Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2012 Jun 13;2012(6):CD007270.
doi: 10.1002/14651858.CD007270.pub2.

Azithromycin versus penicillin G benzathine for early syphilis

Zheng Gang Bai  1 , Baoxi Wang, Kehu Yang, Jin Hui Tian, Bin Ma, Yali Liu, Lei Jiang, Qiong Yan Gai, Xiaodong He, Youping Li
Affiliations
Meta-Analysis

Azithromycin versus penicillin G benzathine for early syphilis

Zheng Gang Bai et al. Cochrane Database Syst Rev. .

Abstract

Background: Syphilis is a complex systemic disease caused by a spirochete, Treponema pallidum. The World Health Organization estimates that at least 12 million people worldwide are currently infected with syphilis. In this review we compared two current standards of treatment for early syphilis, benzathine benzylpenicillin (penicillin G) and azithromycin.

Objectives: To evaluate the efficacy and safety of azithromycin versus benzathine penicillin (penicillin G) for early syphilis.

Search methods: We searched the following databases using the search terms detailed in Appendix 1: the Cochrane Sexually Transmitted Diseases Group Specialized Register (July 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) published in The Cochrane Library (Issue 7 2011), MEDLINE (1948 to July 2011), EMBASE (1980 to July 2011), PsycINFO (1806 to July 2011) and the Chinese Biological Medicine Literature Database (CBM) (1978 to 2011). The search was not limited by language.

Selection criteria: Randomized controlled trials comparing azithromycin with benzathine penicillin G at any dose for the treatment of early syphilis.

Data collection and analysis: Two review authors independently applied the inclusion criteria to potential studies, with any disagreements resolved by discussion. The risk of bias of each study was assessed by the same two review authors. We pooled data using an odds ratio (OR).

Main results: Three studies (generating four eligible study comparisons) were included. One study is ongoing. There was no statistically significant difference between azithromycin and benzathine penicillin treatment in the odds of cure (OR 1.04, 95% CI 0.69 to 1.56); nor any difference at three months (OR 0.97, 95% CI 0.62 to 1.50), six months (OR 1.09, 95% CI 0.76 to 1.54) or nine months (OR 1.45, 95% CI 0.46 to 6.42). Subgroup analysis by primary and latent syphilis and by dose of azithromycin (2 g and 4 g) did not explain the variation between the study results. The reporting of computed mild to tolerated adverse events, from two included trials, indicated no statistically significant difference between azithromycin and benzathine penicillin (OR 1.43, 95% CI 0.42 to 4.95), although with a high level of heterogeneity (P = 0.05, I(2) = 74%).

Authors' conclusions: Differences in the odds of cure did not reach statistical significance when azithromycin was compared with benzathine penicillin for the treatment of early syphilis. No definitive conclusion can be made regarding the relative safety of benzathine penicillin G and azithromycin for early syphilis. Further studies on the utility of benzathine penicillin G for early syphilis are warranted.

PubMed Disclaimer

Conflict of interest statement

None declared

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Forest plot of comparison: 1 Cure rate, outcome: 1.1 Cure rate.
4
4
Forest plot of comparison: 1 Cure rate, outcome: 1.2 Cumulative cure rate.
5
5
Forest plot of comparison: 2 Subgroup analysis: syphilis stage, outcome: 2.1 Cure rate (syphilis stage).
6
6
Forest plot of comparison: 3 Subgroup analysis: dosage of azithromycin, outcome: 3.1 cure rate ‐different dosage.
7
7
Forest plot of comparison: 4 Adverse effects, outcome: 4.1 Adverse events.
1.1
1.1. Analysis
Comparison 1 Cure rate, Outcome 1 Cure rate.
1.2
1.2. Analysis
Comparison 1 Cure rate, Outcome 2 Cumulative cure rate.
2.1
2.1. Analysis
Comparison 2 Subgroup analysis: syphilis stage, Outcome 1 Cure rate (syphilis stage).
3.1
3.1. Analysis
Comparison 3 Subgroup analysis: dosage of azithromycin, Outcome 1 cure rate ‐different dosage.
4.1
4.1. Analysis
Comparison 4 Adverse effects, Outcome 1 Adverse events.
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD007270

