eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease

Syphilis: Treatment & Medication

Author: Muhammad Waseem, MD, Associate Professor of Emergency Medicine in Clinical Pediatrics, Weill Medical College of Cornell University; Consulting Staff, Department of Pediatrics, Bronx Lebanon Hospital; Consulting Staff, Department of Emergency Medicine, Lincoln Medical and Mental Health Center
Coauthor(s): Muhammad Aslam, MD, Instructor in Pediatrics, Harvard Medical School; Staff Physician, Department of Medicine/ Division of Newborn Medicine, Children's Hospital Boston
Contributor Information and Disclosures

Updated: Jul 28, 2009

Treatment

Medical Care

Penicillin remains the drug of choice (DOC) to treat all stages of syphilis; no evidence suggests an increasing penicillin resistance. Primary, secondary, and early latent diseases are treated with a single intramuscular (IM) dose of benzathine penicillin G (50,000 U/kg; not to exceed 2.4 million U). Although other regimens can be considered in patients with a penicillin allergy, desensitization followed by penicillin is the most preferred method. In patients with primary syphilis, doxycycline and tetracycline have shown a high serological treatment success rate, comparable to penicillin.8 Azithromycin has also demonstrated a high cure rate in a long-term follow-up.9

Patients who are allergic to penicillin and do not have neurosyphilis and are not pregnant may be treated with either doxycycline (100 mg oral [PO] bid for 2 wk) or tetracycline (500 mg PO qid for 2 wk). Shorter-acting forms of penicillin must be used to treat neurosyphilis to produce reliably therapeutic levels in the cerebrospinal fluid (CSF).

Indications for CSF examination prior to initiating treatment of syphilis include the following:

  • Evidence of neurosyphilis
  • Evidence of tertiary syphilis (eg, aortitis, gumma, iritis)
  • Treatment failure
  • Patients with HIV infection with late latent syphilis or syphilis of unknown duration
  • Rapid plasma reagin (RPR) test result exceeding 1:32 (unless syphilis duration <1 y)

CSF interpretation is difficult in newborns because the normal values for CSF cell count and protein concentration widely vary. In addition, a negative CSF Venereal Disease Research Laboratory (VDRL) test result cannot exclude neurosyphilis. Conversely, the CSF VDRL test result can be positive in an uninfected newborn with a transplacentally acquired high serum VDRL finding. Thus, all infants suspected of having congenital syphilis should be treated for neurosyphilis.

When distribution shortages of aqueous penicillin G occur, substitution of ampicillin or ceftriaxone may be necessary (see the CDC web page "Alternatives to intravenous penicillin G for specific infections" for the most up-to-date recommendations).
  • Congenital syphilis in newborns: Treat the congenital infection, either proven or presumed, with 10-14 days of aqueous penicillin G or procaine penicillin G. Aqueous crystalline penicillin G is recommended if congenital syphilis is proved or is highly suspected. Base dosage on chronologic, not gestational, age. The recommended dosage is 100,000-150,000 U/kg/d IV every 8-12 hours to complete a 10-day to 14-day course. Procaine penicillin G (50,000 U/kg IM) has been recommended as an alternative to treat congenital syphilis, but adequate CSF concentration may not be consistently achieved. Infection is suspected with the following:
    • Physical or radiographic evidence of active disease
    • Serum quantitative nontreponemal titer at least 4 times greater than the maternal titer
    • Reactive CSF VDRL test result or abnormal CSF cell count and/or protein levels
    • Positive immunoglobulin M (IgM) fluorescent treponemal antibody absorption (FTA-ABS) test findings
    • Positive darkfield microscopy findings or positive findings when staining for treponemes in placenta or umbilical cord
  • Congenital syphilis in older infants and children: Treat diagnosed infants older than 4 weeks with aqueous crystalline penicillin (200,000-300,000 U/kg/d IV divided every 6 h for 10-14 d). 
  • Syphilis in pregnancy
    • Treat all pregnant patients with syphilis with penicillin, regardless of the stage of pregnancy.
    • Administer 3 doses of benzathine penicillin (2.4 million U IM at 1-wk intervals).
    • No proven alternative therapy is available for patients who are allergic to penicillin.
    • Erythromycin treatment for the pregnant patients who are allergic to penicillin is not a reliable treatment for the fetus.
  • Early-acquired syphilis (ie, primary, secondary, latent syphilis of <1 y duration): A single dose of IM benzathine penicillin G in a total dose of 50,000 U/kg (not to exceed 2.4 million U) is the recommended treatment. Exclude neurosyphilis by CSF examination in all pediatric patients.
  • Syphilis (>1 y duration): The recommended treatment is benzathine penicillin G, 50,000 U/kg IM (not to exceed 2.4 million U) weekly for 3 successive weeks.
  • Neurosyphilis: The recommended treatment is aqueous crystalline penicillin G (200,000-300,000 U/kg/d IM [50,000 U/kg every 4-6 h]) for 10-14 days (adult dose, 12-24 million U/d [2-4 million U every 4 h]), followed by a single dose of benzathine penicillin (50,000 U/kg/dose, not to exceed 2.4 million U) in 3 weekly doses.

