From the Guidelines
Ceftriaxone is now the preferred treatment for gonorrhea due to its superior efficacy compared to cefixime, which has shown decreasing effectiveness over time due to emerging resistance patterns in Neisseria gonorrhoeae. The current recommended regimen is a single 250 mg intramuscular injection of ceftriaxone, which provides more reliable cure rates than cefixime 1. Cefixime (400 mg oral dose) was previously used but has shown limited efficacy for treatment of pharyngeal gonorrhea and demonstrates declining effectiveness for urogenital gonorrhea due to rising cefixime MICs, particularly in the West and among men who have sex with men (MSM) 1.
Key Considerations
- Ceftriaxone achieves higher and more sustained blood and tissue levels, allowing it to overcome the minimum inhibitory concentrations needed to kill even less susceptible strains of Neisseria gonorrhoeae 1.
- The use of a second antimicrobial, such as azithromycin 1 g orally as a single dose or doxycycline 100 mg orally twice daily for 7 days, is recommended for administration with ceftriaxone to improve treatment efficacy and potentially delay emergence and spread of resistance to cephalosporins 1.
- All patients treated for gonorrhea should be tested for other sexually transmitted infections, particularly chlamydia, and should abstain from sexual activity for 7 days after treatment completion.
- Partners from the previous 60 days should also be evaluated and treated to prevent reinfection.
Alternative Regimens
For patients with severe beta-lactam allergies who cannot receive ceftriaxone, alternative regimens may be considered, but these should be chosen with caution and in consultation with a specialist, as the effectiveness of these alternatives may vary and the risk of resistance development is a concern 1.
From the Research
Efficacy of Cefixime vs Ceftriaxone for Gonorrhea
- The efficacy of cefixime versus ceftriaxone for treating gonorrhea has been compared in several studies 2, 3, 4, 5.
- A study published in 1991 found that single-dose cefixime (400 mg or 800 mg) was as effective as ceftriaxone (250 mg) in treating uncomplicated gonorrhea, with cure rates of 96% and 98% for cefixime and 98% for ceftriaxone 3.
- Another study published in 2022 found that a single 1 g intravenous dose of ceftriaxone plus doxycycline was superior to a single 800 mg oral dose of cefixime plus doxycycline for the treatment of Neisseria gonorrhoeae and Chlamydia trachomatis co-infection, with success rates of 96.7% and 95.3% respectively 4.
- However, a study published in 2024 found that the prevalence of cefixime-resistant Neisseria gonorrhoeae in Melbourne, Australia was 6.3%, which exceeds the threshold of the 5% resistance level recommended by the World Health Organization, suggesting that cefixime treatment may have limited benefits in this region 6.
- In terms of safety, all three regimens (cefixime, ceftriaxone, and azithromycin) were well tolerated in the studies, with gastrointestinal side effects being the most common adverse event reported 2, 3, 4.
Comparison of Cefixime and Ceftriaxone
- Cefixime and ceftriaxone have been compared in several studies, with ceftriaxone being the more commonly used treatment for gonorrhea 2, 3, 4, 5.
- Ceftriaxone has been shown to be effective in treating uncomplicated gonorrhea, with cure rates of 97.7% to 99.1% 2, 3, 5.
- Cefixime has also been shown to be effective, with cure rates of 96% to 98% 3, 4.
- However, the prevalence of cefixime-resistant Neisseria gonorrhoeae is increasing, which may limit the effectiveness of cefixime treatment in some regions 6.