Current standards for syphilis treatment: comparing the russian and foreign guidelines (part II)

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The introduction of penicillin has been a breakthrough in the treatment of syphilis. For 70 years, penicillin remains the preferred drug for the treatment of all forms of the disease; its effectiveness has been proven by wide experience gained from clinical observations. However, a very limited number of published meta-analyzes, systematic reviews and data from randomized controlled trials on the comparative assessment of the effectiveness of various antibiotics and treatment regimens are currently available. Some aspects of syphilis treatment are insufficiently developed, particularly, the treatment schedules for neurosyphilis, syphilis in pregnancy, syphilis in HIV-infected individuals and persons allergic to penicillin. There are disagreements in the assessment of the clinical significance of serofast state after a course of antibiotic therapy. There is no uniform approach to the management of patients with treatment failures. This article compares the Russian standards for syphilis treatment set out in the «Federal guidelines for the management of patients with syphilis» with the current European recommendations of the International Union against Sexually Transmitted Infections (IUSTI) and the recommendations of the US Centers for Disease Control and Prevention (CDC). The peculiarities of these guidelines, their strengths and shortcomings, as well as controversial issues of syphilis therapy are discussed. The differences between the domestic and foreign recommendations are more significant in the section concerning the treatment of syphilis than in the section of diagnosis.

