Syphilis is treated with antibiotics, and penicillin remains the gold standard after more than 75 years. A single injection can cure early-stage syphilis, while later stages require longer treatment. The specific approach depends on how far the infection has progressed, so the stage at diagnosis shapes everything about your treatment plan.
Treatment for Early-Stage Syphilis
Primary syphilis (the painless sore stage), secondary syphilis (the rash and flu-like symptom stage), and early latent syphilis (infected within the past year but no symptoms) are all treated the same way: a single intramuscular injection of long-acting penicillin G, delivering 2.4 million units in one visit. That’s it. One shot, and the bacteria are eliminated in the vast majority of cases.
The injection goes into a large muscle, typically the buttock. It can sting, and the site may be sore for a day or two. But the convenience of a one-dose cure is a major advantage, since it removes the risk of forgetting pills or stopping treatment early.
Treatment for Late Latent Syphilis
If you’ve had syphilis for more than a year, or if it’s unclear how long you’ve been infected, treatment takes longer. The total dose is 7.2 million units of penicillin G, split into three injections of 2.4 million units each, given one week apart. That means three clinic visits over three weeks.
Missing a dose in this series is a real concern. If too much time passes between injections, your provider may need to restart the sequence. Keeping those weekly appointments matters for a complete cure.
Neurosyphilis, Eye, and Ear Involvement
When syphilis reaches the brain, eyes, or inner ears, the stakes are higher and treatment is more intensive. These cases require intravenous penicillin delivered in a hospital or infusion center: 18 to 24 million units per day, given every four hours around the clock, for 10 to 14 days. This aggressive approach ensures the antibiotic reaches adequate levels in the spinal fluid, where the bacteria are harder to eliminate.
Neurosyphilis can occur at any stage of infection, not just late syphilis. Symptoms like vision changes, hearing loss, headaches, or difficulty with coordination should prompt immediate evaluation, because untreated neurosyphilis can cause permanent damage.
Options if You’re Allergic to Penicillin
For non-pregnant patients with a penicillin allergy, the main alternative is doxycycline: 100 mg taken by mouth twice daily for 14 days. Tetracycline (four times daily for 14 days) also works but is harder to stick with because of the dosing frequency. A third option, ceftriaxone given daily by injection or IV for 10 days, shows effectiveness in limited studies, though the ideal dose and duration aren’t fully established.
One antibiotic to be aware of: azithromycin. While a single large oral dose once showed promise, the syphilis-causing bacterium has developed resistance to it in multiple parts of the United States. It is no longer recommended.
If you have a penicillin allergy but there’s any concern you might not complete a full course of oral antibiotics, the preferred path is penicillin desensitization. This is a supervised process, done in a medical setting, where you receive gradually increasing doses of penicillin until your body tolerates it. After desensitization, you get the standard penicillin injection.
Treatment During Pregnancy
Pregnancy narrows the options considerably. Penicillin G is the only antibiotic proven to treat the fetus and prevent congenital syphilis. No alternative exists. Pregnant patients with a penicillin allergy must undergo desensitization and then receive penicillin, because the consequences of untreated syphilis in pregnancy (stillbirth, severe birth defects, neonatal death) are too serious to risk with a less proven drug.
The Jarisch-Herxheimer Reaction
Within the first 24 hours after your injection, you may experience what feels like a sudden flu: fever, chills, headache, muscle aches, nausea, and flushing. This is called the Jarisch-Herxheimer reaction, and it happens because dying bacteria release substances that trigger a burst of inflammation. It typically starts within two hours of treatment and resolves within 24 hours.
This reaction is not an allergic response to penicillin, and it does not mean the treatment is failing. If anything, it confirms the antibiotic is working. For most people, over-the-counter fever reducers like acetaminophen or aspirin are enough to manage the discomfort. Severe reactions, including significant drops in blood pressure, are rare and more likely in people with advanced disease. If you have existing skin lesions from syphilis, they may temporarily look worse before they heal.
Follow-Up Testing After Treatment
A single injection cures syphilis, but proving it’s cured requires follow-up blood tests. Your provider will track your nontreponemal antibody levels (the same type of blood test often used to diagnose syphilis) over time. The goal is a fourfold drop in those levels, which signals successful treatment. For example, a titer of 1:32 should fall to 1:8 or lower.
Follow-up testing typically happens at 6 and 12 months after treatment for early syphilis, and may extend to 24 months for late latent syphilis. If your levels don’t drop as expected, it could mean the treatment didn’t fully work or that you were reinfected, and additional evaluation or retreatment may be needed.
Notifying Sexual Partners
Treatment doesn’t end with your own injection. Sexual partners need to be evaluated and potentially treated to break the chain of transmission and protect you from reinfection. The look-back window depends on your stage at diagnosis:
- Primary syphilis: partners from the past 3 months, plus however long you had symptoms
- Secondary syphilis: partners from the past 6 months, plus symptom duration
- Early latent syphilis: partners from the past year
Many health departments offer confidential partner notification services, meaning a public health worker contacts your partners without revealing your identity. This can make an uncomfortable conversation easier while ensuring the people who need testing actually get it. Syphilis reinfection is common, and having a treated partner who then reinfects you puts you back at square one.
Why Penicillin Still Works
Unlike many other bacteria, the organism that causes syphilis has never developed resistance to penicillin. This is remarkable given that penicillin has been the primary treatment since the 1940s. The bacterium reproduces slowly and doesn’t easily acquire resistance genes, which is why a single dose of a long-acting formulation can wipe out an early infection. This also means that if you have access to treatment, syphilis is one of the most reliably curable sexually transmitted infections. The challenge has never been the treatment itself but rather getting people diagnosed and treated before the infection progresses.