Syphilis treatment
This chapter will summarize various syphilis treatment options.
Treatment is needed to get rid of syphilis. Untreated syphilis can lead to serious health consequences: permanent damage to the brain, eyes, nerves, heart, joints, and other organs.
The treatment for syphilis (the choice of medication and, especially, the duration of treatment) depends on its stage: early or late. The earlier it is treated, the easier it is to treat and the better the outcome.
Since syphilis screening is dramatically improved these days, most syphilis is diagnosed in the early stage or late latent stage. The focus of this chapter will be on the most commonly treated syphilis cases.
Early syphilis treatment, with all its subcategories—primary, secondary and early latent—will be discussed here. Early syphilis means the patient has had syphilis for not more than one year.
Only one category of late syphilis—late latent syphilis—will be discussed here.
This chapter will present tables with concise information on these topics:
- Primary syphilis
- Secondary syphilis
- Early latent syphilis
- Late latent syphilis
The tables will be followed by frequently asked questions, where an expert doctor will answer real-life patient questions and, in the process, elaborate on some important syphilis treatment issues.
Let’s start.
Primary syphilis is the first stage of syphilis. It presents with a chancre (sore) at the entry site and localized lymph node enlargement.
| Ideal (preferred) treatment | Alternative treatment |
|---|
Benzathine penicillin G (BPG)
2.4 million units
Intramuscular injection
Single dose
| Doxycycline
100 mg
Oral tablets
Twice daily for 2 weeks
OR
Ceftriaxone
1–2 grams per day
IM or IV
For 10–14 days
OR
Tetracycline
100 mg
Oral tablets
4 times a day for 2 weeks
OR
Azithromycin
2 grams
Single dose
(only if other options are infeasible) |
Twenty-five percent of people will develop secondary syphilis: syphilis spreads from the primary site, causing rash, patchy hair loss, lymphadenopathy (enlarged lymph nodes), and other symptoms
| Ideal (preferred) treatment | Alternative treatment |
|---|
Benzathine penicillin G (BPG)
2.4 million units
Intramuscular injection
Single dose
| Doxycycline
100 mg
Oral tablets
Twice daily for 2 weeks
OR
Ceftriaxone
1–2 grams per day
IM or IV
For 10–14 days
OR
Tetracycline
100 mg
Oral tablets
4 times a day for 2 weeks
OR
Azithromycin
2 grams
Oral tablets
Single dose
(only when other options are infeasible) |
Treatment regimen for early latent syphilis
A patient has latent syphilis when they have a positive blood test but no signs or symptoms of the disease.
Early latent syphilis means the person has had syphilis for less than a year—within the last year, they’ve had a negative syphilis test. The patient is considered infectious at this stage.
| Ideal (preferred) treatment | Alternative treatment |
|---|
Benzathine penicillin G (BPG)
2.4 million units
Intramuscular injection
Single dose
| Doxycycline
100 mg
Oral tablets
Twice daily for 2 weeks
OR
Tetracycline
500 mg
Orally
4 times a day for 4 weeks
|
Treatment regimen for late latent syphilis
A patient has latent syphilis when they have a positive blood test but no signs or symptoms of the disease.
Late latent syphilis means the person has had syphilis longer than a year. This is based on the last negative syphilis test. If the timing of an infection is not known, late latent syphilis is presumed. Syphilis transmission is unlikely at this stage.
| Ideal (preferred) treatment | Alternative treatment |
|---|
Benzathine penicillin G (BPG)
2.4 million units
Intramuscular injection
Three doses total—one per week
| Doxycycline
100 mg
Oral tablets
Twice daily for 4 weeks
OR
Tetracycline
500 mg
Orally
4 times a day for 4 weeks
|
Treatment algorithm for syphilis-positive adults
Frequently Asked Questions
In this section, our expert doctor will talk about a few aspects of syphilis treatment in more depth. We have reviewed real-life patient questions and grouped them into topics so the doctor can answer them efficiently.
Dr. Fuzayloff has been a practicing physician at a busy STD center in Midtown Manhattan, NYC, for over two decades.
Does testing have to be done before I can get treatment for syphilis? 
If a person has signs and symptoms of syphilis, we treat syphilis empirically (based on assumptions) the same day.