Similar articles

See all similar articles

Cited by

References

References to studies included in this review

Eward 2010 {published data only}
    1. Hook EW 3rd, Behets F, 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. Journal of Infectious Diseases 2010;201(11):1729‐35. - PubMed
Hook 2002 {published data only}
    1. Hook EW III, Martin DH, Stephens J. A randomised, comparative pilot study of azithromycin versus benzathine penicillin G for treatment of early syphilis. Sexually Transmitted Diseases 2002;29:486‐90. - PubMed
Riedner 2005 {published data only}
    1. Riedner G, Rusizoka M, Todd J, Riedner MD. Single‐dose azithromycin versus penicillin G benzathine for the treatment of early syphilis. New England Journal of Medicine 2005;353:1236‐44. - PubMed

References to studies excluded from this review

Ennis 1996 {published data only}
    1. Ennis DM, Stephens JG, et al. A randomized comparative trial of azithromycin and benzathine penicillin G for prevention of syphilis in exposed patients. Clinical Infectious Diseases 1996;23:916.
Hook 1999 {published data only}
    1. Hook EW 3rd, Stephens J, Ennis DM. Azithromycin compared with penicillin G benzathine for treatment of incubating syphilis. Annals of Internal Medicine 1999;131(6):434‐7. - PubMed
Huang 2003 {published data only}
    1. Huang X. Benzathine, azithromycin, ceftriaxone for early syphilis. Guangxi Medicine 2003;25:1869.
Kiddugavu 2005 {published data only}
    1. Kiddugavu MG, Kiwanuka N, Wawer MJ. Effectiveness of syphilis treatment using azithromycin and/or benzathine penicillin in Rakai, Uganda. Sexually Transmitted Diseases 2005;32:1‐6. - PubMed
Pan 2005 {published data only}
    1. Pan XC. Effect survey of three different drugs for early syphilis. Med Study Clin China 2005;5:3‐5.
Rolfs 1997 {published data only}
    1. Rolfs RT, Joesoef MR, Hendershot EF, Rompalo AM, Augenbraun MH, Chiu M, 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. New England Journal of Medicine 1997;337(5):307‐14. - PubMed
Yang 2005 {published data only}
    1. Yang JW. Effect analysis of azithromycian versus penicillin G for early syphilis. Journal of Shanxi Medical College for Continuing Education 2005;15:41‐2.

References to ongoing studies

Hook 2008 {unpublished data only}
    1. Hook EW, Stephens J, Ennis DM. Azithromycin compared with penicillin G benzathine for treatment of incubating syphilis. Annals of Internal Medicine 1999;131:434‐7. - PubMed

