Syphilis is an infection caused by the bacterium Treponema pallidum, a spiral-shaped organism. This highly contagious condition is primarily transmitted through sexual contact and progresses through various stages if left untreated. Syphilis is curable using antibiotics. Treatment success depends on selecting the correct antibiotic and adjusting the regimen based on the infection’s stage.
The Primary Antibiotic Treatment
The standard, first-line treatment for all stages of syphilis is Penicillin G. This medication is uniquely effective because Treponema pallidum has not developed resistance to it. Penicillin G works by interfering with the bacteria’s ability to build its cell wall, leading to the destruction of the spirochete.
The preferred preparation is Benzathine Penicillin G, administered as an intramuscular injection. This formulation releases the medication slowly, maintaining therapeutic levels in the bloodstream for up to four weeks. This sustained concentration is important because T. pallidum divides slowly, requiring prolonged antibiotic activity for complete eradication.
The long-acting nature of Benzathine Penicillin G means a single injection can often cure early stages of the disease. This intramuscular delivery is the most reliable treatment option, avoiding compliance issues associated with multi-day oral regimens. Other penicillin preparations are not recommended because they fail to provide the necessary sustained drug levels.
Adjusting Treatment Based on Disease Stage
The required antibiotic regimen changes significantly based on the infection stage, which reflects how long the bacteria have been present. Syphilis is categorized into early or late stages, and this distinction determines the dosage and frequency of Benzathine Penicillin G injections.
Early syphilis includes primary, secondary, and early latent infections lasting less than one year. The standard treatment is a single 2.4 million unit intramuscular dose of Benzathine Penicillin G. This single injection is sufficient because the bacterial load is lower and the spirochetes are actively dividing, making them highly susceptible.
Late latent syphilis (more than one year) or syphilis of unknown duration requires an extended treatment protocol. This involves a total of 7.2 million units of Benzathine Penicillin G, delivered as three separate 2.4 million unit injections given weekly for three consecutive weeks. The longer course is necessary because the bacteria divide more slowly in later stages, requiring prolonged exposure. If a patient misses a dose by more than nine days, the entire treatment sequence must be restarted.
Neurosyphilis Treatment
Neurosyphilis occurs when the infection spreads to the central nervous system. This requires a different approach because Benzathine Penicillin G poorly penetrates the brain and spinal fluid. Treatment involves Aqueous Crystalline Penicillin G, given intravenously (IV) for 10 to 14 days. This continuous IV administration ensures sufficient antibiotic concentration reaches the nervous system.
Addressing Treatment Complications and Alternatives
Not all patients can receive Penicillin G due to known allergies. For non-pregnant patients with a confirmed penicillin allergy, alternative antibiotics are available, though they are considered less optimal. Preferred alternatives for treating early syphilis include Doxycycline or Tetracycline, administered orally over 14 days.
For late latent syphilis or syphilis of unknown duration, the alternative treatment duration is extended to 28 days. These regimens are not safe for pregnant patients due to potential risks to the fetus. In these cases, the standard practice is penicillin desensitization, which safely allows the patient to receive the preferred Penicillin G treatment.
The Jarisch-Herxheimer reaction is an expected, non-allergic complication that can occur within hours of the first dose. This acute, temporary reaction is characterized by fever, headache, muscle aches, and sometimes an exacerbation of skin lesions. It is caused by the release of inflammatory molecules as the spirochetes are rapidly killed. This reaction usually resolves within 24 hours and is a sign that the treatment is successfully working, not a true drug allergy.
Monitoring Treatment Effectiveness
After the antibiotic course is completed, follow-up serologic testing confirms that the infection has been cured. These evaluations rely on quantitative nontreponemal tests, such as RPR or VDRL. The quantitative result, known as the titer, indicates the amount of antibody present and tracks the body’s response to the medication.
A successful outcome is defined by a sustained, four-fold drop in the nontreponemal test titer, equivalent to a reduction of at least two dilutions (e.g., 1:32 to 1:8). For early syphilis, this drop is expected within six to twelve months after treatment. For late latent syphilis, the response is slower, and the four-fold decline is monitored over 12 to 24 months.
Follow-up testing is typically scheduled at 6, 12, and 24 months post-treatment. If the titer fails to drop adequately or increases four-fold, it may indicate treatment failure or reinfection, requiring reevaluation and possibly retreatment. Some individuals may have a persistent low-level titer (serofast reaction) despite being cured, which usually does not require further treatment if no new symptoms are present.