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Syphilis Medication

  • Author: Pranatharthi Haran Chandrasekar, MBBS, MD; Chief Editor: Michael Stuart Bronze, MD  more...
 
Updated: Feb 16, 2016
 

Medication Summary

The goal of pharmacotherapy is to eradicate the causative organism of syphilis, T pallidum. Penicillin is the mainstay of treatment, the standard by which other modes of therapy are judged, and the only therapy recommended for neurosyphilis, congenital syphilis, or syphilis during pregnancy.

Penicillin

The drug of choice is parenteral penicillin G for all stages of syphilis. According to the 2010 CDC STD treatment guidelines, penicillin G is the only therapy that is clinically documented to be effective against syphilis during pregnancy.[26] 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.

On rare occasions, T pallidum has been found to persist after adequate penicillin therapy; however, no indication exists that T pallidum has acquired resistance to the drug.

According to the Centers for Disease Control and Prevention (CDC; see current CDC recommendations), patients with known penicillin allergies should undergo penicillin allergy skin testing and penicillin desensitization, if necessary.[40]

Alternatives to penicillin

Since T pallidum resistance to penicillin has not emerged, the primary need for alternative drugs in treating syphilis is reserved for penicillin-allergic patients.

Researchers are studying the efficacy of ceftriaxone and azithromycin in treating syphilis. Central nervous system (CNS) penetration and its similarity to penicillin support the use of ceftriaxone in the treatment of syphilis. Studies are presently inconclusive, and CDC guidelines neither support nor refute its use. Given the limited data available to support its efficacy, prudence dictates a 5- to 7-day course of treatment for early syphilis.

The long half-life of azithromycin and its clinical efficacy in vitro against syphilis support its use in treating early syphilis. At present, however, clinical data remain insufficient to recommend its use, and widespread resistance limits the use in many areas (especially in the Pacific Northwest).

Doxycycline may be an option for patients who refuse parenteral therapy or who have penicillin allergy.

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Antibiotics

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Penicillin G benzathine (Bicillin L-A)

 

Benzathine penicillin G is the first-line agent for primary and secondary syphilis infection. It is a spirocheticide with in vivo activity against T pallidum. It interferes with cell wall mucopeptide synthesis during replication.

Penicillin G procaine

 

Penicillin G procaine is the first-line agent for treating late latent syphilis.

Doxycycline (Doryx, Vibramycin)

 

Doxycycline is used as alternative therapy for syphilis infection. It inhibits bacterial growth by binding to the 30S ribosomal unit, preventing protein synthesis.

Tetracycline (Sumycin)

 

Tetracycline is used as alternative therapy for syphilis infection. It inhibits bacterial growth by binding to the 30S ribosomal unit, preventing protein synthesis.

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

 

Erythromycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. In children, age, weight, and severity of infection determine proper dosage. When twice-daily dosing is desired, half of the total daily dose may be taken q12h. For more severe infections, double the dose.

Ceftriaxone (Rocephin)

 

Ceftriaxone is an alternative agent for penicillin-allergic patients, with limited data to support its use. It is a third-generation cephalosporin. It arrests bacterial growth by binding to one or more penicillin binding proteins.

Azithromycin (Zithromax)

 

Azithromycin acts by binding to the 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.

Azithromycin 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. This drug is used to treat mild-to-moderate microbial infections.

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Uricosuric agents

Class Summary

Uricosuric agents are used to increase serum concentration of certain antibiotics and other drugs.

Probenecid

 

Probenecid inhibits tubular secretion of penicillin and usually increases penicillin plasma levels by any route the antibiotic is administered. A 2- to 4-fold elevation has been demonstrated for various penicillins. Probenecid is used as an adjunct to penicillin in late latent and neurosyphilis.

