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Syphilis: Treatment & Medication
Updated: Jul 17, 2009
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Treatment
Emergency Department Care
Penicillin was established as an effective treatment before the widespread use of randomized clinical trials. The treatment guidelines published by the Centers for Disease Control and Prevention (CDC) are based largely on uncontrolled trials and expert opinion. Guidelines are based on staging, with later stages requiring longer courses of treatment due to the slower rate of bacterial replication.
- Primary or secondary syphilis - Benzathine penicillin G 2.4 million units IM in a single dose
- Early latent syphilis - Benzathine penicillin G 2.4 million units IM in a single dose
- Late latent syphilis or latent syphilis of unknown duration - Benzathine penicillin G 7.2 million units total, administered as 3 doses of 2.4 million units IM each at 1-week intervals
- Penicillin allergy - Skin testing is recommended for patients with a history of penicillin allergy. Patients who are skin test negative can receive conventional treatment with penicillin. Skin test positive patients should be desensitized in the hospital.
- Pregnancy - Treatment appropriate to the stage of syphilis is recommended.6
Consultations
If the ED physician has concerns or questions about the patient's presentation or course, an infectious disease consultation is a reasonable course of action.Additionally, the CDC, World Health Organization (WHO), and Morbidity and Mortality Weekly Report (MMWR) are an excellent updated references. Syphilis may be reportable to public health authorities in some jurisdictions.
Medication
The goal of pharmacotherapy is to eradicate the causative organism of syphilis, T pallidum. The drug of choice is parenteral penicillin G for all stages of syphilis. Since the dividing time of T pallidum is slow (days), penicillin G benzathine is the only penicillin effective for single-dose therapy because it is in depo form and levels remain therapeutic in the blood for up to 30 days. Avoiding Bicillin C-R (combination procaine and benzathine), which remains in blood for only 7 days, is essential.
Since T pallidum resistance to penicillin has not emerged, the primary need for alternative drugs in treating syphilis is reserved for penicillin-allergic patients. Erythromycin has been associated with high failure rates. Doxycycline may be an option for patients who refuse parenteral therapy. A meta-analysis of randomized clinical trials comparing azithromycin to benzathine penicillin G for early syphilis was published in 2008 showing favorable results for azithromycin.8
As the treponemes die after initiation of treatment, they release inflammatory molecules that trigger a cytokine cascade possibly leading to the Jarisch-Herxheimer reaction. Symptoms include myalgias, fever, headache, and tachycardia, sometimes with exacerbation whatever current symptoms are manifested such as the rash or the chancre. The reaction is usually limited to 24 hours after onset. Antipyretics and analgesics are useful to control symptoms. Patients should be informed of the possibility of this reaction prior to treatment.
Antibiotics
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.
Azithromycin (Zithromax)
Acts by binding to 50S ribosomal subunit of susceptible microorganisms and blocks dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Nucleic acid synthesis is not affected.
Concentrates in phagocytes and fibroblasts as demonstrated by in vitro incubation techniques. In vivo studies suggest that concentration in phagocytes may contribute to drug distribution to inflamed tissues. Treats mild-to-moderate microbial infections.
Adult
Day 1: 500 mg PO
Days 2-5: 250 mg PO qd
Alternatively, 1 g PO once
Pediatric
<6 months: Not established
>6 months:
Day 1: 10 mg/kg PO once; not to exceed 500 mg/d
Days 2-5: 5 mg/kg PO qd; not to exceed 250 mg/d
May increase toxicity of theophylline, warfarin, and digoxin; effects are reduced with coadministration of aluminum and/or magnesium antacids; nephrotoxicity and neurotoxicity may occur when coadministered with cyclosporine
Documented hypersensitivity; hepatic impairment; do not administer with pimozide
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Site reactions can occur with IV route; bacterial or fungal overgrowth may result from prolonged antibiotic use; may increase hepatic enzymes and cholestatic jaundice; caution in patients with impaired hepatic function or prolonged QT intervals
Doxycycline (Bio-Tab, Doryx, Doxy, Periostat, Vibramycin, Vibra-Tabs)
Broad-spectrum, synthetically derived bacteriostatic antibiotic in the tetracycline class. Almost completely absorbed, concentrates in bile, and is excreted in urine and feces as a biologically active metabolite in high concentrations.
Inhibits protein synthesis and, thus, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. May block dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest.
