Erythromycin may not prevent congenital syphilis in the baby. People who are allergic to penicillin should ideally be desensitized to it, and then treated with penicillin. Several hours after getting treatment for the early stages of syphilis, people may experience the Jarisch-Herxheimer reaction. This process is caused by an immune reaction to the breakdown products of the infection and not an allergic reaction to the antibiotic. Follow-up blood tests must be done at 3, 6, 12, and 24 months to ensure that the infection is gone.
Avoid sexual contact when the chancre is present. Use condoms until two follow-up tests have shown that the infection has been cured, to reduce the chance of transmitting the infection. All sexual partners of the person with syphilis should also be treated. Syphilis can spread very easily in the primary and secondary stages. Although secondary syphilis usually goes away within weeks, in some cases it may last for up to 1 year. Without treatment, up to one-third of people will have late complications of syphilis.
In addition, untreated secondary syphilis during pregnancy may spread the disease to the developing baby. This is called congenital syphilis. If you are sexually active, practice safer sex and always use a condom. Goldman-Cecil Medicine. Philadelphia, PA: Elsevier; chap Syphilis Treponema pallidum. Stary G, Stary A. Sexually transmitted infections. Updated by: Jatin M. Editorial team. In addition, gummas, granulomatous lesions with coagulated or amorphous centers, form most commonly in the skin, liver, bones, and spleen.
Both humoral and cell mediated immune responses are mounted against T. At all stages of infection, there are local cellular infiltrates consisting of lymphocytes, macrophages, and plasma cells at the sites of disease Cell mediated and humoral immune responses peak in secondary syphilis.
Spirochetes may remain alive and continue to replicate in immunologically sequestered sites in the body even with a brisk initial immune response and no outward clinical manifestations of disease in at least 1 of 4 persons who are not treated. In late latent syphilis, after many years of latency, treponemes begin to multiple and Th1 lymphocytes produce high levels of nitric oxide and IL instead of IL-2 and IFN This immunological escape by T.
First of all, it has a very slow dividing time of hours. Secondly, it has a scarcity of protruding antigenic proteins membrane proteins which make an antibody response more difficult. Thirdly, it has the ability to vary its antigens by gene conversion which may result in a subpopulation of T. Early susceptibility testing of various antibiotics against T.
Using the rabbit model, Eagle and co-workers in the 's found that established later stage disease required a longer course of therapy but cure could be accomplished with relatively low dose therapy 27 given over a prolonged period of time. These early studies have served as the basic tenants in our approach to syphilis therapy.
Penicillin, the first antibiotic developed, was the first known effective antibiotic for T. The maximally treponemicidal serum concentration of penicillin is 0. However, a concentration as low as 0. In the rabbit model, viable treponemes may persist in the lymph nodes even after early lesions have been cleared.
Resistance to penicillin has not yet been found among clinical isolates but there is the potential for the acquisition of extrachromosomally mediated antibiotic resistance since at least one strain has been shown to contain plasmid DNA Based on studies done with the time honored in vivo rabbit model, amoxicillin 82 , ceftriaxone 66 , ceftizoxime 65 , cefmetazole 3 and cefetamet 30 have been shown to be curative.
Macrolide antibiotics are also able to inhibit T. When erythromycin was directly compared to penicillin G for the treatment of rabbit skin syphilomas, a single injection of penicillin decreased the motile T. Only after multiple injections of erythromycin was the number of motile treponemes decreased in amounts similar to that of penicillin.
Azithromycin, which has the advantage of once daily dosing, also has activity against T. Thus macrolides are relegated to second line antibiotic treatment status.
Chloramphenicol, an antibiotic no longer available in the USA, has failed to eradicate infection in the rabbit model but has been successful in treating syphilis in humans Because it concentrates in the CNS, it has utility in treating neurosyphilis.
Spectinomycin 94 , the quinolone class of antibiotics , and clindamycin 6 have negligible activity against T. Combination therapy for syphilis is no more efficacious than single drug therapy. The addition of amoxicillin and probenecid for 10 days to 2. The following points are important to note before a discussion of antimicrobial therapy for syphilis.