Ideally, testing should be done to confirm the diagnosis before the treatment is administered to establish the pretreatment titer (RPR titer). This is necessary to evaluate the response to treatment—the RPR titer should decline after treatment.
What is the medication of choice?
Penicillin is the medication of choice for all stages of syphilis. A specific type of penicillin (penicillin G) is used. It should be administered via intramuscular injection. The dosage and the duration of treatment depend on the stage of the disease.
What can you tell me about the special type of penicillin that’s used to treatment syphilis?
Syphilis should be treated with long-acting penicillin (brand name: Bicillin). To kill the infection effectively, the penicillin level should be maintained at a certain level (>0.018 mcg/ml) without interruption for more than 24 hours for about 10 days.
There are two types of Bicillin, Bicillin L-A and Bicillin C-R. They have the same concentration of penicillin, but Bicillin L-A, unlike Bicillin C-R, can maintain a persistent penicillin level for more than four weeks (Bicillin C-R can do so only for seven days).
So, Bicillin L-A (2.4 million units) is the ideal treatment. The number of shots and the duration of treatment depend on staging.
Why is penicillin given as an injection of a muscle?
Giving penicillin via the muscular route can be pretty painful, but this is the simplest way to maintain a continuous level of penicillin in all tissues. It keeps the concentration of penicillin at the necessary level for up to 30 days.
Is antibiotic sensitivity tested before treatment?
The initial antibiotic treatment for syphilis is chosen based on the response of the most people (according to statistics). No major resistance to penicillin has been reported in many decades of use.
The cure rate is 90% to 100%.
Sensitivity testing is not performed because the infection that causes syphilis, Treponema pallidum, is not readily grown in the laboratory.
I’m allergic to penicillin. What are my options?
If you’re allergic to penicillin, one option is to get desensitized to penicillin. You will be tested to confirm your penicillin allergy at an allergist’s office and, if that test is positive, desensitized to penicillin if possible.
The other option is to get alternative treatment. If you have primary syphilis or early latent syphilis, alternative medication is offered and post-treatment testing is closely monitored. Alternative medications are from the tetracycline and cephalosporin families.
What are the alternative treatments for syphilis?
Alternative treatment is offered to people who are allergic to penicillin or when penicillin G is not available. The duration of treatment depends on staging.
Early syphilis (primary, secondary, early latent), or syphilis for less than 1 year
- Doxycycline is the medication of choice—100 mg twice a day for 14 days. The response rate is 83% to 100%.
- If penicillin G is not available and person is not allergic to penicillin amoxicillin (3 grams) plus probenecid (500 mg) twice a day for 14 days. The cure rate is over 95%.
Late syphilis
For late syphilis, it is ideal to not use alternative options; it’s better to be desensitized to penicillin. But if alternative medication is necessary, the choice would be doxycycline 100 mg twice a day for 28 days.
How is the response to syphilis treatment monitored?
Syphilis’s response to treatment is monitored via nontreponemal tests: RPR or VDRL. The initial titer should decline. If the initial test while establishing the diagnosis was RPR (or VDRL), the same test should be done in follow-up.
There are no specific criteria for successful syphilis treatment, but there is a common understanding in medicine that in patients with primary or secondary syphilis, an RPR or VDRL titer should decline fourfold within six months, and for latent syphilis the same fourfold drop is expected by one year.
When is syphilis treatment considered to have failed?
If the titer of nontreponemal tests (RPR or VDRL) does not decrease, and especially if it is increasing, the provided treatment is considered a failure.
The exception to this rule is that if the initial RPR (or VDRL) titer was low—less than 1:8 at the time of the diagnosis—the titer can stay the same and the patient person is not infectious and considered cured.
What about treatment for late syphilis?
A patient is considered to have late syphilis if their blood test is positive, they have no symptoms, and they’ve had syphilis for longer than a year or the duration of their syphilis is unknown.
The duration of a syphilis infection is considered unknown unless a negative test within a year is available.
Late syphilis requires a longer duration of treatment.
Preferred treatment
Late syphilis is ideally treated with penicillin G, not an alternative. (How to address an allergy to penicillin was explained earlier.) One shot of penicillin G, 2.4 million units, should be administered weekly for three weeks.
Patient adherence to getting their shots on time is very important. If the second or third shot was not obtained within two weeks after the last one, the treatment should be reinitiated.
Select other section
X
