Gonorrhea Treatment
For uncomplicated gonorrhea, treat with ceftriaxone 500 mg IM as a single dose (increase to 1 g IM if body weight ≥150 kg), plus azithromycin 1 g orally as a single dose if chlamydial coinfection has not been excluded. This dual therapy approach maximizes treatment efficacy while addressing common coinfection and potentially delaying resistance emergence 1.
Standard Treatment Regimen
Urogenital, Anorectal, and Pharyngeal Gonorrhea
The recommended first-line treatment consists of:
- Ceftriaxone 500 mg IM as a single dose 2, 3
- Plus azithromycin 1 g orally as a single dose (preferred over doxycycline due to single-dose convenience and lower tetracycline resistance rates) 1
For patients weighing ≥150 kg: Increase ceftriaxone dose to 1 g IM as a single dose 4, 3. This weight-based adjustment ensures adequate drug exposure in larger patients, though clinical data supporting specific dosing above 500 mg remain limited 1.
The 2020 CDC update increased the standard ceftriaxone dose from 250 mg to 500 mg based on antimicrobial stewardship principles and evolving resistance patterns, while removing azithromycin as a mandatory component when chlamydial infection is excluded 2, 3. However, dual therapy remains preferred when chlamydia status is unknown.
Alternative if Ceftriaxone Unavailable
If ceftriaxone is not readily available:
- Cefixime 400 mg orally as a single dose
- Plus azithromycin 1 g orally as a single dose
- Mandatory test-of-cure in 1 week 1
Critical caveat: Cefixime provides lower and less sustained bactericidal levels than ceftriaxone and has limited efficacy for pharyngeal infections 1. Rising cefixime MICs make this a suboptimal choice that should only be used when ceftriaxone is truly unavailable.
Special Populations and Circumstances
Severe Cephalosporin Allergy
For patients with documented severe cephalosporin allergy:
- Gentamicin 240 mg IM as a single dose
- Plus azithromycin 2 g orally as a single dose
- Mandatory test-of-cure in 1 week 5, 6, 3
Alternative option:
- Gemifloxacin 320 mg orally plus azithromycin 2 g orally as single doses 6
Important limitations: Both gentamicin and spectinomycin have poor efficacy against pharyngeal gonorrhea 5. One study was stopped early because only 2 of 10 pharyngeal infections treated with gentamicin were cured. For suspected pharyngeal infection in cephalosporin-allergic patients, consult an infectious disease specialist immediately 1, 5.
The evidence for these alternative regimens comes from a well-designed randomized trial showing 100% cure rate for urogenital infections with gentamicin/azithromycin and 99.5% with gemifloxacin/azithromycin 6. However, gastrointestinal adverse events were common with both regimens, particularly with the 2 g azithromycin dose.
Pharyngeal Gonorrhea
Pharyngeal infections are more difficult to eradicate than urogenital or anorectal sites 1, 7. Use the same standard regimen:
- Ceftriaxone 500 mg IM (or 1 g if ≥150 kg)
- Plus azithromycin 1 g orally 1
Do not use oral cephalosporins for pharyngeal infections - cefixime demonstrates limited efficacy at this site 1. A retrospective study showed that oral cephalosporin plus doxycycline had a 33% repeat positive test rate for pharyngeal gonorrhea, compared to only 7% with oral cephalosporin plus azithromycin 8.
The pharynx is particularly concerning because:
- It serves as a reservoir for transmission through kissing and oral-genital contact 5
- It's a key site for antimicrobial resistance emergence through DNA exchange with commensal Neisseria species 5
- Infections are typically asymptomatic and can persist up to 16 weeks 5
Pregnancy
Pregnant women should receive the same standard regimen as non-pregnant adults 1, 9:
- Ceftriaxone 500 mg IM (or 1 g if ≥150 kg)
- Plus azithromycin 1 g orally
Contraindications in pregnancy:
For cephalosporin-allergic pregnant patients, options are extremely limited. Spectinomycin 2 g IM was historically used but is no longer available in the United States 7. Consult infectious disease specialist immediately.
Test-of-Cure and Follow-Up
Test-of-cure is NOT routinely recommended for patients treated with the standard ceftriaxone-based regimen 1, 7, 3.
Test-of-cure IS mandatory for:
- Alternative regimens (cefixime-based, gentamicin-based, or azithromycin monotherapy) 1
- Severe cephalosporin allergy cases 1
- Pharyngeal infections treated with non-standard regimens 7
Perform test-of-cure 1 week after treatment using culture (preferred) or NAAT if culture unavailable 1. If NAAT is positive, confirm with culture and perform antimicrobial susceptibility testing 1.
Retesting for reinfection: All patients should be retested 3 months after treatment regardless of regimen used, as reinfection rates are high 9, 3. Pregnant women with antenatal gonococcal infection should be retested in the third trimester 9.
Treatment Failure Management
If a patient has persistent symptoms or positive test after standard treatment:
Obtain culture and antimicrobial susceptibility testing (mandatory) 1
Report to local/state health department within 24 hours 1
Consult infectious disease specialist 1
Consider re-treatment with:
Evaluate and treat all sex partners from preceding 60 days 1
Critical Pitfalls to Avoid
- Never use azithromycin 2 g as monotherapy for routine treatment due to rapid resistance emergence 1, 3
- Never use oral cephalosporins as first-line - they are inferior to ceftriaxone 1, 3
- Never use quinolones - widespread resistance makes them obsolete 3
- Never assume pharyngeal infection will respond to regimens effective for urogenital sites - always use ceftriaxone-based therapy 5, 8
- Never skip partner treatment - all partners from preceding 60 days must be evaluated and treated 1
- Never use calcium-containing diluents with ceftriaxone due to precipitation risk 10