Consultations

  • Infectious disease specialist: Consultation with an infectious disease specialist is useful in most cases.
  • Neurologist: Consultation with a neurologist is prudent if neurosyphilis is present or suspected.
  • Ophthalmologist: Keratitis and optic atrophy are common; slit lamp examination and follow-up are important.
  • Orthopedist: Skeletal gummas most often involve the legs. Bony involvement in congenital syphilis frequently resolves in the first 6 months, but lesions may be painful until healed.
  • Otolaryngologist: Congenital syphilis is a known cause of progressive sensorineural hearing loss. Therefore, hearing screening is recommended for all pediatric patients with congenital syphilis.10

Medication

T pallidum is extremely sensitive to penicillin. Primary, secondary, and early latent syphilis are treated with a single IM dose of penicillin G benzathine (50,000 U/kg; not to exceed 2.4 million U). Nonpregnant patients who are allergic to penicillin and have no evidence of neurosyphilis can be treated with either doxycycline or tetracycline. Incubating syphilis can also be managed with penicillin. Spectinomycin is ineffective for incubating syphilis. Current recommendations for management of congenital syphilis include administration of IV penicillin G aqueous and IM penicillin G procaine for 10-14 days. Either penicillin regimen is considered adequate to manage congenital syphilis.

The Jarisch-Herxheimer reaction is the major complication of therapy and occurs in 50% of patients with primary syphilis, in 90% of those with secondary syphilis, and in 25% of those with early latent syphilis. First described in patients with syphilis by Jarisch in 1895 and then Herxheimer in 1902, the reaction occurs during the first 24 hours of treatment and consists of the abrupt onset of fever, chills, myalgias, headache, tachycardia, hyperventilation, vasodilation with flushing, and mild hypotension.

Onset begins within 2 hours of treatment initiation; the temperature peaks at about 7 hours, and defervescence takes place within 12-24 hours. The reaction, which is self-limited, is associated with an increase in circulating levels of tumor necrosis factor, interleukin (IL)-6, and IL-8.

Antibiotics

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the clinical setting. Antibiotic selection should be guided by blood-culture sensitivity whenever feasible.


Penicillin G benzathine (Bicillin L-A, Permapen)

An injection (300,000 and 600,000 U/mL) that provides sustained levels for 2-4 wk; interferes with synthesis of cell wall mucopeptides during active multiplication, which results in bactericidal activity.

Adult

Primary, secondary, and early latent syphilis (disease duration <1 y): 2.4 million U IM divided once in 2 injection sites
Late latent syphilis (disease duration >1 y): 2.4 million U divided in 2 injection sites qwk for 3 doses

Pediatric

Disease duration <1 year: 50,000 U/kg IM once; not to exceed 2.4 million U/dose
Disease duration >1 year: 50,000 U/kg IM q wk for 3 doses; not to exceed 2.4 million U/dose

Probenecid can increase effectiveness by decreasing clearance; coadministration with tetracyclines can decrease effectiveness

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

IM administration only, do not administer IV; cardiac arrest and death may occur with large doses; not recommended for congenital syphilis; caution in impaired renal function


Penicillin G procaine (Crysticillin A.S., Wycillin)

An injection (300,000 U/mL, 500,000 U/mL, and 600,000 U/mL) that contains 120 mg procaine per 300,000 U; seldom recommended for congenital syphilis because adequate levels in the CSF may not be achieved.

Adult

Pediatric

Congenital syphilis:
Neonates: 50,000 U/kg/d IM qd for 10-14 d

Increases risk of bleeding when concurrently administered with warfarin; ethacrynic acid, aspirin, indomethacin, and furosemide may compete with penicillin G for renal tubular secretion, increasing penicillin serum concentrations; probenecid increases serum levels

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

IM administration only, do not administer IV; cardiac arrest and death may occur with high doses


Penicillin G (Pfizerpen)

Aqueous penicillin injection (K): 1, 5, 10, and 20 million U (contains 1.7 mEq K and 0.3 mEq Na/1 million U penicillin G)
Injection (Na): 5 million U (contains 2 mEq Na/1 million U penicillin G)
Interferes with synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms.

