For neurosyphilis, due to the poor penetration of benzylpenicillin into the central nervous system, those affected are recommended to be given large doses of intravenous penicillin for a minimum of 10 days. If a person is allergic, ceftriaxone may be used or penicillin desensitization attempted. Other late presentations may be treated with once-weekly intramuscular benzylpenicillin for three weeks. If allergic, as in the case of early disease, doxycycline or tetracycline may be used, albeit for a longer duration. Treatment at this stage limits further progression but has only slight effect on damage which has already occurred.

One of the potential side effects of treatment is the Jarisch-Herxheimer reaction. It frequently starts within one hour and lasts for 24 hours, with symptoms of fever, muscle pains, headache, and a fast heart rate. It is caused by cytokines released by the immune system in response to lipoproteins released from rupturing syphilis bacteria.

The Jarisch-Herxheimer reaction, which is the response to the body after endotoxins are released by the death of harmful organisms in the human body, starts usually during the first day of antibiotic treatment. The reaction increases the person's body temperature, decreases the overall blood pressure (both systolic and diastolic levels), and results in leukopenia and rigors in the body. This reaction can occur during any treatment of spirochete diseases.

It is important to realize that syphilis can recur. An individual who has had the disease once, even if it has been treated, does not prevent the person from experiencing recurrence of syphilis. Individuals can be re-infected, and because syphilis sores can be hidden, it may not be obvious that the individual is infected with syphilis. In these cases, it is vital to become tested and treated immediately to reduce spread of the infection.

If a pregnant mother is identified as being infected with syphilis, treatment can effectively prevent congenital syphilis from developing in the fetus, especially if he or she is treated before the sixteenth week of pregnancy. The fetus is at greatest risk of contracting syphilis when the mother is in the early stages of infection, but the disease can be passed at any point during pregnancy, even during delivery (if the child had not already contracted it). A woman in the secondary stage of syphilis decreases her fetus's risk of developing congenital syphilis by 98% if she receives treatment before the last month of pregnancy. An afflicted child can be treated using antibiotics much like an adult; however, any developmental symptoms are likely to be permanent.

Kassowitz’s law is an empirical observation used in context of congenital syphilis stating that the greater the duration between the infection of the mother and conception, the better is the outcome for the infant. Features of a better outcome include less chance of stillbirth and of developing congenital syphilis.

The Centers for Disease Control and Prevention recommends treating symptomatic or babies born to infected mother with unknown treatment status with procaine penicillin G, 50,000 U/kg dose IM a day in a single dose for 10 days. Treatment for these babies can vary on a case by case basis. Treatment cannot reverse any deformities, brain, or permanent tissue damage that has already occurred.

The most popular treatment forms for any type of syphilis uses penicillin, which has been an effective treatment used since the 1940s.

Other forms also include Benzathine penicillin, which is usually used for primary and secondary syphilis (it has no resistance to penicillin however). Benzathine penicillin is used for long acting form, and if conditions worsen, penicillin G is used for late syphilis.

In the case of rape, the person can be treated prophylacticly with antibiotics.

An option for treating partners of patients (index cases) diagnosed with chlamydia or gonorrhea is patient-delivered partner therapy, which is the clinical practice of treating the sex partners of index cases by providing prescriptions or medications to the patient to take to his/her partner without the health care provider first examining the partner.

Some vertically transmitted infections, such as toxoplasmosis and syphilis, can be effectively treated with antibiotics if the mother is diagnosed early in her pregnancy. Many viral vertically transmitted infections have no effective treatment, but some, notably rubella and varicella-zoster, can be prevented by vaccinating the mother prior to pregnancy.

If the mother has active herpes simplex (as may be suggested by a pap test), delivery by Caesarean section can prevent the newborn from contact, and consequent infection, with this virus.

IgG antibody may play crucial role in prevention of intrauterine infections and extensive research is going on for developing IgG-based therapies for treatment and vaccination.

The treatment of TORCH syndrome is mainly supportive and depends on the symptoms present; medication is an option for herpes and cytomegalovirus infections.

The CDC recommendation for chancroid is a single oral dose (1 gram) of azithromycin, or a single IM dose of ceftriaxone, or oral erythromycin for seven days.

Abscesses are drained.

"H. ducreyi" is resistant to sulfonamides, tetracyclines, penicillins, chloramphenicol, ciprofloxacin, ofloxacin, trimethoprim and aminoglycosides. Recently, several erythromycin resistant isolates have been reported.

Treatment failure is possible with HIV co-infection and extended therapy is sometimes required.

Penicillin is used to treat neurosyphilis; however, early diagnosis and treatment is critical. Two examples of penicillin therapies include:

- Aqueous penicillin G 3–4 million units every four hours for 10 to 14 days.

- One daily intramuscular injection and oral probenecid four times daily, both for 10 to 14 days.

Follow-up blood tests are generally performed at 3, 6, 12, 24, and 36 months to make sure the infection is gone. Lumbar punctures for CSF fluid analysis are generally performed every 6 months.

