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Antibiotics for Syphilis

Examples

Penicillin is the antibioticClick here to see more information. most commonly used to treat syphilisClick here to see more information.. Penicillin is usually given as a shot (injection).
If you are allergic to penicillin, your doctor may prescribe another antibiotic in early stages of syphilis, such as doxycycline, tetracycline, ceftriaxone, or azithromycin. Or he or she may desensitize you so that you can safely take penicillin. Later stages of syphilis may require treatment with penicillin.
Penicillin is the only antibiotic that should be used during pregnancy. If you are pregnant and think you may be allergic to penicillin, discuss your allergy with your doctor.

How It Works

Antibiotics destroy the bacteria that cause syphilis.

Why It Is Used

Antibiotics are needed if you have a positive blood test for syphilis during routine screening or have symptoms suggestive of syphilis. Exposed sex partners of a person with syphilis and babies born to women who have syphilis also need treatment.
The amount of antibiotics used and how often the medicine is taken are based on the stage of the illness. For example, if neurosyphilis is present, you will need to receive antibiotics for 10 days to 2 weeks.

How Well It Works

Treatment with penicillin cures most cases of syphilis in any stage. Antibiotics prevent further complications of syphilis but may not reverse damage that has already occurred.
A follow-up exam and a blood test for cure should be done at 6 and 12 months after the antibiotics are given (and may be done at 24 months after latent syphilis) to be sure the infection is cured.
If human immunodeficiency virus (HIVClick here to see more information.) infection was also present at the time of treatment, follow-up exams and blood tests should be done at 3, 6, 9, 12, and 24 months.1
Syphilis passed to a baby from the mother (congenital syphilis) may be prevented if the woman is treated before the 16th to 18th weeks of her pregnancy. Treatment after 16 to 18 weeks will cure the infection and stop the damage to the baby. But it may not reverse damage already caused by the infection.

Side Effects

All medicines have side effects. But many people don't feel the side effects, or they are able to deal with them. Ask your pharmacist about the side effects of each medicine you take. Side effects are also listed in the information that comes with your medicine.
Here are some important things to think about:
  • Usually the benefits of the medicine are more important than any minor side effects.
  • Side effects may go away after you take the medicine for a while.
  • If side effects still bother you and you wonder if you should keep taking the medicine, call your doctor. He or she may be able to lower your dose or change your medicine. Do not suddenly quit taking your medicine unless your doctor tells you to.
Call 911 or other emergency services right away if you have:
  • Trouble breathing.
  • Swelling of your face, lips, tongue, or throat.
Call your doctor if you have:
  • Hives.
  • Severe belly pain or cramps.
  • Decreased urine.
  • Depression.
  • Nausea or vomiting.
  • Unusual bleeding or bruising.
Common side effects of this medicine include:
  • Diarrhea.
  • Headache.
  • Sore mouth or tongue.
  • Vaginal itching or discharge.
A Jarisch-Herxheimer reaction is a fairly common reaction to antibiotic treatment of syphilis that involves fever and headache. It may occur up to 8 hours after the first treatment of early syphilis. The reason the Jarisch-Herxheimer reaction occurs is not clear. But it may be caused by the toxins released from the syphilis bacteria as they are destroyed by antibiotics. A Jarisch-Herxheimer reaction is not the same as an allergic reaction to penicillin.
See Drug Reference for a full list of side effects. (Drug Reference is not available in all systems.)

What To Think About

Antibiotic treatment can cure syphilis. And it can prevent complications. The complications of tertiary-stage or congenital syphilis may not be reversed with treatment. But the progression of the disease will be stopped.
Penicillin is the preferred drug for treating syphilis. And penicillin is the standard therapy for the treatment of neurosyphilis, congenital syphilis, or syphilis acquired or detected during pregnancy. But other antibiotics (such as ceftriaxone) may be used.

Taking medicine

Medicine is one of the many tools your doctor has to treat a health problem. Taking medicine as your doctor suggests will improve your health and may prevent future problems. If you don't take your medicines properly, you may be putting your health (and perhaps your life) at risk.
There are many reasons why people have trouble taking their medicine. But in most cases, there is something you can do. For suggestions on how to work around common problems, see the topic Taking Medicines as Prescribed.

