Single-dose azithromycin versus penicillin G benzathine for the treatment of early syphilis.
Open accessAbstract
BACKGROUND: Pilot studies suggest that a single, 2-g oral dose of azithromycin may be an alternative to a 2.4-MU intramuscular dose of penicillin G benzathine in the prevention and treatment of syphilis. We evaluated the efficacy of treatment with azithromycin in a developing country. METHODS: A total of 328 subjects, 25 with primary and 303 with high-titer (a titer of at least 1:8 on a rapid plasmin reagin [RPR] test) latent syphilis, were recruited through screening of high-risk populations in Mbeya, Tanzania, and randomly assigned to receive 2 g of azithromycin orally (163 subjects) or 2.4 million units of penicillin G benzathine intramuscularly (165 subjects). The primary outcome was treatment efficacy, with cure defined serologically (a decline in the RPR titer of at least two dilutions by nine months after treatment) and, in primary syphilis, by epithelialization of ulcers within one or two weeks. RESULTS: The average age of participants was 27.0 years, 235 (71.6 percent) were female, and 171 (52.1 percent) were seropositive for human immunodeficiency virus. Cure rates were 97.7 percent (95 percent confidence interval, 94.0 to 99.4) in the azithromycin group and 95.0 percent (95 percent confidence interval, 90.6 to 97.8) in the penicillin G benzathine group (95 percent confidence interval for the difference, -1.7 to 7.1 percent), achieving prespecified criteria for equivalence. Cure rates were also similar three and six months after treatment in the two groups and in all subgroups. Cure rates at three months were 59.4 percent (95 percent confidence interval, 51.8 to 67.1) in the azithromycin group and 59.5 percent (95 percent confidence interval, 51.8 to 67.3) in the penicillin G benzathine group and at six months were 85.5 percent (95 percent confidence interval, 79.4 to 90.6) and 81.5 percent (95 percent confidence interval, 74.8 to 87.4), respectively. CONCLUSIONS: Single-dose oral azithromycin is effective in treating syphilis and may be particularly useful in developing countries in which the use of penicillin G benzathine injections is problematic. However, recent reports of azithromycin-resistant Treponema pallidum in the United States indicate the importance of continued monitoring for resistance.
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Azithromycin as a single 2-g oral dose has been effective for treating primary and secondary syphilis among certain populations.
“Azithromycin as a single 2-g oral dose has been effective for treating primary and secondary syphilis among certain populations (602,604,605).”
From Sexually Transmitted Infections Treatment Guidelines, 2021 (2021) · cites this paper as [604]
The study reports that a single 2-g oral dose of azithromycin was effective for early syphilis in its Tanzanian study population, including participants with primary syphilis (statistical analysis). But the same section states that there were no PCR-confirmed cases of secondary syphilis, so this paper does not establish effectiveness for that stage. (LLM, conf=0.93)
Experimental — accuracy not yet measuredAzithromycin has shown good treponemicidal activity in animal studies and several controlled studies.
“Azithromycin has shown good treponemicidal activity in animal studies and several controlled studies.100,101”
From BASHH UK guidelines for the management of syphilis 2024 (2024) · cites this paper as [100]
The introduction (p. 1237) describes two pilot studies suggesting azithromycin may prevent or treat syphilis, and the abstract reports favorable results from this paper’s randomized controlled trial. Our copy does not report animal studies or directly establish treponemicidal activity in animals, so that part of the claim is unsupported. (LLM, conf=0.86)
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- Authors
- Riedner, G., Rusizoka, M., Todd, J., Maboko, L., Hoelscher, M., Mmbando, D., Samky, E., Lyamuya, E., Mabey, D., Grosskurth, H., & Hayes, R.
- Affiliations
- London School of Hygiene & Tropical Medicine (GB)
- Muhimbili University of Health and Allied Sciences (TZ)
- Uganda Virus Research Institute (UG)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2005-09-22
- Volume
- 353
- Issue
- 12
- Pages
- 1236-1244
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2074516129
- Cited by
- 296
- References
- 12
- Citations by year
- 2026: 7 · 2025: 4 · 2024: 9 · 2023: 11 · 2022: 3 · 2021: 11 · 2020: 14 · 2019: 10 · 2018: 7 · 2017: 11 · 2016: 13 · 2015: 16 · 2014: 14 · 2013: 16 · 2012: 17
- FWCI
- 12.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- Funders
- Wellcome Trust
- Topics
- Health Sciences › Medicine › Physiology › Syphilis Diagnosis and Treatment
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Historical Medical Research and Treatments
- Life Sciences › Immunology and Microbiology › Parasitology › Vector-borne infectious diseases
- Keywords
- early syphilis, azithromycin, benzathine penicillin G, latent syphilis, primary syphilis, treatment efficacy, cure rate, serological cure, HIV coinfection, developing countries
- MeSH terms
- Administration, Oral, Adolescent, Adult, Anti-Bacterial Agents, Developing Countries, Female, HIV Seropositivity, Humans, Injections, Intramuscular, Male, Penicillin G Benzathine, Syphilis, Proportional Hazards Models, Azithromycin
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