First, as in the case of many infections, a natural immune response can clear T. Hence, antibiotics augment clearance and subsequent cure but do not guarantee it. Furthermore, the pharmacology of the antibiotic preparation must be considered, specifically whether it reliably reaches the CNS in adequate amounts to inhibit T.
Finally, the marker currently use to determine success of therapy, decrease in non-treponemal titers four-fold, is only indirect evidence of therapeutic success. Penicillin is the best studied and still remains the recommended therapy for syphilis Initial studies done in the rabbit model showed that the minimal inhibitory concentration that cures primary lesions is easily achieved with this dose of benzathine penicillin The original studies of penicillin treatment in humans were performed before the establishment of the standard double-blinded placebo or comparison controlled randomized clinical trials to evaluate the efficacy of therapy.
However, there are only a few randomized studies comparing penicillin to other antibiotics and only one study evaluating dosing schedules 1 , 2 , 18 , 37 , Rigorous studies of penicillin to evaluate dose, duration, and preparation of antibiotic that would achieve cure with minimal toxicity and cost are severely lacking. After nearly 75 years, there still remains much debate as to what dosing schedules and which preparations are appropriate for the various stages and types of persons infected with T.
Hence, all recommendations of treatment for syphilis must be regarded with a degree of skepticism. Because therapy should be tailored according to the benefit that a person will receive from a particular therapy balanced with the inconvenience and cost of alternative forms of therapy, the following discussion will focus on therapeutic options rather than rigorous recommendations. The CDC periodically reviews the recommended treatments for syphilis Table 3 The CDC treatment guidelines are based on the premise that different stages or forms of the disease should be treated with different preparations and doses of penicillin.
Following the principles of public health or population based guidelines; their goal is to provide therapeutic recommendations that will cure the greatest number of patients with minimal expense, easy administration, and high compliance In contrast, treatment of the individual patient rests with the treating clinician who must weigh the risk of failing to cure a curable disease.
Non-pregnant women and men with early syphilis, which includes primary syphilis the stage that occurs immediately after infection characterized by an ulcer or chancre ; secondary syphilis the later stage corresponding to spirochete dissemination and characterized by skin rash ; and early latent syphilis the stage up to one year after initial infection when positive serology's are the only indication of infection , should be treated intramuscularly with one injection of 2.
The CDC also recommends that non-pregnant women and men with late latent syphilis syphilis of more than 1-year in duration , latent syphilis of unknown duration, and tertiary syphilis except neurosyphilis also receive benzathine penicillin Table 2 but at an increased total dose of 7. Acknowledging the well-recognized fact the neurosyphilis is the most difficult manifestation to treat, the CDC recommends that persons with neurosyphilis be treated with 3 - 4 million units of aqueous crystalline penicillin G given intravenously every 4 hours million units daily for days.
However, who should be included in this classification of "neurosyphilis" is vague and ill defined. Patients with a reactive cerebrospinal fluid VDRL or RPR test are the easiest to classify and are accepted as definitely having neurosyphilis. But most patients have either no symptoms or ill-defined symptoms and most have nonspecific CSF abnormalities. Furthermore, despite the fact that T. In fact, the CDC discourages performing a lumbar puncture in early syphilis unless the patient has optic, auditory, cranial nerve, meningeal symptoms, or other indications of.
The rationale is that although early invasion of the CNS by T. Although benzathine penicillin is effective therapy for the vast majority of persons with syphilis, there are multiple reports of treatment failures, especially in patients co-infected with Human Immunodeficiency Virus HIV.
Although this failure can be at times attributed to re-infection 26, 31 , many of those cases are convincingly due to failure of initial therapy Some patients, especially those with HIV, will go on to develop late neurosyphilis in years. Unfortunately, the diagnosis is difficult to establish and penicillin therapy after the diagnosis of syphilis rarely reverses neurological deficits The clinician must weigh the risk of CNS invasion in each individual patient in deciding whether or not benzathine penicillin is adequate.