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Contributor Information and Disclosures
Author

Pranatharthi Haran Chandrasekar, MBBS, MD Professor, Chief of Infectious Disease, Program Director of Infectious Disease Fellowship, Department of Internal Medicine, Wayne State University School of Medicine

Pranatharthi Haran Chandrasekar, MBBS, MD is a member of the following medical societies: American College of Physicians, American Society for Microbiology, International Immunocompromised Host Society, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Coauthor(s)

 

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

John L Brusch, MD, FACP Assistant Professor of Medicine, Harvard Medical School; Consulting Staff, Department of Medicine and Infectious Disease Service, Cambridge Health Alliance

John L Brusch, MD, FACP is a member of the following medical societies: American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Chief Editor

Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, Oklahoma State Medical Association, Southern Society for Clinical Investigation, Association of Professors of Medicine, American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Additional Contributors

Daniel J Hogan, MD Clinical Professor of Internal Medicine (Dermatology), Nova Southeastern University College of Osteopathic Medicine; Investigator, Hill Top Research, Florida Research Center

Daniel J Hogan, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Contact Dermatitis Society, Canadian Dermatology Association

Disclosure: Nothing to disclose.

Daniel R Lucey, MD, MPH, MD, MPH 

Daniel R Lucey, MD, MPH, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians

Disclosure: Nothing to disclose.

Eric L Weiss, MD, DTM&H Medical Director, Office of Service Continuity and Disaster Planning, Fellowship Director, Stanford University Medical Center Disaster Medicine Fellowship, Chairman, SUMC and LPCH Bioterrorism and Emergency Preparedness Task Force, Clinical Associate Professor, Department of Surgery (Emergency Medicine), Stanford University Medical Center

Eric L Weiss, MD, DTM&H is a member of the following medical societies: American College of Emergency Physicians, American College of Occupational and Environmental Medicine, American Medical Association, American Society of Tropical Medicine and Hygiene, Physicians for Social Responsibility, Southeastern Surgical Congress, Southern Oncology Association of Practices, Southern Clinical Neurological Society, Wilderness Medical Society

Disclosure: Nothing to disclose.

Joseph J Sachter, MD, FACEP Consulting Staff, Department of Emergency Medicine, Muhlenberg Regional Medical Center

Joseph J Sachter, MD, FACEP is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Association for Physician Leadership, American Medical Association, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Timothy McCalmont, MD Director, UCSF Dermatopathology Service, Professor of Clinical Pathology and Dermatology, Departments of Pathology and Dermatology, University of California at San Francisco; Editor-in-Chief, Journal of Cutaneous Pathology

Timothy McCalmont, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, American Society of Dermatopathology, California Medical Association, College of American Pathologists, United States and Canadian Academy of Pathology

Disclosure: Received consulting fee from Apsara for independent contractor.

Richard H Sinert, DO Professor of Emergency Medicine, Clinical Assistant Professor of Medicine, Research Director, State University of New York College of Medicine; Consulting Staff, Vice-Chair in Charge of Research, Department of Emergency Medicine, Kings County Hospital Center

Richard H Sinert, DO is a member of the following medical societies: American College of Physicians, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Paul Krusinski, MD Director of Dermatology, Fletcher Allen Health Care; Professor, Department of Internal Medicine, University of Vermont College of Medicine

Paul Krusinski, MD is a member of the following medical societies: American Academy of Dermatology, American College of Physicians, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Texas Medical Association, Association of Military Dermatologists, Texas Dermatological Society

Disclosure: Nothing to disclose.

Brian Euerle, MD, FACEP Associate Professor, Department of Emergency Medicine, Director of Emergency Ultrasound Program, University of Maryland School of Medicine

Brian Euerle, MD, FACEP is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Maria M Diaz, MD Staff Physician, Department of Emergency Medicine, Parkland Medical Center

Maria M Diaz, MD is a member of the following medical societies: American College of Emergency Physicians, Phi Beta Kappa, Emergency Medicine Residents' Association

Disclosure: Nothing to disclose.