About the authors

T. V. Krasnoselskikh

First Pavlov State Medical University

Author for correspondence.
Russian Federation

E. V. Sokolovskiy

First Pavlov State Medical University

Russian Federation


  1. Janier M., Hegyi V., Dupin N. et al. 2014 European guideline on the management of syphilis. J Eur Acad Dermatol Venereol 2014; 28 (12): 1581-1593.
  2. Lafond R.E., Lukehart S.A. Biological basis for syphilis. Clin Microbiol Rev 2006; 19 (1): 29-49.
  3. Draft for Public Comment Version: Sexually Transmitted Diseases Treatment Guidelines, 2014. Centers for Disease Control and Prevention [Official website]. Access mode:
  4. Лосева О.К. Современные проблемы лечения сифилитической инфекции. Эффективная фармакотерапия 2011; (10): 42-45
  5. Clement M.E., Okeke N.L., Hicks C.B. Treatment of syphilis: a systematic review. JAMA 2014; 312 (18); 1905-1917.
  6. Dowell D., Polgreen P.M., Beekmann S.E. et al. Dilemmas in the management of syphilis: a survey of infectious diseases experts. Clin Infect Dis 2009; 49 (10): 1526-1529.
  7. Федеральные клинические рекомендации по ведению больных сифилисом. М, 2013. 40
  8. Idsoe O., Guthe T., Willcox R.R. Penicillin in the treatment of syphilis. The experience of three decades. Bull WHO 1972; 47: 1-68.
  9. Dunlop E.M. Survival of treponemes after treatment, comments, clinical conclusions and recommendations. Genitourin Med 1985; 61 (5): 293-301.
  10. Rolfs R.T., Joesoef M.R., Hendershot E.F. et al. A randomized trial of enhanced therapy for early syphilis in patients with and without human immunodeficiency virus infection. The Syphilis and HIV Study Group. N Engl J Med 1997; 337 (5): 307-314.
  11. Manavi K., McMillan A. The outcome of treatment of early latent syphilis and syphilis with undetermined duration in HIV-infected and HIV-uninfected patients. Int J STD AIDS 2007; 18 (12); 814-818.
  12. Jinno S., Anker B., Kaur P. et al. Predictors of serological failure after treatment in HIV-infected patients with early syphilis in the emerging era of universal antiretroviral therapy use. BMC Infect Dis 2013; 13; 605.
  13. Yang C.J., Lee N.Y., Chen T.C. et al. One dose versus three weekly doses of benzathine penicillin G for patients co-infected with HIV and early syphilis: a multicenter, prospective observational study. PLoS One 2014; 9 (10): e109667.
  14. Ghanem K.G., Workowski K.A. Management of adult syphilis. Clin Infect Dis, 2011; 53 Suppl 3: S110-S128.
  15. Dionne-Odom J., Karita E., Kilembe W. et al. Syphilis treatment response among HIV-discordant couples in Zambia and Rwanda. Clin Infect Dis 2013; 56 (12): 1829-1837.
  16. Sena A.C., Wolff M., Martin D.H. et al: Predictors of serological cure and serofast state after treatment in HIV-negative persons with early syphilis. Clin Infect Dis 2011; 53 (11): 1092- 1099.
  17. Myint M., Bashiri H., Harrington R.D., Marra C.M. Relapse of secondary syphilis after benzathine penicillin G: molecular analysis. Sex Transm Dis 2004; 31 (3): 196-199.
  18. Walter T., Lebouche B., Miailhes P. et al. Symptomatic relapse of neurologic syphilis after benzathine penicillin G therapy for primary or secondary syphilis in HIV-infected patients. Clin Infect Dis 2006; 43 (6): 787-790.
  19. Ghanem K.G., Erbelding E.J., Wiener Z.S., Rompalo A.M. Serological response to syphilis treatment in HIV-positive and HIV-negative patients attending sexually transmitted diseases clinics. Sex Transm Infect 2007; 83 (2): 97-101.
  20. Blank L.J., Rompalo A.M., Erbelding E.J. et al. Treatment of syphilis in HIV-infected subjects: a systematic review of the literature. Sex Transm Infect 2011; 87 (1): 9-16.
  21. Sena A.C., Wolff M., Behets F. et al. Response to therapy following retreatment of serofast early syphilis patients with benzathine penicillin. Clin Infect Dis 2013; 56 (3): 420-422.
  22. Dunlop E.M. Persistence of treponemes after treatment. Br Med J 1972; 2 (5813): 577-580.
