Gonorrhea Treatment
For uncomplicated gonorrhea in adults, treat with ceftriaxone 500 mg intramuscularly as a single dose, plus doxycycline 100 mg orally twice daily for 7 days if chlamydial coinfection has not been excluded. 1, 2
First-Line Recommended Regimen
The current standard treatment consists of:
- Ceftriaxone 500 mg IM as a single dose
- Plus doxycycline 100 mg orally twice daily for 7 days (if Chlamydia trachomatis infection not ruled out)
This represents an evolution from the 2012 dual therapy recommendation of ceftriaxone 250 mg plus azithromycin 1 g. The change was driven by rising azithromycin resistance (nearly 5% of isolates by 2018 showing elevated MICs ≥2.0 mcg/mL) and antimicrobial stewardship concerns, while ceftriaxone MICs have remained stable in the United States with <0.1% showing alert values 1, 2.
Treatment by Anatomic Site
The 500 mg ceftriaxone dose is effective for:
- Urogenital infections (cervix, urethra)
- Anorectal infections
- Pharyngeal infections
All sites receive the same regimen 1, 2.
Alternative Regimens
If Ceftriaxone Unavailable
- Cefixime 400 mg orally as a single dose
- Plus azithromycin 1 g orally as a single dose (preferred over doxycycline)
- Requires test-of-cure in 1 week 3
Critical caveat: Cefixime is no longer recommended as first-line due to declining susceptibility and limited efficacy for pharyngeal gonorrhea 3.
If Severe Cephalosporin Allergy
- Azithromycin 2 g orally as a single dose
- Requires test-of-cure in 1 week 3
Important limitation: No recommended alternative exists for pharyngeal infections in patients with cephalosporin allergies 2.
Test-of-Cure Requirements
Perform test-of-cure in:
- All pharyngeal gonorrhea cases 4
- All patients treated with alternative regimens 3
- One week after treatment using culture or NAAT 3
Treatment Failure Management
If treatment fails with the recommended regimen:
- Culture the specimen and perform antimicrobial susceptibility testing 3
- Consult infectious disease specialist or CDC (404-639-8659) 3
- Report to local/state health department within 24 hours 3
- Test all anatomic sites, especially pharynx (often asymptomatic but commonly involved in treatment failures) 5
- Treat sex partners from preceding 60 days 3
Emerging Therapies
Zoliflodacin (3 g oral single dose) showed 90.9% microbiological cure in Phase 3 trials versus 96.2% for ceftriaxone plus azithromycin, demonstrating non-inferiority for uncomplicated urogenital gonorrhea 6, 7. This represents the first new therapeutic class in nearly 2 decades and offers an oral alternative, particularly valuable for multidrug-resistant strains.
Key Clinical Pitfalls
- Don't use fluoroquinolones: No longer recommended due to widespread resistance 8, 3
- Don't use cefixime as first-line: Rising MICs and poor pharyngeal efficacy make this suboptimal 3
- Don't forget pharyngeal testing: Asymptomatic pharyngeal infections are common and harder to treat, facilitating resistance spread 5
- Don't skip partner treatment: Evaluate and treat all partners from preceding 60 days 3
Resistance Surveillance Context
The rationale for combination therapy evolved from concerns about cephalosporin resistance emergence. While azithromycin was initially added to delay resistance development, its own rising resistance led to the current recommendation favoring ceftriaxone monotherapy (with doxycycline only for chlamydia coverage) 1, 2. Maintaining culture capacity is essential for monitoring resistance trends, despite widespread NAAT use 3.