References
  1. Cox DL, Chang P, McDowall AW, Radolf JD. The outer membrane, not a coat of host proteins, limits antigenicity of virulent Treponema pallidum. Infect Immun. 1992 Mar. 60(3):1076-83. [Medline]. [Full Text].

  2. Fitzgerald TJ. The Th1/Th2-like switch in syphilitic infection: is it detrimental?. Infect Immun. 1992 Sep. 60(9):3475-9. [Medline]. [Full Text].

  3. Bowen V, Su J, Torrone E, Kidd S, Weinstock H. Increase in Incidence of Congenital Syphilis - United States, 2012-2014. MMWR Morb Mortal Wkly Rep. 2015 Nov 13. 64:1241-5. [Medline].

  4. Patton ME, Su JR, Nelson R, Weinstock H, Centers for Disease Control and Prevention (CDC). Primary and secondary syphilis--United States, 2005-2013. MMWR Morb Mortal Wkly Rep. 2014 May 9. 63 (18):402-6. [Medline].

  5. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2007 Supplement, Syphilis Surveillance Report. Centers for Disease Control and Prevention. Centers for Disease Control and Prevention. Available at http://www.cdc.gov/std/Syphilis2007/. Accessed: April 14.

  6. CDC. Primary and secondary syphilis--United States, 2003-2004. MMWR Morb Mortal Wkly Rep. 2006 Mar 17. 55(10):269-73. [Medline].

  7. World Health Organization. Global prevalence and incidence of selected curable sexually transmitted infections: Overview and estimates. Geneva: 2001. [Full Text].

  8. Akovbian VA, Gomberg MA, Prokhorenkov VI. Syphilitic vignettes from Russia. Dermatol Clin. 1998 Oct. 16(4):687-90, x. [Medline].

  9. HIV prevention through early detection and treatment of other sexually transmitted diseases--United States. Recommendations of the Advisory Committee for HIV and STD prevention. MMWR Recomm Rep. 1998 Jul 31. RR-12:1-24. [Medline]. [Full Text].

  10. Cooley LA1, Pearl ML, Flynn C, Ross C, Hart-Cooper G, Elmore K, et al. Low viral suppression and high HIV diagnosis rate among men who have sex with men with syphilis--Baltimore, Maryland. Sex Transm Dis. 2015 Apr. 42(4):226-31. [Medline].

  11. Su JR, Weinstock H. Epidemiology of co-infection with HIV and syphilis in 34 states, United States—2009. Proceedings of the 2011 National HIV Prevention Conference, August 13-17, 2011.

  12. HARRISON LW. The Oslo study of untreated syphilis, review and commentary. Br J Vener Dis. 1956 Jun. 32(2):70-8. [Medline]. [Full Text].

  13. ROCKWELL DH, YOBS AR, MOORE MB Jr. THE TUSKEGEE STUDY OF UNTREATED SYPHILIS; THE 30TH YEAR OF OBSERVATION. Arch Intern Med. 1964 Dec. 114:792-8. [Medline].

  14. McClure EM, Goldenberg RL. Infection and stillbirth. Semin Fetal Neonatal Med. 2009 Aug. 14(4):182-9. [Medline].

  15. Kupka R, Kassaye T, Saathoff E, Hertzmark E, Msamanga GI, Fawzi WW. Predictors of stillbirth among HIV-infected Tanzanian women. Acta Obstet Gynecol Scand. 2009. 88(5):584-92. [Medline]. [Full Text].

  16. Dismukes WE, Delgado DG, Mallernee SV, Myers TC. Destructive bone disease in early syphilis. JAMA. 1976 Dec 6. 236(23):2646-8. [Medline].

  17. Sule RR, Deshpande SG, Dharmadhikari NJ, Joshi VR. Late cutaneous syphilis. Cutis. 1997 Mar. 59(3):135-7. [Medline].

  18. [Guideline] U.S. Preventive Services Task Force. Screening for Syphilis Infection. Recommendation Statement. 2004. [Full Text].