This assessment should take into account immunocompetent of the host and stage of disease. Since the most reliable form of treatment is one that is reaches treponemicidal levels in the CNS, the most reliable therapy for any form of syphilis in any type of patient is 3 - 4 million units of aqueous crystalline penicillin G given intravenously iv every 4 hours million units daily for days Table 3 since between 5 and 24 million units of intravenous penicillin G consistently achieves levels in the CSF that are treponemicidal 80, Hence, it would follow that treatment failures would be rare when compared to regimens that failed to reliably penetrate the CNS This regimen is the most likely to prevent late neurological deficits which is rarely reversed even after treatment.
However, it is rarely used even in immunocompromised patients except after neurological deficits have developed since inpatient hospital treatment is not always practical from a reimbursement or lifestyle perspective.
If outpatient therapy that achieved treponemicidal levels in the CNS is desired, 2. Treponemicidal levels of penicillin have not been achieved as reliably with procaine penicillin but supplementation with probenecid will achieve treponemicidal levels This option is uncommonly used since patient compliance is problematic because of the pain associated with repeated injections. The semi-synthetic penicillin, amoxicillin, when given with probenecid given 3.
Probenecid inhibits renal excretion of natural and semi- synthetic penicillins. As previously noted, amoxicillin is treponemicidal in the rabbit model, and when 2 gm of amoxicillin plus mg of probenecid is administered to fasting adults, the MIC for T. Clinical trials, albeit small, have confirmed the utility of this regimen 29 , 90 , The first- and third- generation cephalosporin antibiotics, in particular ceftriaxone, are also effective in treating syphilis.
Ceftriaxone has been recommended as an alternative for treatment of early disease and "might be effective for treating late latent syphilis or syphilis of unknown duration" Table 3 This drug is particularly attractive since it readily crosses the blood brain barrier. Both serum and CSF levels exceeding those needed to kill T. It has been used clinically to successfully to treat incubating syphilis 55 , primary syphilis 55 , 81 , 96 , , , secondary syphilis 55 , 96 , , latent syphilis 24 , and neurosyphilis 24 , 53 , However, there have been reports of treatment failures in HIV infected patients, similar to those found with benzathine penicillin 24 , 96 , Doxycycline mg twice daily is also an effective alternative for treatment of immunocompetent adults with syphilis.
Although there is limited data on late latent syphilis, doxycycline is another alternative but the course of therapy should be extended to 28 days The enthusiasm for this regimen is restrained because it is bacteriostatic in vitro and not bacteriocidal Furthermore tetracycline and doxycycline are contraindicated in pregnant women and children under the age of 8 because of potential damage to developing bones and teeth Other regimens that are less desirable because of poor CSF penetration and reports of resistance are the macrolide antibiotics.
Another macrolide, azithromycin, has been shown in a recent meta-analysis to be more effective than benzathine penicillin G for treating early syphilis 1. However, in addition to its probable inadequate penetration into the CSF , it has been associated with resistance and treatment failures and therefore it can only be recommended when there are no other alternatives 17 , 63 , 70 , 77 , 79 , 83 , 97 , , , If treatment is interrupted for more than 24 hours, then the full course of therapy is restarted.
Children diagnosed beyond the newborn period with congenital syphilis should also be treated presumptively for CNS involvement with therapy as described above except that aqueous crystalline penicillin needs to be administered every hours instead of every 8 or 12 hours Syphilitic involvement of the eye, a relatively common occurrence in HIV co-infected persons, should be treated with penicillin G 12 to 24 million units per day for 10 to 14 days regardless of CSF findings Penicillin, however, regardless of dose or preparation, does not easily achieve treponemicidal levels in anterior chamber of the eye and hence, requires high doses and prolonged treatment 14 days to improve the chances of adequate aqueous fluid levels Hence, it may also be prudent to consider chloramphenicol or cephalothin, antibiotics that do achieve adequate levels in the anterior chamber of the eye, as possible first line agents Because of excellent CNS penetration, chloramphenicol in a dose of 2 gm daily for 30 days is another alternative for optic syphilis.