  23. Yogeswari L., Chacko C.W. Persistence of T. pallidum and its significance in penicillin-treated seropositive late syphilis. Br J Vener Dis 1971; 47 (5): 339-347.
  24. Woznicová V., Heroldová M. Detection of Treponema pallidum DNA in the serum of an adequately treated patient with latent syphilis. Acta Derm Venereol 2007; 87 (4): 379-380.
  25. Goh B.T., Smith G.W., Samarasinghe L. et al. Penicillin concentrations in serum and cerebrospinal fluid after intramuscular injection of aqueous procaine penicillin 0,6 MU with and without probenecid. Br J Vener Dis 1984; 60 (6): 371-373.
  26. Crowe G., Theodore C., Forster G.E., Goh B.T. Acceptability and compliance with daily injections of procaine penicillin in the treatment of syphilis - treponemal infection. Sex Transm Dis 1997; 24 (3): 127-130.
  27. Smith N.H., Musher D.M., Huang D.B. et al. Response of HIV-infected patients with asymptomatic syphilis to intensive intramuscular therapy with ceftriaxone or procaine penicillin. Int J STD AIDS 2004; 15 (5); 328-332.
  28. Дмитриев Г.А., Борисенко К.К., Беднова В.Н. и др. Фармакокинетическое обоснование применения бициллина-1 при лечении больных ранними формами сифилиса. ЗППП 1997; (2): 16-17
  29. Аковбян В.А., Фёдорова Л.Д. Размышления о бензатин бензилпенициллине. 3ППП 1996; (3): 33-38
  30. Чеботарев В.В., Батурин В.А. Сифилис: современный алгоритм лечения больных и диспансеризации, основанный на фармакокинетике пенициллинов. Ставрополь, Изд-во Ставроп. гос. мед. акад. 2010; 178
  31. Чеботарева Н.В. Современная антибиотико-терапия сифилиса пенициллинами на основании фармакокинетических исследований: Автореф. дис. ... д-ра мед. наук. М, 2007; 38
  32. Чеботарев В.В., Чеботарева Н.В. Последствия эпидемии сифилиса в России и пути ее решения. Совр. пробл. дерматовенерол. иммунол. врач. косметол. 2010; (5): 5-9
  33. Лосева О.К., Китаева Н.В., Тоскин И.А. Результаты клинико-серологического наблюдения после лечения больных ранними формами сифилиса с разной длительностью заболевания. Вестн. дерматол. венерол. 2001; (4): 46-50
  34. Корепанова М.В., Коробейникова Э.А., Крюкова О.И. Клиническая эффективность цефтриаксона в терапии ранних форм сифилиса. Клин. дерматол. венерол. 2011; (1): 55-58
  35. Мишанов В.Р. Сравнительная оценка отдаленных результатов лечения пациентов с ранними формами сифилиса бензил-пенициллина натриевой солью и бензатина бензилпенициллином в Нижегородской области. Совр. пробл. дерматовенерол. иммунол. врач. косметол. 2012; (1): 17-22
  36. Красносельских Т.В., Соколовский Е.В., Радовицкая Г.В. и др. Современное состояние проблемы серологической резистентности после лечения сифилиса (по материалам кожно-венерологических диспансеров г. Санкт-Петербурга). Журн. дерматовенерол. косметол. 2000; (2): 41-50
  37. Красносельских Т.В. Определение спектра и соотношения антитрепонемных антител в диагностике приобретенного сифилиса: Автореф. дис. ... канд. мед. наук. СПб, 1998; 21
  38. Nathan L., Bawdon R.E., Sidawi J.E. et al. Penicillin levels following the administration of benzathine penicillin G in pregnancy. Obstet Gynecol 1993; 82 (3): 338-342.
  39. Marra C.M., Maxwell C.L., Tantalo L. et al. Normalization of cerebrospinal fluid abnormalities after neurosyphilis therapy: does HIV status matter? Clin Infect Dis 2004; 38 (7): 1001-1006.
  40. Ghanem K.G., Moore R.D., Rompalo A.M. et al. Neurosyphilis in a clinical cohort of HIV-1-infected patients. AIDS 2008; 22 (10): 1145-1151.
  41. Douglas J.M. Jr. Penicillin treatment of syphilis: clearing away the shadow on the land. JAMA 2009; 301 (7): 769-771.
  42. Stamm L.V. Global challenge of antibiotic-resistant Treponema pallidum. Antimicrob Agents Chemother 2010; 54 (2): 583-589.
  43. Macy E., Poon K.-Y. T. Self-reported antibiotic allergy incidence and prevalence: age and sex effects. Am J Med 2009; 122 (8): 778.e1-778.e7.