Neurosyphilis was almost at the point being unheard of in the United States after penicillin therapy was introduced. However, concurrent infection of "T. pallidum" with human immunodeficiency virus (HIV) has been found to affect the course of syphilis. Syphilis can lie dormant for 10 to 20 years before progressing to neurosyphilis, but HIV may accelerate the rate of the progress. Also, infection with HIV has been found to cause penicillin therapy to fail more often. Therefore, neurosyphilis has once again been prevalent in societies with high HIV rates and limited access to penicillin. Blood testing for syphilis was once required in order to obtain a marriage license in most U.S. states, but that requirement has been discontinued by all 50 states over recent years, also contributing to the spread of the disease.

Prognosis is excellent with proper treatment. Treating sexual contacts of affected individual helps break cycle of infection.

Researchers had hoped that nonoxynol-9, a vaginal microbicide would help decrease STI risk. Trials, however, have found it ineffective and it may put women at a higher risk of HIV infection.

TORCH syndrome can be prevented by treating an infected pregnant person, thereby preventing the infection from affecting the fetus.

Death from congenital syphilis is usually due to bleeding into the lungs.

Neonatal infection treatment is typically started before the diagnosis of the cause can be confirmed.

Neonatal infection can be prophylactically treated with antibiotics. Maternal treatment with antibiotics is primarily used to protect against group B streptococcus.

Women with a history of HSV, can be treated with antiviral drugs to prevent symptomatic lesions and viral shedding that could infect the infant at birth. The antiviral medications used include acyclovir, penciclovir, valacyclovir, and famciclovir. Only very small amounts of the drug can be detected in the fetus. There are no increases in drug-related abnormalities in the infant that could be attributed to acyclovir. Long-term effects of antiviral medications have not been evaluated for their effects after growth and development of the child occurs. Neutropenia can be a complication of acyclovir treatment of neonatal HSV infection, but is usually transient. Treatment with immunoglobulin therapy has not been proven to be effective.

The disease can be treated with penicillin, tetracycline (not to be used in pregnant women), azithromycin or chloramphenicol, and can be prevented through contact tracing by public health officials. A single intramuscular injection of long-acting penicillin is effective against endemic treponematoses including pinta, yaws, and bejel

Each type of vertically transmitted infection has a different prognosis. The stage of the pregnancy at the time of infection also can change the effect on the newborn.

It is treatable with penicillin or other antibiotics, resulting in a complete recovery.

To reduce neonatal infection, routine screening of pregnant women for HIV, hepatitis B, syphilis, and rubella susceptibility is required in the UK.

Treatment with an vaginal antibiotic wash prior to birth does not prevent infection with group B streptococcus bacteria. Breast milk protects against necrotizing enterocolitis.

Because GBS bacteria can colonize the lower reproductive tract of 30% of women, typically pregnant women are tested for this pathogen from 35 to 37 weeks of pregnancy. Before delivery treatment of the mother with antibiotics reduces the rate of neonatal infection. Prevention of the infection of the baby is done by treating the mother with penicillin. Since the adoption of this prophylatic treatment, infant mortality from GBS infection has decreased by 80%.

Mothers with symptomatic HSV and who are treated with antiviral prophylaxis are less prone to have an active, symptomatic case at the time of birth and it may be able to reduce the risk of passing on HSV during birth. Cesarean delivery reduces the risk of infection of the infant.

Intravenously administered penicillin is the treatment of choice. Associated pain can be treated with opiates, valproate, or carbamazepine. Those with tabes dorsalis may also require physical therapy to deal with muscle wasting and weakness. Preventive treatment for those who come into sexual contact with an individual with syphilis is important.

Bejel, or endemic syphilis, is a chronic skin and tissue disease caused by infection by the "endemicum" subspecies of the spirochete "Treponema pallidum".

Bejel is also known by a variety of other names, including belesh, dichuchwa, endemic syphilis, nonvenereal syphilis, frenga, njovera, skerljevo, siti, or treponematosis-bejel type.

Pregnancy does not have an adverse effect on the course of Behçet's disease and may possibly ameliorate its course. Still, there is a substantial variability in clinical course between patients and even for different pregnancies in the same patient. Also, the other way around, Behçet's disease confers an increased risk of pregnancy complications, miscarriage and Cesarean section.

A chancre ( ) is a painless ulceration (sore) most commonly formed during the primary stage of syphilis. This infectious lesion forms approximately 21 days after the initial exposure to "Treponema pallidum", the gram-negative spirochaete bacterium yielding syphilis. Chancres transmit the sexually transmissible disease of syphilis through direct physical contact. These ulcers usually form on or around the anus, mouth, penis, and vagina. Chancres may diminish between four and eight weeks without the application of medication.

Chancres, as well as being painless ulcerations formed during the primary stage of syphilis, are associated with the African trypanosomiasis sleeping sickness, surrounding the area of the tsetse fly bite.

Pinta (also known as Azul, Carate, Empeines, Lota, Mal del Pinto and Tina) is a human skin disease endemic to Mexico, Central America, and South America caused by infection with a spirochete, "Treponema pallidum carateum", which is morphologically and serologically indistinguishable from the bacterium that causes syphilis.

Left untreated, tabes dorsalis can lead to paralysis, dementia, and blindness. Existing nerve damage cannot be reversed.