As is the case of penetration into the anterior chamber of the eye, penicillin does not easily penetrate the labyrinth of the inner ear Hence, a neurosyphilis regimen is warranted. Patients are usually treated with a prolonged course of penicillin for six weeks to three months with the addition of steroids 16 , 23 , Oral prednisone mg daily or every other day for at least 7 to 8 days should be given as tolerated by the patient The utility of the steroids has never been proven but has become the standard of care to guard against the sudden worsening of hearing loss attendant to an acute reaction to released antigens form lysing organisms Jarish-Herxheimer Reaction.
Although treatment failures and progression to syphilis appear to be less common in HIV infected patients on effective antiretroviral therapy ART 40 , 41 , immunosuppression associated with HIV infection and its deleterious effect on syphilis outcomes has been well described. More florid clinical manifestations, including multiple and more frequent genital ulcers and symptomatic neurosyphilis, occurring early in the course of syphilis suggestive of a high spirochete burden 61 , have been well documented in persons co-infected with HIV.
In addition, multiple case reports suggest that HIV infected patients are more likely to fail antibiotic therapy than non-HIV infected patients 5 , 61 , 71 , For example, T. In addition, in a study of 59 patients with neurosyphilis, HIV infected patients were 2. Furthermore, unlike many treatment failures in immunocompetent hosts, these failures are more likely to be associated with clinical disease, especially neurosyphilis 22 , 24 , More florid clinical manifestations and the higher frequency of treatment failures are most likely due to immune dysfunction coincident with HIV that results in a significantly higher spirochete load.
There is a greater likelihood that spirochetes will remain active in sequestered sites. Treatment for syphilis is not necessarily benign. It is rarely seen in latent syphilis and occurs in varying amounts in the various forms of tertiary syphilis This reaction, called the Jarisch-Herxheimer reaction, is most commonly associated with penicillin therapy but also has been associated with other antibiotics used to treat syphilis 4.
It has been correlated with the release of heat stable "pyrogens" from T. The clinical course is marked by the abrupt onset of symptoms usually beginning within two hours, occasionally as late as 24 hours, after initiation of therapy 12 , Besides fever, clinical signs and symptoms may include chills, headache, nausea, vomiting, myalgias, tachycardia, hyperventilation, mild hypotension, vasodilatation with flushing, and the exacerbation and new onset of skin lesions It lasts hours and is generally safe and self-limited The exceptions are during the second half of pregnancy when there a risk of premature labor and fetal distress 12 and during cardiovascular, neurosyphilis and otosyphilis when reactions are more severe and can be life threatening Acetaminophen or aspirin can be used for symptomatic relief.
In severe cases or those associated with cardiovascular syphilis or neurosyphilis, prednisone 60 mg can be given. When given intravenously, this usually results in a prompt and dramatic decrease in fevers Since penicillin is the optimal therapy for syphilis, penicillin should be seriously considered even in patients with penicillin allergies, except in those with a history of Stevens-Johnson syndrome, or alternatives are limited.
These situations include syphilis in pregnant women, infants with congenital syphilis and adults with symptomatic neurosyphilis since treatment must be effective as soon as possible to prevent irreversible neurological disease. In addition, in syphilis in pregnancy and congenital syphilis, the toxicities associated with the tetracyclines make this option undesirable not only in terms of possible treatment failures but also in terms of damage to bone and teeth development In addition, the vast majority of patients who report a history of penicillin allergy will not have an allergic reaction upon re-challenge.
Anaphylactic reactions are extremely rare today. The most reliable method of distinguishing those who will have a future reaction from those who will not is skin testing. Prior to skin testing, patients should be instructed not to take antihistamines, tricyclic antidepressants, and adrenergic drugs within a time interval appropriate for the corresponding half-life of the medication For instance, chlorpheniramine maleate or terfenadine should not have been taken within 24 hours; diphenhydramine HCL or hydroxyzine within 4 days; and astemizole within 3 weeks.
Testing is begun by injecting skin test reagents, including a negative diluent and positive histamine controls, in the epidermis on the volar surface of the forearm with a 26 gauge needle without drawing blood If there is no reaction, then the same reagents are injected intradermally and if the diameter of induration is greater than 5 mm after 15 minutes, then the test is positive.