  19. Workowski KA, Bolan GA. Centers for Disease Control and Prevention Sexually Transmitted Diseases Treatment Guidelines. MMWR. June 5, 2015. 64(RR3):1-137. [Full Text].

  20. Schmid GP. Serologic screening for syphilis. Rationale, cost, and realpolitik. Sex Transm Dis. 1996 Jan-Feb. 23(1):45-50. [Medline].

  21. Young H. Syphilis. Serology. Dermatol Clin. 1998 Oct. 16(4):691-8. [Medline].

  22. 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):148-50. [Medline].

  23. [Guideline] Workowski KA, Berman SM. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep. 2006 Aug 4. 55:1-94. [Medline].

  24. U.S. Preventive Services Task Force. Screening for syphilis infection in pregnancy: U.S. Preventive Services Task Force reaffirmation recommendation statement. Ann Intern Med. 2009 May 19. 150(10):705-9. [Medline]. [Full Text].

  25. Ghanem KG. Management of Adult Syphilis: Key Questions to Inform the 2015 Centers for Disease Control and Prevention Sexually Transmitted Diseases Treatment Guidelines. Clin Infect Dis. 2015 Dec 15. 61 Suppl 8:S818-36. [Medline].

  26. [Guideline] Workowski KA, Berman S. Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep. 2010 Dec 17. 59:1-110. [Medline]. [Full Text].

  27. Ghanem KG, Workowski KA. Management of adult syphilis. Clin Infect Dis. 2011 Dec. 53 Suppl 3:S110-28. [Medline].

  28. Fiumara NJ. Treatment of primary and secondary syphilis. Serological response. JAMA. 1980 Jun 27. 243(24):2500-2. [Medline].

  29. Collart P, Poitevin M, Milovanovic A, Herlin A, Durel J. Kinetic study of serum penicillin concentrations after single doses of benzathine and benethamine penicillins in young and old people. Br J Vener Dis. 1980 Dec. 56 (6):355-62. [Medline].

  30. Hagdrup HK, Lange Wantzin G, Secher L, Rosdahl VT. Penicillin concentrations in serum following weekly injections of benzathine penicillin G. Chemotherapy. 1986. 32 (2):99-101. [Medline].

  31. Frentz G, Nielsen PB, Espersen F, Czartoryski A, Aastrup H. Penicillin concentrations in blood and spinal fluid after a single intramuscular injection of penicillin G benzathine. Eur J Clin Microbiol. 1984 Apr. 3 (2):147-9. [Medline].

  32. Nathan L, Bawdon RE, Sidawi JE, Stettler RW, McIntire DM, Wendel GD Jr. Penicillin levels following the administration of benzathine penicillin G in pregnancy. Obstet Gynecol. 1993 Sep. 82 (3):338-42. [Medline].

  33. Augenbraun M, Workowski K. Ceftriaxone therapy for syphilis: report from the emerging infections network. Clin Infect Dis. 1999 Nov. 29(5):1337-8. [Medline].

  34. Bai ZG, Yang KH, Liu YL, Tian JH, Ma B, Mi DH, et al. Azithromycin vs. benzathine penicillin G for early syphilis: a meta-analysis of randomized clinical trials. Int J STD AIDS. 2008 Apr. 19(4):217-21. [Medline].

  35. Hook EW 3rd, Behets F, Van Damme K, Ravelomanana N, Leone P, Sena AC, et al. A phase III equivalence trial of azithromycin versus benzathine penicillin for treatment of early syphilis. J Infect Dis. 2010 Jun 1. 201(11):1729-35. [Medline].

  36. Grimes M, Sahi SK, Godornes BC, Tantalo LC, Roberts N, Bostick D, et al. Two mutations associated with macrolide resistance in Treponema pallidum: increasing prevalence and correlation with molecular strain type in Seattle, Washington. Sex Transm Dis. 2012 Dec. 39 (12):954-8. [Medline].

