Azithromycin, an effective treatment for early syphilis, works well in those with HIV

Michael Carter
Published: 22 September 2005

A single dose of an oral antibiotic provides treatment for early and latent syphilis that is equivalent to the currently recommended penicillin injection, according to a study reported in the September 22nd edition of the New England Journal of Medicine. The investigators found that a single oral dose consisting of 2g of azithromycin (Zithromax) achieved cure rates for syphilitic chancres comparable to penicillin G benzathine, and that individuals who were treated with azithromycin had cure rates at three, six, and nine months equivalent to those seen in patients treated with penicillin injections.

What’s more, over 50% of the study population were HIV-positive and azithromycin was found to be as effective a treatment for syphilis in these patients as injections with penicillin. However, the investigators note that a strain of azithromycin-resistant syphilis has been found in HIV-positive individuals in the United States and Ireland.

Many treatment guidelines recommend a single intramuscular injection with 2.4 million units (MU) of penicillin G benzathine for early syphilis. The main advantages of this treatment are low cost and a low risk of resistance. However, the injection can be painful, trained healthcare staff are required to administer them, many patients report an allergy to penicillin, and in low income settings, there is a risk that blood-borne organisms, including HIV, will be transmitted if injecting equipment is reused.

Azithromycin is a macrolide antibiotic. It has a 68 hour half-life in tissue and has been shown to be an effective treatment for sexually transmitted infections including Chlamydia and gonorrhoea (although current UK treatment guidelines do not recommend its use for this infection). Pilot studies suggest that it could also provide a safe and effective treatment for syphilis. Investigators therefore conducted a randomised controlled trial to see if a single 2g dose of azithromycin was equivalent to the standard treatment of a 2.4MU penicillin G benzathine injection as a treatment for early syphilis.

The study took place between 2000 and 2003 and involved 328 individuals with early or latent syphilis in Tanzania. A total of 25 individuals had early syphilis, indicated by the presence of chancres, the remaining patients had latent syphilis. Patients were equally randomised to receive azithromycin or penicillin.

Average age of the patients was 27 years, 72% were women and 52% were HIV-positive.

Of the 25 patients with early syphilis, the chancres completely resolved within two weeks of treatment in 63% of patients and were in the process of healing in the remaining patients. There were no significant differences in these rates between the azithromycin and penicillin arms. By three months, the chancres had completely resolved in all the patients.

Cure rates, indicated by looking at the amount of syphilis in the blood using PCR testing, were compared between the two arms of the study at three, six and nine months. At each point equivalent numbers of azithromycin-treated and penicillin-treated patients had been cured (month three, 59% versus 60%; month six, 86% versus 82%; month nine, 98% versus 95%).

Azithromycin and penicillin worked equally well in HIV-positive patients, with comparable cure rates achieved at months three (60% versus 66%), six (81% versus 81%) and nine (94% versus 95%).

Side-effects reported by patients treated with azithromycin included nausea (9%), stomach pain (4%), diarrhoea (1%) and vomiting (1%).

“This randomised, controlled trial has provided clear evidence that a single, 2g dose of azithromycin is as effective as a 2.4MU dose of penicillin G benazathine for the treatment of early syphilis”, comment the investigators.

Although none of the patients in the study had syphilis which was resistant to azithromycin, the investigators note that a study in the US and Ireland found that a strain of the infection (the Street 14 strain) with a naturally occurring mutation which confers resistance to azithromycin has been seen in HIV-positive gay men.

The investigators comment on the high cure rates seen in HIV-positive patients irrespective of which treatment they received. There is however concern that HIV-positive patients may be at increased risk of neurosyphilis and the investigators did not obtain samples of cerebrospinal fluid to rule this out.

“Our findings support the wider use of [azithromycin] in syphilis control programs”, conclude the investigators.


Riedner G et al. Single-dose azithromycin versus penicillin G benzathine for the treatment of early syphilis. N Eng J Med 353: 1236 – 1244, 2005.

Community Consensus Statement on Access to HIV Treatment and its Use for Prevention

Together, we can make it happen

We can end HIV soon if people have equal access to HIV drugs as treatment and as PrEP, and have free choice over whether to take them.

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