Optimally, skin testing should include diluents with both the major and minor determinants of penicillin Because minor determinants of penicillin are not commercially available in the U.
Although desensitization can be done both orally and intravenously, oral desensitization is probably safer and certainly less expensive and easier It should be performed in an intensive care setting with continuous electrocardiogram monitoring.
Doses of penicillin should be gradually increased until the dose required for therapy is achieved. One-third of patients will develop a transient allergic reaction during desensitization but it is usually mild and self-limited. If mild symptoms occur, then the dose of penicillin should be stabilized until there are no signs or symptoms. If it is more sever, such as hypotension, laryngeal edema, or asthma, then the dose should be reduced at least ten-fold.
There should be no interruption between desensitization and treatment since there the risk of an allergic reaction increases as the time from desensitization increases. As in any disease, the primary endpoint of therapy is clinical and a carefully taken medical history, physical exam and appropriate laboratory tests will determine if therapy has been successful.
In primary syphilis, the patient should be examined for resolution of the chancre; in secondary syphilis, for resolution of the skin rash and any of the other protean disease manifestations that the patient may experience; and in early neurosyphilis for resolution of signs and symptoms of neurological disease. In late neurosyphilis, there is usually no reversal of signs and symptoms that are present prior to therapy but patients should be monitored carefully for further progression of disease.
During any stage of syphilis and at any time, if there is persistence or recurrence of clinical disease, the person should be retreated. He or she should also be questioned about the possibility of re-infection to ease the concern about antibiotic resistance. However, since the disease process is clinically silent at many stages and we are unable to grow in routine culture, it is necessary to follow disease activity with surrogate markers of infection.
Treponemal antibody tests such as the FTA-abs are not helpful for measuring response to therapy since they are not quantified, usually remain positive for life, and do not correlate with disease activity , In contrast, nontreponemal tests such as the RPR and VDRL are quantifiable, revert to negative in the vast majority of patients given effective therapy, and do correlate with disease activity.
Fiumara found that all patients with treated primary syphilis had non-reactive RPR titers at one year 31 and all patients with treated secondary syphilis by two years However, some studies have shown that low but positive titer VDRL or RPR tests of or less may persist despite no other evidence of treatment failure the "serofast reaction" 12 , This may represent a false positive result or, especially when the titer is , persistent active infection or reinfection A fourfold change in titers, equivalent to a two dilution change, is considered a significant change and implies a change in disease activity.
For instance, a change from to is significant while a change from to is not. The frequency of obtaining serological testing after treatment depends on the stage of disease and characteristics of the patients. Non-HIV infected adults with syphilis should be tested at three, six, and twelve months If syphilis is greater than one year in duration or of unknown duration, then serologic testing should also be checked at 24 months.
Pregnant women who are infected should have follow up serology in the third trimester and at delivery If a pregnant woman is at a high risk for re-infection or in an area where the prevalence of syphilis is high, she should be retested every month Infants with congenital syphilis and those who are sero-positive only because of passive transfer of maternal antibodies and are not infected should be checked with serological testing every two to three months The rate of decline after treatment of nontreponemal titers appears to be related to the stage of disease, height of the initial titers, and a prior history of syphilis 7 , 31 , 32 , 33 , Brown and co-workers found a fourfold decrease in RPR titers at 6 months and eightfold decrease at 12 months in successfully treated patients with primary and secondary syphilis but there was a slower decline in patients with early latent disease and longer duration of symptoms 7.
In contrast, patients with no prior history of syphilis re-infection have a more rapid decline in titers 7 , 31 , 32 , In addition, patients with macular rashes during the secondary stage revert to negative quicker than those with papular rashes In adequately treated congenital syphilis, titers should decline by three months of age and should be non-reactive by six months of age Titers, however, may decline slower if treatment is not initiated in the neonatal period and, occasionally, titers are still positive up to one year after birth.