  37. Golden MR, Wasserheit JN. Prevention of viral sexually transmitted infections--foreskin at the forefront. N Engl J Med. 2009 Mar 26. 360(13):1349-51. [Medline].

  38. Tobian AA, Serwadda D, Quinn TC, Kigozi G, Gravitt PE, Laeyendecker O, et al. Male circumcision for the prevention of HSV-2 and HPV infections and syphilis. N Engl J Med. 2009 Mar 26. 360(13):1298-309. [Medline]. [Full Text].

  39. Augenbraun MH, Rolfs R. Treatment of syphilis, 1998: nonpregnant adults. Clin Infect Dis. 1999 Jan. 28 Suppl 1:S21-8. [Medline].

  40. CDC. Penicillin Allergy-STD Treatment Guidelines 2015. Department of Health and Human Services. Available at http://www.cdc.gov/std/tg2015/pen-allergy.htm.

  41. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance, 2007. 2008. 33. Atlanta, Georgia:[Full Text].

  42. CDC. Trends - STD Surveillance 2006. Department of Health and Human Services. Available at http://www.cdc.gov/std/stats/trends2006.htm#syphilistrends.

  43. CDC. Summary of notifiable diseases, United States, 1997. MMWR Morb Mortal Wkly Rep. 1998 Nov 20. 46(54):ii-vii, 3-87. [Medline].

  44. Nakashima AK, Rolfs RT, Flock ML, Kilmarx P, Greenspan JR. Epidemiology of syphilis in the United States, 1941--1993. Sex Transm Dis. 1996 Jan-Feb. 23(1):16-23. [Medline].

  45. Centers for Disease Control and Prevention. STD Surveillance 2003, Atlanta, Ga. 2004. Centers for Disease Control and Prevention:

  46. Centers for Disease Control and Prevention (CDC). Azithromycin treatment failures in syphilis infections--San Francisco, California, 2002-2003. MMWR Morb Mortal Wkly Rep. 2004 Mar 12. 53(9):197-8. [Medline].

 
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Syphilis. These photographs depict the characteristic chancre observed in primary syphilis. Used with permission from Wisdom (Left) A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989. (Right) Centers for Disease Control and Prevention
Syphilis. These photographs show the disseminated rash observed in secondary syphilis. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.
Syphilis. These photographs show close-up images of gummas observed in tertiary syphilis. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.
Syphilis. This photograph depicts primary syphilis "kissing" lesions. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.
Syphilis. Palmar lesions observed in secondary syphilis. Used with permission from Wisdom (Left) A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989. (Right) Centers for Disease Control and Prevention
These photographs illustrate examples of condylomata lata. The lesions resemble genital warts (condylomata acuminata). Fluids exuding from these lesions are highly infectious. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.
Syphilis. These photographs illustrate typical facies of congenital syphilis. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.
Syphilis. This photograph shows an example of Hutchinson teeth in congenital syphilis. Note notching. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.
Syphilis. This photograph illustrates chorioretinitis of congenital syphilis. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.
Syphilitic chancre
Secondary syphilis - Exanthem
Secondary syphilis - Exanthem
Lues hematoxylin and eosin stain. Histopathological examination shows a lichenoid infiltrate that is stereotypical of the secondary stage of syphilis. Note that vacuolar alteration of the superjacent epithelium can be seen much like a noninfectious form of lichenoid dermatitis. The subjunctional infiltrate is rich in histiocytes and plasmacytes. At times, an overtly granulomatous lichenoid infiltrate can be seen.
Lues TP stain. Immunoperoxidase staining for T pallidum highlights many slender coiled organisms residing in the perijunctional zone. Occasionally, organisms can also be found in the upper dermis or around adnexal structures.
 
 
 
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