Advice for women

If you are pregnant, breast-feeding, or planning to get pregnant, do not use any medicines unless your doctor tells you to. Some medicines can harm your baby. This includes prescription and over-the-counter medicines, vitamins, herbs, and supplements. And make sure that all your doctors know that you are pregnant, breast-feeding, or planning to get pregnant.

Checkups

Follow-up care is a key part of your treatment and safety. Be sure to make and go to all appointments, and call your doctor if you are having problems. It's also a good idea to know your test results and keep a list of the medicines you take.
Complete the new medication information form (PDF)Click to view external link(What is a PDFClick here to see more information. document?) to help you understand this medication.

References

Citations

  1. Centers for Disease Control and Prevention (2010). Syphilis section of Sexually transmitted diseases treatment guidelines, 2010. MMWR, 59(RR-12): 1–110. Available online: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5912a1.htm?s_cid=rr5912a1_w.



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Diagnosis

Syphilis can be diagnosed by testing samples of:
  • Blood. Blood tests can confirm the presence of antibodies that the body produces to fight infection. The antibodies to the bacteria that cause syphilis remain in your body for years, so the test can be used to determine a current or past infection.
  • Cerebral spinal fluid. If it's suspected that you have nervous system complications of syphilis, your doctor may also suggest collecting a sample of cerebrospinal fluid through a procedure called a lumbar puncture (spinal tap).
Through the Centers for Disease Control and Prevention, your local health department offers partner services, which will help you notify your sexual partners that they may be infected. That way, your partners can be tested and treated and the spread of syphilis can be curtailed.

Treatment

When diagnosed and treated in its early stages, syphilis is easy to cure. The preferred treatment at all stages is penicillin, an antibiotic medication that can kill the organism that causes syphilis. If you're allergic to penicillin, your doctor will suggest another antibiotic.
A single injection of penicillin can stop the disease from progressing if you've been infected for less than a year. If you've had syphilis for longer than a year, you may need additional doses.
Penicillin is the only recommended treatment for pregnant women with syphilis. Women who are allergic to penicillin can undergo a desensitization process that may allow them to take penicillin. Even if you're treated for syphilis during your pregnancy, your newborn child should also receive antibiotic treatment.
The first day you receive treatment you may experience what's known as the Jarisch-Herxheimer reaction. Signs and symptoms include a fever, chills, nausea, achy pain and headache. This reaction usually doesn't last more than one day.

Treatment follow-up

After you're treated for syphilis, your doctor will ask you to:
  • Have periodic blood tests and exams to make sure you're responding to the usual dosage of penicillin
  • Avoid sexual contact until the treatment is completed and blood tests indicate the infection has been cured
  • Notify your sex partners so that they can be tested and get treatment if necessary
  • Be tested for HIV infection

Test ID: TPPA    
Syphilis Antibody by TP-PA, Serum


Useful For 

An aid to resolve discrepant results between screening treponemal (eg, enzyme immunoassay [EIA], multiplex flow immunoassay) and nontreponemal (eg, rapid plasma regain) assays

Testing Algorithm 

See Syphilis Serology Algorithm in Special Instructions.

Clinical Information 

Syphilis is a disease caused by infection with the spirochete Treponema pallidum. The infection is systemic and the disease is characterized by periods of latency. These features, together with the fact that T pallidum cannot be isolated in culture, mean that serologic techniques play a major role in the diagnosis and follow-up of treatment for syphilis.

Syphilis is categorized by an early primary infection in which patients may have non-specific symptoms, and potentially, genital lesions. Patients tested by serology during the primary phase may be negative for antibodies, especially if testing is performed during the first 1 to 2 weeks after symptom onset. As the disease progresses into the secondary phase, antibodies to T pallidum reach peak titers, and may persist indefinitely regardless of the disease state or prior therapy. Therefore, detection of antibodies to nontreponemal antigens, such as cardiolipin (a lipoidal antigen released by host cells damaged by T pallidum) may help to differentiate between active and past syphilis infection. Nontreponemal antibodies are detected by the rapid plasma reagin (RPR) assay, which is typically positive during current infection and negative following treatment or during late/latent forms of syphilis.

For prenatal syphilis screening, the syphilis IgG test (SYPGN / Syphilis Antibody, IgG, Serum) is recommended. Testing for IgM-class antibodies to T pallidum should not be performed during routine pregnancy screening unless clinically indicated.