If titers are found to be stable or increasing or are still present after one year of age, then the child should be re-evaluated fully, including a CSF examination, and retreated. Besides following serum nontreponemal test, a lumbar puncture is recommended every six months after treatment for neurosyphilis, including infants with abnormal CSF analyses, until the pleocytosis has resolved or CNS nontreponemal antibodies disappear If the CSF cell count is not decreased by six months or remains abnormal two years after therapy, re-treatment is indicated 8.
Although HIV infected patients may have similar non-treponemal VDRL and RPR response as non-HIV infected persons 43 , 49 , HIV infected patients are more prone to have a delayed serological response to infection or therapy and greater likelihood of having persistently reactive non-treponemal titers after treatment Furthermore, HIV infected patients are more likely to have high non-treponemal antibody titers in secondary syphilis, e. This abnormal response to therapy is most likely due to immune dysfunction related to the increased polyclonal B cell activation found in HIV infection rather than a true change in disease activity, although the resultant loss of effective T-cell function could result in less ability to clear the spirochete Obviously, the most effective prophylaxis against contracting syphilis is avoidance of sexual contact with persons who harbor the spirochete.
Condoms use during sexual intercourse can also be inferred to be protective from studies of HIV infection. Currently, prophylactic drugs are not recommendations in any group of patients with syphilis except those who have been exposed to a person with syphilis and in this population, it is unclear whether medicines prevent infection or treat very early disease, e.
We recommend that persons sexually exposed to primary, secondary, or latent syphilis of less than 1- year's duration within the previous 90 days be treated for syphilis even if they have negative serological tests for syphilis because there is data to suggest that therapy is most successful when initiated early and the treponemal burden is relatively low Treatment with 2.
Transmission occurs only when mucocutaneous lesions are present, which is usually within one year after initial infection , so contact with persons with syphilis greater than one year in duration is not an immediate indication for treatment Instead, it is recommended that these persons be followed clinically and serologically for syphilis. Persons with exposure greater than 90 days prior to evaluation need not have immediate treatment, unless they have positive serological test, serological results will be delayed or follow up is uncertain.
Blood transmission is rare today because of the low incidence of disease and blood storage procedures. Azithromycin vs.
Cochrane Database Syst Rev. Syphilis may also damage heart valves. Adults with sexually transmitted syphilis or other genital ulcers have an estimated two- to fivefold increased risk of contracting HIV. A syphilis sore can bleed easily, providing an easy way for HIV to enter the bloodstream during sexual activity. If you're pregnant, you may pass syphilis to your unborn baby. Congenital syphilis greatly increases the risk of miscarriage, stillbirth or your newborn's death within a few days after birth.
There is no vaccine for syphilis. To help prevent the spread of syphilis, follow these suggestions:. If tests show that you have syphilis, your sex partners — including current partners and any other partners you've had over the last three months to one year — need to be informed so that they can get tested.
If they're infected, they can then be treated. Official, confidential partner notification can help limit the spread of syphilis. The practice also steers those at risk toward counseling and the right treatment.
And since you can contract syphilis more than once, partner notification reduces your risk of getting reinfected.
People can be infected with syphilis and not know it. In light of the often deadly effects syphilis can have on unborn children, health officials recommend that all pregnant women be screened for the disease. Mayo Clinic does not endorse companies or products. Advertising revenue supports our not-for-profit mission. This content does not have an English version.
This content does not have an Arabic version. Overview Syphilis is a bacterial infection usually spread by sexual contact.
Primary syphilis Open pop-up dialog box Close. Primary syphilis Primary syphilis causes painless sores chancres on the genitals, rectum, tongue or lips. Request an Appointment at Mayo Clinic. Share on: Facebook Twitter. Show references Syphilis — CDC fact sheet detailed. Centers for Disease Control and Prevention. Accessed July 14, Hicks CB, et al. Syphilis: Epidemiology, pathophysiology, and clinical manifestations in HIV-uninfected patients.
Merck Manual Professional Version. Syphilis: Treatment and monitoring. Syphilis: Screening and diagnostic testing. Syphilis — CDC fact sheet. Accessed July 30, Jameson JL, et al.
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