Current Ceftriaxone Dosing for Gonorrhea Treatment
The recommended dose of ceftriaxone for uncomplicated gonorrhea is now 500 mg IM as a single dose, not 250 mg—this represents an important update from previous guidelines. 1, 2
Evolution of Dosing Recommendations
The ceftriaxone dose for gonorrhea has increased over time in response to antimicrobial resistance patterns:
- Historical dosing (1993-2010): 125 mg IM was the recommended dose, with 250 mg also considered safe and effective 3
- 2010-2020: 250 mg IM became the standard recommendation 1
- Current (2020-present): 500 mg IM is now the recommended dose 1, 2
Rationale for the 500 mg Dose
The increase to 500 mg was driven by several key factors:
- Antimicrobial stewardship concerns: The previous dual therapy with azithromycin 1 g showed a rapid rise in azithromycin resistance (nearly 5% of isolates with elevated MICs by 2018), prompting reevaluation of the treatment strategy 1, 2
- Ceftriaxone MIC stability: While ceftriaxone MICs have remained stable in the United States (<0.1% with "alert value" MIC >0.25 mcg/mL), the higher dose provides greater therapeutic reserve against potential resistance 2
- Pharmacodynamic data: Recent studies demonstrate that 500 mg provides superior eradication, particularly for pharyngeal infections and low-level resistant strains 4
Current Treatment Regimen
For uncomplicated urogenital, anorectal, and pharyngeal gonorrhea:
- Ceftriaxone 500 mg IM as a single dose 1, 2
- PLUS doxycycline 100 mg orally twice daily for 7 days if chlamydial coinfection has not been excluded 1, 2
This represents a shift away from dual therapy with azithromycin 1 g to doxycycline for chlamydia coverage, addressing antimicrobial stewardship while maintaining effective treatment 1, 2.
Critical Clinical Considerations
Pharyngeal infections require special attention:
- Pharyngeal gonorrhea is significantly more difficult to eradicate than urogenital or anorectal infections 5, 6
- The 500 mg dose provides improved efficacy for pharyngeal sites compared to lower doses 1, 2
- Alternative oral regimens (cefixime) have poor pharyngeal efficacy and should be avoided when pharyngeal infection is suspected 5, 6
The 250 mg dose is outdated:
- While FDA labeling still lists 250 mg for uncomplicated gonococcal infections 7, this reflects older guidance
- Current CDC recommendations supersede FDA labeling and should be followed in clinical practice 1, 2
Alternative Regimens (When Ceftriaxone Unavailable)
If ceftriaxone is not available:
- Cefixime 400 mg orally once PLUS azithromycin 1 g orally once 5, 8
- Mandatory test-of-cure at 1 week is required with this regimen due to declining cefixime effectiveness 5, 8
Common Pitfall to Avoid
Never use the 250 mg dose for current gonorrhea treatment—this outdated recommendation does not reflect current antimicrobial resistance patterns and antimicrobial stewardship principles. The 500 mg dose is now standard practice and provides better protection against treatment failure, particularly for pharyngeal infections 1, 2.