Efficacy of Ceftriaxone Monotherapy Comparable to Dual Therapy for Extragenital Gonorrhea

For men who have sex with men and are diagnosed with extragenital Neisseria gonorrhoeae infection, high-dose ceftriaxone monotherapy was found to be as effective as dual therapy with azithromycin or doxycycline, according to results of a study published in Clinical Infectious Diseases.

Study participants were enrolled from a cohort of men who have sex with men tested for N gonorrhoeae/Chlamydia trachomatis every 3 months in a single-center observational study in Tokyo, Japan. Participants older than 19 years who were diagnosed with extragenital N gonorrhoeae infection between 2017 and 2020 were included and received a single 1-g dose of intravenous ceftriaxone monotherapy. For those diagnosed with a C trachomatis coinfection, dual therapy with a single 1-g dose of azithromycin or doxycycline 100 mg taken orally twice daily for 7 days was administered.

A total of 320 cases were diagnosed; 208 were treated with monotherapy, and 112 were treated with dual therapy. In the monotherapy group, efficacy against total, pharyngeal, and rectal infections was 98.1% (95% CI, 95.2-99.3), 97.8% (95% CI, 93.8-99.4), and 98.6% (95% CI, 92.3-99.9), respectively. In the dual therapy group, efficacy was 95.5% (95% CI, 90.0-98.1) against total infection, 96.1% (95% CI, 86.8-99.3) against pharyngeal infection, and 95.1% (95% CI, 86.5-98.7) against rectal infection. There was no significant difference in corresponding efficacy between groups for total (P =.29), pharyngeal (P =.61), or rectal (P =.34) infections. A total of 9 cases failed treatment, of which 3 were successfully cultured and no resistant mutations to ceftriaxone were detected. Among the cases in which treatment failed, the proportions of monotherapy or dual therapy and rectal and pharyngeal infections were similar.

The researchers report several study limitations, including the inability to control the sample size due to the observational nature of the study, the intravenous dose of 1 g ceftriaxone being one of the highest recommended and different from recently recommended therapies, and the choice of doxycycline as the second agent due to high levels of resistance in N gonorrhoeae.

According to the study authors, although the results of this study showed the similar efficacies of monotherapy and dual therapy options in a real-world setting, there is still a need for randomized controlled trials to clarify the efficacy of these treatment options in settings where resistance to ceftriaxone is a concern.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Aoki T, Mizushima D, Takano M, et al. Efficacy of 1g ceftriaxone monotherapy compared to dual therapy with azithromycin or doxycycline for treating extragenital gonorrhea among men who have sex with men. Clin Infect Dis. Published online May 17, 2021. doi: 10.1093/cid/ciab455