Adult
200 mg PO/IV immediately and 100 mg hs, followed by 100 mg bid for 3 d
Alternatively, 100-200 mg PO bid for 14 d
Pediatric
<8 years: Not recommended
>8 years: 2-5 mg/kg/d PO/IV in 1-2 divided doses; not to exceed 200 mg/d
Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can increase hypoprothrombinemic effects of anticoagulants; tetracyclines can decrease effects of oral 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 (last one half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconi-like syndrome may occur with outdated tetracyclines
Penicillin G benzathine (Bicillin)
Interferes with synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms.
Adult
Disease <1 year: 2.4 million U IM once in 2 injection sites
Disease >1 year: 2.4 million U in 2 injection sites weekly for 3 doses
Pediatric
Disease <1 year: 50,000 U/kg IM once; not to exceed 2.4 million U/dose
Disease >1 year: 50,000 U/kg IM weekly for 3 doses; not to exceed 2.4 million U/dose
Probenecid can increase effectiveness by decreasing clearance; tetracyclines can decrease effectiveness
Documented hypersensitivity
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
More on Syphilis |
| Overview: Syphilis |
| Differential Diagnoses & Workup: Syphilis |
 Treatment & Medication: Syphilis |
| Follow-up: Syphilis |
| Multimedia: Syphilis |
| References |
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References
Primary and secondary syphilis--United States, 2003-2004. MMWR Morb Mortal Wkly Rep. Mar 17 2006;55(10):269-73. [Medline].
Harrison LW. The Oslo study of untreated syphilis, review and commentary. Br J Vener Dis. Jun 1956;32(2):70-8. [Medline].
Rockwell DH, Yobs AR, Moore MB Jr. The Tuskegee Study of Untreated Syphilis; the 30th year of Observation. Arch Intern Med. Dec 1964;114:792-8. [Medline].
Sexually Transmitted Disease Surveillance, 2007. Atlanta, Georgia: Centers for Disease Control and Prevention; 2008. 33. [Full Text].
[Guideline] Screening for syphilis infection in pregnancy: U.S. Preventive services task force reaffirmation recommendation statement. Ann Intern Med. May 19 2009;150(10):705-9. [Medline]. [Full Text].
[Guideline] Workowski KA, Berman SM. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep. Aug 4 2006;55:1-94. [Medline]. [Full Text].
[Guideline] U.S. Preventive Services Task Force. Screening for Syphilis Infection. Recommendation Statement. 2004. [Full Text].
Bai ZG, Yang KH, Liu YL, et al. Azithromycin vs. benzathine penicillin G for early syphilis: a meta-analysis of randomized clinical trials. Int J STD AIDS. Apr 2008;19(4):217-21. [Medline].
[Guideline] Calonge N. Screening for syphilis infection: recommendation statement. Ann Fam Med. Jul-Aug 2004;2(4):362-5. [Medline]. [Full Text].
Centers for Disease Control and Prevention. Primary and Secondary Syphilis -- United States, 2003-2004. MMWR Morb Mortal Wkly Rep. March 17, 2006;55(10):269-273. [Full Text].
Csonka GW, Oates JK. Sexually Transmitted Diseases. WB Saunders; 1990:227-76.
Department of Health and Human Services. Sexually Transmitted Diseases Surveillance 2004 Report. Syphilius Surveillance Report. 2005;[Full Text].
Hoeprich PD, Jordan MC. Infectious Diseases. 4th ed. Lippincott-Raven; 1989:666-83.
Isselbacher KJ, Braunwald E, Wilson JD. Harrison's Principles of Internal Medicine. 13th ed. McGraw-Hill: 1994:726-37.
Kent ME, Romanelli F. Reexamining syphilis: an update on epidemiology, clinical manifestations, and management. Ann Pharmacother. Feb 2008;42(2):226-36. [Medline].
Rosahn PD. Autopsy studies in syphilis; a monograph. Washington: U.S. Dept. of Health, Education, and Welfare, Public Health Service, Bureau of State Services, Communicable Disease Center, Venereal Disease Branch; 1948. U.S. Public Health Service Publication.
Further Reading
Keywords
syphilis, syphilis treatment, syphilis symptoms, syphilis symptoms, STDs, sexually transmitted diseases, Treponema pallidum, T pallidum, primary syphilis, secondary syphilis, early latent syphilis, late latent syphilis, tertiary syphilis, gummatous syphilis, cardiovascular syphilis, neurosyphilis, advanced syphilis, chancre, genital chancre, inguinal adenitis, condylomata lata, the great impostor