Historically, the serologic testing algorithm for syphilis included an initial nontreponemal screening test, such as the RPR or the venereal disease research laboratory (VDRL) tests. Because these tests measure the host's antibody response to nontreponemal antigens, they may lack specificity. Therefore, a positive result by RPR or VDRL requires confirmation by a treponemal-specific test, such as the fluorescent treponemal antibody-absorbed (FTA-ABS) or the T pallidum particle agglutination (TP-PA). Although the FTA-ABS and TP-PA are technically simple to perform, they are labor intensive and require subjective interpretation by testing personnel.

Due to the low prevalence of syphilis in the United States, the increased specificity of treponemal assays, and the objective interpretation of automated treponemal enzyme immunoassay (EIA) and multiplex flow immunoassays (MFI), many large clinical laboratories have switched to screening for syphilis using a reverse algorithm. Per this algorithm, serum samples are first tested by an automated treponemal assay (eg, EIA or MFI). Specimens testing positive by these assays are then reflexed to the RPR assay to provide an indication of the patient's disease state and history of treatment. Recently, the Centers for Disease Control and Prevention recommended that specimens testing positive by a screening treponemal assay and negative by RPR be tested by a second treponemal test (eg, TP-PA). The results of TP-PA assist in determining whether the results of a screening treponemal test are truly or falsely positive.

Reference Values 

Negative

Interpretation 

Syphilis screening at Mayo Clinic is performed by using the reverse algorithm, which first tests sera for Treponema pallidum specific IgG antibodies using an automated multiplex flow immunoassay (MFI).(3) IgG antibodies to syphilis can remain elevated despite appropriate antimicrobial treatment and a reactive result does not distinguish between recent or past infection. To further evaluate disease and treatment status, samples that are reactive by the syphilis IgG screening test are reflexed to the rapid plasma reagin (RPR) assay, which detects antibodies to cardiolipin, a lipoidal antigen released from host cells damaged by T pallidum.(2) Unlike treponemal-specific antibodies, RPR titers decrease and usually become undetectable following appropriate treatment and can be used to monitor response to therapy.

In some patients, the results of the treponemal screening test (syphilis IgG) and RPR may be discordant (eg, syphilis IgG positive and RPR negative). To discriminate between a falsely reactive screening result and past syphilis, the Centers for Disease Control and Prevention recommends performing a second treponemal-specific antibody test using a method that is different from the initial screening test (eg, T pallidum particle agglutination; TP-PA).(2)

In the setting of a positive syphilis IgG screening result and a negative RPR, a positive TP-PA result is consistent with either 1) past, successfully treated syphilis, 2) early syphilis with undetectable RPR titers, or 3) late/latent syphilis in patients who do not have a history of treatment for syphilis. Further historical evaluation is necessary to distinguish between these scenarios (Table 1).

In the setting of a positive syphilis IgG screening result and a negative RPR, a negative TP-PA result is most consistent with a falsely reactive syphilis IgG screen (Table 1). If syphilis remains clinically suspected, a second specimen should be submitted, order SYGR / Syphilis IgG Antibody with Reflex, Serum.

Table 1. Interpretation and follow-up of reverse screening results
Patient history Test and result Interpretation Follow-up
EIA/CIA/MFI RPR TP-PA
Unknown history of syphilis Non-reactive N/A N/A No serologic evidence of syphilis None, unless clinically indicated  (eg, early syphilis)
Unknown history of syphilis Reactive Reactive N/A Untreated or recently treated syphilis See CDC treatment guidelines 
Unknown history of syphilis Reactive Non-reactive Non-reactive Probable false-positive screening test No follow-up testing, unless clinically indicated
Unknown history of syphilis Reactive Non-reactive Reactive Possible syphilis (eg, early or latent) or previously treated syphilis Historical and clinical evaluation required
Known history of syphilis Reactive Non-reactive Reactive or N/A Past, successfully treated syphilis None
CIA, chemiluminescence immunoassay; EIA, enzyme immunoassay; MFI, multiplex flow immunoassay; N/A, not applicable; RPR, rapid plasma reagin; TP-PA, Treponema pallidum particle agglutination.
http://www.cdc.gov/std/treetment/2010/

Cautions 

Testing by only Treponema pallidum particle agglutination (TP-PA) is not recommended for general screening purposes for syphilis. TP-PA should only be requested when:
1. The results of a treponemal screening test (eg, enzyme immunoassay [EIA] or multiplex flow immunoassay; MFI) and rapid plasma reagin (RPR) are discordant (eg, syphilis IgG-positive, RPR-negative)
2. A laboratory screens for syphilis using RPR and is in need of a treponemal confirmatory test.