  44. Albin S., Agarwal S. Prevalence and characteristics of reported penicillin allergy in an urban outpatient adult population. Allergy Asthma Proc 2014; 35 (6): 489-494.
  45. Ahmed K.A., Fox S.J., Frigas E., Park M.A. Clinical outcome in the use of cephalosporins in pediatric patients with a history of penicillin allergy. Int Arch Allergy Immunol 2012; 158 (4): 405-410.
  46. Marra C.M., Boutin P., McArthur J.C. et al. A pilot study evaluating ceftriaxone and penicillin G as treatment agents for neurosyphilis in human immunodeficiency virus-infected individuals. Clin Infect Dis 2000; 30 (3): 540-544.
  47. Dowell M.E., Ross P.G., Musher D.M. et al. Response of latent syphilis or neurosyphilis to ceftriaxone therapy in persons infected with human immunodeficiency virus. Am J Med 1992; 93: 481-488.
  48. Hook E.W., 3rd, Roddy R.E., Handsfield H.H. Ceftriaxone therapy for incubating and early syphilis. J Infect Dis 1988; 158 (4): 881-884.
  49. Park M.A., Koch C.A., Klemawesch P. et al. Increased adverse drug reactions to cephalosporins in penicillin allergy patients with positive penicillin skin test. Int Arch Allergy Immunol 2010; 153 (3): 268-273.
  50. Pichichero M.E., Casey J.R. Safe use of selected cephalosporins in penicillin-allergic patients: a meta-analysis. Otolaryngol Head Neck Surg 2007; 136 (3): 340-347.
  51. Ghanem K.G., Erbelding E.J., Cheng W.W., Rompalo A.M. Doxycycline compared with benzathine penicillin for the treatment of early syphilis. Clin Infect Dis 2006; 42 (6): e45-e49.
  52. Wong T., Singh A.E., De P. Primary syphilis: serological treatment response to doxycycline/ tetracycline versus benzathine penicillin. Am J Med 2008; 121 (10): 903-908.
  53. Tsai J.C., Lin Y.H., Lu P.L. et al. Comparison of serological response to doxycycline versus benzathine penicillin G in the treatment of early syphilis in HIV-infected patients: a multi-center observational study. PLoS One 2014; 9 (10): e109813.
  54. Кубанова А.А., Кубанов А.А., Фриго Н.В. и др. Первый опыт молекулярного типирования и определения антибиотикорезистентности штаммов возбудителя сифилиса Treponema pallidum в Российской Федерации. Вестн. дерматол. венерол. 2013; (3): 34-46
  55. Лосева О.К., Скопинцева Д.А., Николенко Ю.А. и др. Об эффективности доксициклина при лечении больных ранними формами сифилиса. Вестн. дерматол. венерол. 2004; (6): 57
  56. Katz K.A., Klausner J.D. Azithromycin resistance in Treponema pallidum. Curr Opin Infect Dis 2008; 21 (1): 83-91.
  57. Hook E.W. 3rd, Behets F., Van Damme K. et al. A phase III equivalence trial of azithromycin versus benzathine penicillin for treatment of early syphilis. J Infect Dis 2010; 201 (11): 1729-1735.
  58. Riedner G.M., Rusizoka J., Todd J. et al. Singledose azithromycin versus penicillin G benzathine for the treatment of early syphilis. N Engl J Med 2005; 353 (12): 1236-1244.
  59. Bai Z.G., Yang K.H., Liu Y.L. et al. Azithromycin vs. benzathine penicillin G for early syphilis: a meta-analysis of randomized clinical trials. Int J STD AIDS 2008; 19 (4): 217-221.
  60. Машкиллейсон А.Л., Кутин С.А., Гомберг М.А. и др. Результаты четырехлетнего опыта применения сумамеда при раннем сифилисе. ЗППП 1996; (3): 39
  61. Centers for Disease Control and Prevention. Brief report: azithromycin treatment failures in syphilis infections - San Francisco, California, 2002-2003. MMWR Morb Wkly Rep, 2004; 53: 197-198.
  62. Mitchell S.J., Engelman J., Kent C.K. et al. Azithromycin resistant syphilis infection: San Francisco, California, 2000-2004. Clin Infect Dis 2006; 42 (3): 337-345.
  63. Lukehart S.A., Gordones C., Molini B.J. et al. Macrolide resistance in Treponema pallidum in the United States and Ireland. N Engl J Med 2004; 351 (2): 154-158.
  64. Zhou P., Li K., Lu H. et al. Azithromycin treatment failure among primary and secondary syphilis patients in Shanghai. Sex Transm Dis 2010; 37 (11): 726-729.
