1. Single-Dose Azithromycin versus Penicillin G Benzathine for the Treatment of Early Syphilis Jay Gargus, Department of Biological and Environmental Sciences, University of West Alabama, Livingston, AL 35470 Riedner, G. et al. [eleven other authors]. Single-Dose Azithromycin versus Penicillin G Benzathine for the Treatment of Early Syphilis. The New England Journal of Medicine. Vol. 353: 1236-1244. ABSTRACT Studies suggest that a single, 2 gram oral dose of azithromycin, a macrolide antibiotic, may be an alternative to a 2.4-MU (million units) intramuscular dose of penicillin G benzathine in the prevention and treatment of syphilis. A total of 328 subjects were recruited, 25 with primary syphilis and 303 with high-titer latent syphilis. These subjects were recruited through screening of high-risk populations in Mbeya, Tanzania. Subjects were randomly assigned to receive 2 grams of azithromycin or 2.4 million units of penicillin G benzathine by muscular injection. The principal result was treatment efficacy. Cure rates were 97.7% (95% confidence interval, 94.0 to 99.4) in the azithromycin group and 95% (95% confidence interval, 90.6 to 97.8) in the penicillin G benzathine group. Single dose azithromycin is effective in the treatment of syphilis, however reports of azithromycin-resistant Treponema pallidum indicate the importance of continued monitoring for resistance. INTRODUCTION A single intramuscular injection of 2.4 MU of penicillin G benzathine is the recommended therapy for early syphilis. Advantages of this treatment are its low cost. Disadvantages include pain associated with a deep injection, penicillin allergies, and the need for injection equipment and the medical personnel to administer injections. Also, there are risks of blood-borne infections, such as HIV. The use of an effective, oral, single-dose therapy would surmount the disadvantages associated with injectable penicillin G benzathine. Azithromycin, a macrolide antibiotic with a 68 hour half-life in tissue, was a treatment alternative. The purpose of this experiment was to test the hypothesis that the efficacy of a single, 2 gram oral dose of azithromycin is equal to the standard syphilis treatment of a 2.4 MU injection of penicillin G benzathine. METHODS Subjects were randomly assigned to receive 2 grams of azithromycin orally (163 subjects) or 2.4 MU of penicillin G benzathine by IM injection (165 subjects). People with confirmed syphilis were recruited through screening of high-risk populations in Mbyea Region, Tanzania, including female bar workers, patients with sexually transmitted infections, and traditional-brew sellers. People confirmed with syphilis and those with a reactive rapid plasma reagin (RPR) test at the time of screening were eligible for the study. An RPR test measures antibodies produced by Treponema pallidum, the bacteria that causes syphilis. Participants were reexamined every three months for up to nine months until they were cured. The study was conducted between September 2000 and September 2003. RESULTS The average age of participants was 27 years, 71.6% were female, and 52.1% were seropositive for HIV. Cure was recorded at or before the nine-month follow-up visit in all but 21 subjects. Data on 9 subjects were censored at the three-month follow-up and on 2 at the six-month follow-up visit. Treatment failure was recorded in 10 subjects at the nine-month follow-up visit. In the primary analysis, the cure rates were 97.7% in the azithromycin group and 95% in the penicillin G benzathine group (Fig. 2). Since there was considerable variation between subjects in the timing of follow-up visits, a secondary analysis was performed. In the secondary analysis, the cure rate at nine months in the azithromycin group was 98.3%. The cure rate in the penicillin G benzathine group was 96.5% at nine months. These results support the hypothesis that a 2 gram oral dose of azithromycin is equal to a 2.4 MU injection of penicillin G benzathine for syphilis treatment. Figure 2: Mean cure rates Figure 3: Cure Rates According to Treatment (Panel A), Stage of Syphilis (Panel B), RPR Titer at Baseline (Panel C), and HIV Status (Panel D) Table 1: Cure Rates at the three-, six-, and nine-month follow-up exams. Figure 1: Enrollment and Outcomes CONCLUSIONS This randomized, controlled trial has provided clear evidence that a single, 2 gram dose of azithromycin is as effective as a 2.4 MU dose of penicillin G benzathine for the treatment of early syphilis. Although monitoring for azithromycin resistance will be vital, the results back the wider use of azithromycin therapy in the treatment of syphilis. LITERATURE CITED Riedner, G. et al. [eleven others authors]. Single-Dose Azithromycin versus Penicillin G Benzathine for the Treatment of Early Syphilis. The New England Journal of Medicine. Vol. 353: 1236-1244. http://en.wikipedia.org/wiki/Penicillin http://en.wikipedia.org/wiki/Syphilis