Additional references

Adler 1995
    1. Adler MW. ABC of Sexually Transmitted Diseases. 3rd Edition. London: BMJ Publishing Group, 1995.
Altman 2003
    1. Altman DG, Bland JM. Interaction revisited: the difference between two estimates. BMJ 2003;326:219. - PMC - PubMed
Bardy 2005
    1. Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter–defibrillator for congestive heart failure. New England Journal of Medicine 2005;352:225‐37. - PubMed
Blandford 2003
    1. Blandford JM, Gift TL. The cost‐effectiveness of single‐dose azithromycin for treatment of incubating syphilis. Sexually Transmitted Diseases 2003;30(6):502‐8. - PubMed
Higgins 2011
    1. Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. www.cochrane‐handbook.org. The Cochrane Collaboration, 2011.
Hook 1989
    1. Hook III EW. Treatment of syphilis: current recommendations, alternatives, and continuing problems. Reviews of Infectious Diseases 1989; Vol. 11 Suppl 6:1511‐7. - PubMed
Hook 1992
    1. Hook III EW, Marra CM. Acquired syphilis in adults. New England Journal of Medicine 1992;326(16):1060‐9. - PubMed
Hutchinson 1990
    1. Hutchinson CM, Hook EW. Syphilis in adults. Medical Clinics of North America 1990;74:1389‐416. - PubMed
Idsoe 1972
    1. Idsoe O, Guthe T, Willcox RR. Penicillin in the treatment of syphilis: the experience of three decades. Bulletin of World Health Organization. 1972; Vol. 47 Suppl:1‐68. - PMC - PubMed
Katz 2008
    1. Katz KA, Klausner JD. Azithromycin resistance in Treponema pallidum. Current Opinion in Infectious Diseases 2008;21(1):83‐91. - PubMed
Lau 2002
    1. Lau CY, Qureshi AK. Azithromycin versus doxycycline for genital chlamydial infections: A meta‐analysis of randomized clinical trials. Sexually Transmitted Diseases 2002;29(9):497‐502. - PubMed
Lukehart 1990
    1. Lukehart SA, Fohn MJ, Baker‐Zander SA. Efficacy of azithromycin for therapy of active syphilis in the rabbit model. Journal of Antimicrobial Chemotherapy 1990;25:91‐9. - PubMed
Lukehart 2004
    1. Lukehart SA, Godornes C, Molini BJ, Patricia Sonnett MS, Hopkins S, Mulcahy F, et al. Macrolide resistance in Treponema pallidum in the United States and Ireland. New England Journal of Medicine 2004;351(2):154‐8. - PubMed
McCraken 1974
    1. McCraken GH, Kaplan JM. Penicillin treatment for congenital syphilis. A critical reappraisal. JAMA 1974;228(7):855‐8. - PubMed
Rolfs 1995
    1. Rolfs RT. Treatment of syphilis, 1993. Clinical Infectious Diseases 1995;20(1):23‐38. - PubMed
Thomas 1949
    1. Thomas EW. Rapid treatment of syphilis with penicillin; penicillin in prenatal and infantile syphilis. Bulletin of the World Health Organization. Supplement 1949;2(2):249‐55. - PMC - PubMed
Tucker 1949
    1. Tucker HA. Penicillin syphilotherapy administered during pregnancy: a study of 149 pregnancies during which penicillin was given for early maternal syphilis. American Journal of Medical Sciences 1949;217(2):157‐61. - PubMed
Verdon 1994
    1. Verdon MS, Handsfield HH, Johnson RB. Pilot study of azithromycin for treatment of primary and secondary syphilis. Clinical Infectious Diseases 1994;19:486‐8. - PubMed
Walker 2001
    1. Walker GJA. Antibiotics for syphilis diagnosed during pregnancy. Cochrane Database of Systematic Reviews 2001, issue 2. [Art.No.: CD001143 DOI: 10.1002/14651858.CD001143] - PMC - PubMed
Walker 2007
    1. Walker GJ, Walker DG. Congenital syphilis: a continuing but neglected problem. Seminars in Fetal & Neonatal Medicine 2007;12(3):198‐206. - PubMed
WHO 2001
    1. World Health Organization. Global prevalence and incidence of selected curable sexually transmitted infections overview and estimates. WHO/HIV_AIDS/2001.02 and WHO/CDS/CSR/EDC/2001.10. Geneva:WHO, 2001 2001.
Willcox 1981
    1. Willcox. Treatment of syphilis. Bulletin of the World Health Organization 1981;59(5):655‐63. - PMC - PubMed

References to other published versions of this review

Bai 2008
    1. Zheng‐Gang B, Yang KH, Liu YL, Tian JT, Bin M. Azithromycin vs. benzathine penicillin G for early syphilis:a meta‐analysis of randomized clinical trials. International Journal of STD & AIDS 2008;19:217‐21. - PubMed

MeSH terms

LinkOut - more resources