Primary, Non- (or reinfection) million units IM in a single dose diagnosed case, partner(s)
Secondary AND No exam findings of primary, secondary, should be tested AND
(Formerly Early or tertiary syphilis ALTERNATIVE REGIMEN* treated.
Latent) (for a nonpregnant patient with • If exposure ≥ 90 days
AND Any of the following: a documented penicillin allergy) testing is sufficient
• Documented seroconversion within the past 12 Doxycycline 100 mg orally 2x/
No symptoms (unless opportunity for follow-
months (i.e., currently reactive syphilis serology with day for 14 days, up is uncertain, then test and
nonreactive results document in the past 12 months) OR
INFECTIOUS treat).
• A sustained rise (> 2 weeks) in nontreponemal test Tetracycline 500mg orally 4x/
titer of 2 or more dilutions (i.e., ≥ 4-fold rise) within day for 14 days
the past 12 months
• Symptoms of primary or secondary syphilis with past
12 months
• Sexual or needle-sharing contact with a person
diagnosed with primary, secondary, or early latent
syphilis during the past 12 months.
• Only possible exposure was within the last 12
months (e.g., sexual debut)

LATE LATENT Serologic evidence of infection (or reinfection) Benzathine penicillin G 7.2 Long-term sex partners (>1
AND No exam finding of primary, secondary, or million units total, administered year) should be evaluated
No symptoms tertiary syphilis at the time of treatment as three doses of 2.4 million clinically and serologically
units IM each at 1-week for syphilis and treated on
AND Criteria is not met for early latent syphilis
NOT INFECTIOUS intervals the basis of the evaluation’s
AND Evidence suggests that the infection findings.
was acquired greater than 12 months prior to ALTERNATIVE REGIMEN*
diagnosis. (for a nonpregnant patient with
a documented penicillin allergy)
Doxycycline 100 mg orally 2x/
day for 28 days,
OR
Tetracycline 500mg orally 4x/
day for 28 days
STAGE & PARTNER
DIAGNOSTIC CRITERIA TREATMENT
SYMPTOMS MANAGEMENT

LATENT OF Serologic evidence of infection (or reinfection) Benzathine penicillin Evaluation and presumptive
UNKNOWN AND No exam finding of primary, secondary, or G 7.2 million units total, treatment of contacts
DURATION tertiary syphilis at the time of treatment administered as three doses exposed within 12 months
AND Criteria is not met for early latent syphilis of 2.4 million units IM each at of first serologic evidence of
No symptoms 1-week intervals infection, or re-infection in the
AND Available information is insufficient to case-patient.
determine the duration of infection. ALTERNATIVE REGIMEN*
NOT INFECTIOUS
(for a nonpregnant patient with a
documented penicillin allergy)
Doxycycline 100 mg orally 2x/
day for 28 days,
OR
Tetracycline 500mg orally 4x/
day for 28 days

TERTIARY Clinical manifestations of late syphilis including: Testing for HIV infection and Long-term sex partners (>1
• Cardiovascular disease CSF examination should be year) should be evaluated
Varied • Gummatous disease of the skin or other organs performed before therapy is clinically and serologically
• Late neurologic complications (e.g., tabes dorsalis initiated. for syphilis and treated on
NOT INFECTIOUS or general paresis) With normal CSF the basis of the evaluation’s
examination: Benzathine findings.
AND Laboratory evidence of infection by serologic,
CSF, or direct pathology testing penicillin G 7.2 million units
total, administered as three
doses of 2.4 million units IM
each at 1-week intervals
With CSF abnormalities:
Treat with neurosyphilis
regimen.
Note: Providers treating
patients with cardiovascular
syphilis with a neurosyphilis
regimen should be managed in
consultation with an infectious
disease specialist.
 STAGE & PARTNER
DIAGNOSTIC CRITERIA TREATMENT
SYMPTOMS MANAGEMENT

NEUROSYPHILIS Clinical manifestations including early syndromes Aqueous crystalline penicillin Ocular, otic, or neurosyphilis
/OCULAR/OTIC (e.g., syphilitic meningitis, meningovascular G 18–24 million units per day, can occur during any
syphilis) and late complications of untreated administered as 3–4 million stage. Follow applicable
Varied infection usually following a long latency period units IV every 4 hours, or by stage partner management
(e.g., general paresis and tabes dorsalis). continuous infusion, for 10–14 guidance.
Ocular and otologic involvement can occur at any days
stage of syphilis
ALTERNATIVE REGIMEN*
Procaine penicillin G 2.4 million
units IM once daily for 10–14
days
PLUS
Probenecid 500mg orally 4x/
day for 10–14 days

* Parenteral penicillin G is the only therapy with documented efficacy for syphilis during pregnancy. Pregnant women with
syphilis in any stage who report penicillin allergy should be desensitized and treated with penicillin G. See 2021 STD Treatment
Guidelines for Management of Persons Who Have a History of Penicillin Allergy: https://www.cdc.gov/std/treatment-guidelines/
STI-Guidelines-2021.pdf