Syphilis Treatment: Penicillin Shots & Cure

Syphilis is cured with penicillin. For primary, secondary, or early latent disease, that means a single injection of benzathine penicillin G into the muscle; late or unknown-duration syphilis needs three weekly injections. There's no oral pill that reliably replaces it. A short flu-like reaction in the first day after the shot is expected and is not an allergy.

How syphilis is treated: the regimen and exact doses

Syphilis is caused by the bacterium Treponema pallidum, and it's curable with the right antibiotic given the right way CDC. Penicillin G, given by injection, is the preferred drug for every stage of the disease CDC STI Tx Guidelines. The dose changes not because the drug is stronger at later stages but because the bacteria divide slowly, so a longer schedule keeps penicillin in the body long enough to clear infection that's had more time to settle in.

The schedule follows the stage:

• Primary, secondary, and early latent syphilis: benzathine penicillin G 2.4 million units intramuscularly in a single dose CDC P&S Syphilis. The correct product is benzathine penicillin G (Bicillin L-A). The combination product Bicillin C-R is not an acceptable substitute — using it has caused treatment failures, so confirm the label.
• Late latent, unknown duration, and tertiary syphilis: benzathine penicillin G 7.2 million units total, given as three doses of 2.4 million units each at one-week intervals CDC Latent Syphilis.
• Neurosyphilis, ocular, or otosyphilis: aqueous crystalline penicillin G 18–24 million units per day, given as 3–4 million units IV every four hours (or by continuous infusion) for 10–14 days CDC Neurosyphilis. An alternative is procaine penicillin G 2.4 million units IM daily plus probenecid 500 mg orally four times daily, both for 10–14 days. These regimens usually require hospital or infusion-clinic care rather than a single office visit.

Early latent means infection acquired within the preceding year — documented by seroconversion, a fourfold or greater titer rise, or recent primary/secondary signs or a known exposure. Anything that can't be pinned to the last twelve months is treated as late latent or unknown duration. Your exposure history sets whether you get one shot or three.

If you're allergic to penicillin

For non-pregnant adults with a true penicillin allergy, primary, secondary, and early latent syphilis can be treated with doxycycline 100 mg orally twice daily for 14 days (or tetracycline 500 mg orally four times daily for the same period). Late latent or unknown-duration disease needs doxycycline 100 mg twice daily for 28 days; the 14-day course is not enough. Azithromycin is not recommended because of documented resistance. Most penicillin allergy is mislabeled — over 90% of people who believe they're allergic aren't when tested — so it's often worth confirming with your clinician before settling for a second-line drug.

Pregnancy

Penicillin is the only treatment that protects the baby. A pregnant person with syphilis at any stage who reports a penicillin allergy should be desensitized and treated with penicillin anyway; there's no safe alternative in pregnancy, and doxycycline isn't an option here. Because true allergy is far rarer than reported, desensitization is usually straightforward. Screening and prompt treatment matter for the baby's sake; see our guide to syphilis in pregnancy for the full prenatal picture.

What treatment is actually like

For early syphilis, treatment is one intramuscular injection — typically in the buttock or thigh, and it stings because the formulation is thick. Late or unknown-duration disease means returning weekly for three shots total. For most people the needle isn't the hard part. What can happen in the hours afterward is.

Within the first 24 hours — sometimes within a couple of hours — some people develop fever, chills, headache, and muscle aches. This is the Jarisch-Herxheimer reaction: dying bacteria release inflammatory signals all at once, and the body reacts StatPearls. It's most common when treating early syphilis, affecting roughly 95% of people treated for secondary disease, and it usually settles within about a day. This is not a penicillin allergy, and mistaking it for one can derail correct treatment. Treat the symptoms with rest and fever reducers, and don't abandon the regimen unless you have true allergy signs like hives or trouble breathing.

Do partners need treatment too?

Yes. Sexual partners exposed to someone with infectious syphilis should be evaluated and treated, because a partner can be infected before their own blood test turns positive. Treating only one person in a couple lets syphilis bounce straight back. If a recent partner tests negative, timing matters — a test taken too soon after exposure can miss the infection, so review when to test after exposure before assuming someone is in the clear. Partners who want to start can get tested and compare testing providers to find an option that fits.

Follow-up: how cure is confirmed

Feeling better doesn't prove you're cured; blood titers do. Cure is confirmed with repeat quantitative nontreponemal tests (RPR or VDRL), and the marker of success is a fourfold or greater decline in the titer, for example from 1:32 down to 1:8.

The follow-up schedule depends on stage:

• Primary and secondary syphilis: repeat titers at 6 and 12 months.
• Latent syphilis: repeat titers at 6, 12, and 24 months.

A fourfold rise in titer after treatment points to reinfection or treatment failure and means re-evaluation — which raises a question many people ask, answered in can you get syphilis again after treatment? The titer is your proof of cure, so skipping the follow-up blood draws is a mistake even when you feel completely well.

What happens if syphilis goes untreated

Syphilis is so often caught late because it feels like it's healing on its own. The first sore (the chancre) is usually painless and frequently hidden — inside the vagina, rectum, or mouth — and it heals without treatment. The sore disappears while the bacteria move inward. (If you're trying to tell a sore apart, see syphilis vs herpes — herpes sores typically hurt.)

Left untreated, the infection can progress to tertiary syphilis, which can damage the cardiovascular system, form destructive soft growths called gummas in skin, bone, or organs, and injure multiple organ systems years later. Two complications can appear at any stage, not just late: neurosyphilis (infection of the brain and spinal cord, which can cause stroke, confusion, or paralysis) and ocular syphilis (infection of the eye that can threaten vision) StatPearls. New vision changes or neurological symptoms in someone with syphilis are a medical emergency. Untreated syphilis also roughly doubles the risk of acquiring HIV, and in pregnancy it harms the baby in 50 to 80% of cases — stillbirth, prematurity, newborn death, or congenital infection WHO.

Preventing syphilis going forward

Treatment clears the current infection but doesn't make you immune; you can catch syphilis again. The core protections are correct and consistent condom use, mutual monogamy with a partner who has tested negative, and routine screening for anyone at ongoing risk. Diagnosis needs two tests — a screening test plus a confirmatory one — and early after exposure a test can read negative, so a recent risk calls for a repeat draw CDC Lab Recommendations, 2024.

For some people there's now a prophylactic option. DoxyPEP — 200 mg of doxycycline taken within 72 hours after sex — reduced syphilis acquisition by about 73% in trials and is recommended through shared decision-making for gay and bisexual men and transgender women who've had a bacterial STI in the past year CDC DoxyPEP, 2024. Discuss it with a clinician; it doesn't replace treatment or screening.

Syphilis is climbing. There were about 53,000 primary-and-secondary cases reported in 2023, and congenital syphilis — passed from parent to baby — nearly doubled in four years, reaching its highest level in decades CDC AtlasPlus, 2023. Rates also vary sharply by place, running several times the national average in states like South Dakota, New Mexico, and Mississippi and in Washington, DC.

How the stages compare at a glance

When to see a clinician

See a clinician promptly if you notice a painless sore, an unexplained rash (often on the palms and soles), or if a partner tells you they've tested positive. Seek urgent care for new vision changes, severe headache, confusion, or weakness, which can signal eye or nervous-system involvement at any stage. If you're pregnant, get screened early — congenital syphilis is preventable with prenatal screening plus penicillin, but only if it's caught.