  65. Chen X.S., Yin Y.P., Wei W.H. et al. High prevalence of azithromycin resistance to Treponema pallidum in geographically different areas in China. Clin Microbiol Infect 2013; 19 (10): 975-979.
  66. Kingston A.A., Vujevich J., Shapiro M. et al. Seronegative secondary syphilis in 2 patients coinfected with human immunodeficiency virus. Arch Dermatol 2005; 141 (4): 431-433.
  67. Symptomatic early neurosyphilis among HIV-positive men who have sex with men - four cities, United States, January 2002-June 2004. MMWR 2007; 56 (25): 625-628.
  68. Marra C.M., Maxwell C.L., Smith S.L. et al. Cerebrospinal fluid abnormalities in patients with syphilis: association with clinical and laboratory features. J Infect Dis 2004; 189 (3): 369-376.
  69. Stoner B.P. Current controversies in the management of adult syphilis. Clin Infect Dis 2007; 44 Suppl 3: S130-146.
  70. Ghanem K.G., Moore R.D., Rompalo A.M. et al. Antiretroviral therapy is associated with reduced serologic failure rates for syphilis among HIV-infected patients. Clin Infect Dis 2008; 47 (2): 258-265.
  71. Marra C.M., Maxwell C.L., Tantalo L.C. et al. Normalization of serum rapid plasma reagin titer predicts normalization of cerebrospinal fluid and clinical abnormalities after treatment of neurosyphilis. Clin Infect Dis 2008; 47 (7): 893-899.
  72. Alexander J.M., Sheffield J.S., Sanchez P.J. et al. Efficacy of treatment for syphilis in pregnancy. Obstet Gynecol 1999; 93 (1): 5-8.
  73. Walker G.J. Antibiotics for syphilis diagnosed during pregnancy. Cochrane Database Syst Rev 2001; 3: CD001143.
  74. Borisenko K.K., Loseva O.K., Dolya O.V. On the treatment of syphilis in pregnancy. ZPPP 1997; 5: 58-60. [Борисенко К.К., Лосева О.К., Доля О.В. К вопросу о лечении сифилиса у беременных. ЗППП 1997; (5): 58-60.]
  75. Boot J.M., Oranje A.P., de Groot R. Congenital syphilis. Int J STD AIDS 1992; 3 (3): 161-167.
  76. Wendel G.D., Sheffield J.S., Hollier L.M. et al. Treatment of syphilis in pregnancy and prevention of congenital syphilis. Clin Infect Dis 2002; 35 (Suppl 2): S200-S209.
  77. Donders G.G., Desmyter J., Hooft P., Dewet G.H. Apparent failure of one injection of benzathine penicillin G for syphilis during pregnancy in human immunodeficiency virus-seronegative African women. Sex Transm Dis 1997; 24 (2): 94-101.
  78. Zhu L., Qin M., Du L. et al. Maternal and congenital syphilis in Shanghai, China, 2002 to 2006. Int J Infect Dis 2010; 14 (Suppl 3): e45-48.
  79. Temmerman M., Gichangi P., Fonck K. et al. Effect of a syphilis control programme on pregnancy outcome in Nairobi, Kenya. Sex Transm Inf 2000; 76 (2): 117-121.
  80. Conover C.S., Rend C.A., Miller G.B. Jr, Schmid G.P. Congenital syphilis after treatment of maternal syphilis with a penicillin regimen exceeding CDC guidelines. Infect Dis Obstet Gynecol 1998; 6 (3): 134-137.
  81. Иванов А.М. Оптимизация серологической диагностики сифилиса: Автореф. дис.. д-ра мед. наук. СПб, 2006.
  82. Ходосевич Е.В. Клинико-лабораторные особенности сифилиса у беременных в современных условиях: Автореф. дис.. канд. мед. наук. СПб, 2004; 22.
  83. Satti K.F., Ali S.A., Weitkamp J.-H. Congenital Infections, Part 2: Parvovirus, Listeria, Tuberculosis, Syphilis, and Varicella. NeoReviews 2010; 11 (12): e681-e695
  84. Chauhan M., Serisha B., Sankar K.N. et al. Audit of the use of benzathine penicillin, post-treatment syphilis serology and partner notification of patients with early infectious syphilis. Int J STD AIDS 2006; 17 (3): 200-202
  85. Катунин Г.Л., Рубцов А.Б. Анализ отдаленных результатов лечения больных сифилисом с сохраняющимися показателями нетрепонемных серологических тестов препаратом цефтриаксон. Вестн. дерматол. венерол. 2014; (1): 45-52
  86. Ren R.X., Wang L.N., Zheng H.Y., Li J. No improvement in serological response among serofast latent patients retreated with benzathine penicillin. Int J STD AIDS 2015 Feb 16. pii: 0956462415573677. [Epub ahead of print]

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