Interpretation of results obtained with the Serodia TP-PA syphilis antibody test must be used in conjunction with the patient's clinical symptoms, medical history and other clinical and laboratory findings.

Serodia TP-PA assay is less sensitive than the fluorescent treponemal antibody absorption (FTA-ABS) test in untreated primary syphilis but compares favorably in all other stages of syphilis.

Serodia TP-PA assay should not be used to evaluate response to therapy since treponemal tests tend to remain reactive following treatment for syphilis.

Serodia TP-PA assay may be reactive in a small percentage (<1%) of normal or healthy persons. These false-positive results are often transient with unknown cause. False-positive results may occur in association with other underlying illnesses.

Serodia TP-PA may be reactive in persons from areas endemic for yaws or pinta.

Serodia TP-PA performs best in populations at risk for T pallidum infection.

False-positive or inconclusive results for this assay may be seen in patients with HIV, leprosy, toxoplasmosis, or Helicobacter pylori.

Supportive Data

Accuracy:
The Treponema pallidum particle agglutination (TP-PA) assay was compared to the BioPlex 2200 syphilis IgG multiplex flow immunoassays (MFI) assay using 1,200 serum specimens (1,100 prospective and 100 previously characterized sera). The results are summarized in Table 2:

Table 2. Comparison of the BioPlex 2200 syphilis IgG and TP-PA assays using serum samples (n=1,200)


BioPlex syphilis IgG MFI assay
Fujirebio
TP-PA

Positive Negative No result
Positive 101 3 0
Negative 11 1083 1
Indeterminate 0 1 0

Sensitivity = 90.18%; (95% confidence interval, 83.15%-94.61%)
Specificity = 99.6%; (95% confidence interval, 99.0%-99.9%)
Overall percent agreement = 98.7%; (95% confidence interval, 96.3%-100%)

All discrepant samples tested negative by rapid plasma reagin (RPR)

Precision:
For interassay precision, 1 negative (TP-PA titer <1:80), 1 low-positive (1:80), 1 mid-positive (1:320), and 1 high-positive (1:1280) serum specimen were tested by TP-PA over 10 separate days and showed 100% agreement with the expected result for each category of results.

For intraassay precision, a negative, low-positive, and high-positive serum specimen were tested 20 times in a single run and showed 100% agreement for each category of results.

Reference Range:
The expected result is negative for this test. To validate reference range, testing of sera collected from 50 healthy blood donors showed a reactive rate of 2% (1/50) by TP-PA. The positive sample was also determined to be positive by the BioPlex syphilis IgG assay.


Reportable Range:
The TP-PA is reported as positive, negative, or indeterminate.

Analytic Specificity:
Testing of sera (n=58) known to be positive for antibodies to other microorganisms/conditions (n =30) or from pregnant females (n=28) showed a positive rate of 0% (0/58) by TP-PA. See Table 3 for a list of samples included in the cross-reactivity panel.

Table 3. Cross-reactivity panel tested by TP-PA to assess analytical specificity

Antibody or condition tested: Number of samples tested by TP-PA
Epstein Barr VCA IgG 5
Epstein Barr VCA IgM 5
HSV IgG 5
HSV IgM 2
Lyme IgM/IgG 5
Heterophile antibody 5
Rheumatoid factor 3
Pregnancy 28

Clinical Reference 

1. Tramont EC: Treponema pallidum (Syphilis). In Principles and Practice of Infectious Diseases. Fifth edition. Edited by GL Mandell, JE Bennet, R Dolin. New York Churchill Livingstone, 2000, pp 2474-2491
2. CDC. Discordant results from reverse sequence syphilis screening-five laboratories, United States, 2006-2010. MMWR Morb Mortal Wkly Rep 2011;60(5):133-137
3. Binnicker MJ, Jespersen DJ, Rollins LO: Direct comparison of the traditional and reverse syphilis screening algorithms in a population with a low prevalence of syphilis. J Clin Microbiol 2012 Jan;50(1):148-150

Special Instructions