Adult

Neurosyphilis: 2.4 million U IV q4h for 10-14 d

Pediatric

Congenital syphilis:
Neonates: 50,000 U/kg IV q12h for first 7 d, then 50,000 U/kg IV q8h for a total of 10-14 d
Infants and children 4 wk and older: 200,000-300,000 U/kg/d IV divided q6h for 10-14 d

Probenecid can increase effects of penicillin; coadministration of tetracyclines can decrease effects of penicillin

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in impaired renal function


Tetracycline (Sumycin)

May be an alternative to penicillin in nonpregnant patients who are allergic to penicillin; inhibits bacterial protein synthesis by binding with 30S and, possibly, 50S ribosomal subunits.

Adult

500 mg PO qid for 2 wk

Pediatric

Not recommended

Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; can decrease effects of PO contraceptives, causing breakthrough bleeding and increased risk of pregnancy; tetracyclines can increase hypoprothrombinemic effects of anticoagulants

Documented hypersensitivity; severe hepatic dysfunction

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (final half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines


Doxycycline (Vibramycin)

Another alternative to penicillin for nonpregnant patients who are allergic to penicillin; inhibits protein synthesis and, thus, bacterial growth by binding to 30S and, possibly, 50S ribosomal subunits.

Adult

100 mg PO bid for 2 wk

Pediatric

Not recommended

Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can increase hypoprothrombinemic effects of anticoagulants; tetracyclines can decrease effects of PO contraceptives, causing breakthrough bleeding and increased risk of pregnancy

Documented hypersensitivity; severe hepatic dysfunction

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (final half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines


Erythromycin (E.E.S., E-Mycin, Ery-Tab)

An alternative to penicillin for patients who are allergic to penicillin; inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes causing RNA-dependent protein synthesis to arrest.

Adult

500 mg PO qid for 2 wk

Pediatric

Not recommended

Coadministration may increase toxicity of theophylline, digoxin, carbamazepine, and cyclosporine; may potentiate anticoagulant effects of warfarin; coadministration with lovastatin and simvastatin, increases risk of rhabdomyolysis

Documented hypersensitivity; hepatic impairment

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Does not effectively treat fetal infection; caution in liver disease; GI adverse effects are common (administer give doses pc); discontinue use if nausea, vomiting, malaise, abdominal colic, or fever occur

More on Syphilis

Overview: Syphilis
Differential Diagnoses & Workup: Syphilis
Treatment & Medication: Syphilis
Follow-up: Syphilis
Multimedia: Syphilis
References
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Further Reading

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Keywords

syphilis, bejel, English pox, French disease, French pox, great pox, Italian disease, lues, sexually transmitted disease, STD, Treponema pallidum, venereal disease, venereal pox, , venereal syphilis, yaws, endemic syphilis, pinta, neurosyphilis, meningeal syphilis, human immunodeficiency virus, HIV, chancre, meningitis, inflammatory ocular hypertension syndrome, condyloma lata, aortitis, aortic aneurysm, coronary stenosis, treatment, diagnosis

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Contributor Information and Disclosures

Author

Muhammad Waseem, MD, Associate Professor of Emergency Medicine in Clinical Pediatrics, Weill Medical College of Cornell University; Consulting Staff, Department of Pediatrics, Bronx Lebanon Hospital; Consulting Staff, Department of Emergency Medicine, Lincoln Medical and Mental Health Center
Muhammad Waseem, MD is a member of the following medical societies: American Academy of Pediatrics and American Medical Association
Disclosure: Nothing to disclose.

Coauthor(s)

Muhammad Aslam, MD, Instructor in Pediatrics, Harvard Medical School; Staff Physician, Department of Medicine/ Division of Newborn Medicine, Children's Hospital Boston
Muhammad Aslam, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Medical Association, Massachusetts Medical Society, and Southern Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Robert W Tolan Jr, MD, Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine
Robert W Tolan Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa, and Physicians for Social Responsibility
Disclosure: GlaxoSmithKline Honoraria Speaking and teaching; MedImmune Honoraria Speaking and teaching; Merck Honoraria Speaking and teaching; sanofi pasteur Honoraria Speaking and teaching; Baxter Healthcare Honoraria Speaking and teaching

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Leslie L Barton, MD, Professor, Program Director, Department of Pediatrics, University of Arizona School of Medicine
Leslie L Barton, MD is a member of the following medical societies: American Academy of Pediatrics, Association of Pediatric Program Directors, Infectious Diseases Society of America, and Pediatric Infectious Diseases Society
Disclosure: Nothing to disclose.

CME Editor

Daniel Rauch, MD, FAAP, Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine
Daniel Rauch, MD, FAAP is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, and Society of Hospital Medicine
Disclosure: Baxter Honoraria Consulting

Chief Editor

Russell W Steele, MD, Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine
Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association
Disclosure: None None None

 
 
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