Gonorrhea Treatment
Primary Recommendation
For uncomplicated gonorrhea of the cervix, urethra, rectum, or pharynx, treat with ceftriaxone 500 mg IM as a single dose PLUS doxycycline 100 mg orally twice daily for 7 days (if chlamydial coinfection has not been excluded). 1
This represents the most current CDC guidance from 2020, which updated the previous dual therapy recommendation. The shift from mandatory azithromycin to conditional doxycycline reflects antimicrobial stewardship concerns and rising azithromycin resistance patterns. 1
Rationale for Current Regimen
Ceftriaxone dose increased from 250 mg to 500 mg based on evolving resistance patterns and the need for higher tissue concentrations, particularly for pharyngeal infections. 1
Azithromycin is no longer routinely recommended as the second agent due to increasing resistance and antimicrobial stewardship concerns about its impact on commensal organisms. 1
Doxycycline is now the preferred companion drug when chlamydial coinfection has not been excluded, given that 40-50% of gonorrhea patients have concurrent chlamydia. 2
If chlamydia has been definitively ruled out by testing, ceftriaxone monotherapy is acceptable. 1
Alternative Regimens When Ceftriaxone Unavailable
If ceftriaxone is not available, use cefixime 400 mg orally once PLUS azithromycin 1 g orally once, with mandatory test-of-cure at 1 week. 2, 3, 4
Cefixime is significantly less effective than ceftriaxone, particularly for pharyngeal infections (approximately 10% lower cure rate). 2, 3
Rising cefixime MICs have resulted in declining effectiveness for urogenital gonorrhea. 2
Never substitute cefixime for ceftriaxone in pharyngeal infections - ceftriaxone has superior efficacy at this site. 2
Severe Cephalosporin Allergy
For patients with severe cephalosporin allergy, use azithromycin 2 g orally once, with mandatory test-of-cure at 1 week. 2, 3
This regimen has lower efficacy and higher gastrointestinal side effects. 5
Spectinomycin 2 g IM is an alternative but has poor efficacy (only 52%) against pharyngeal gonorrhea. 2
Gentamicin 240 mg IM is NOT recommended as first-line therapy - a 2019 randomized trial showed it was inferior to ceftriaxone (91% vs 98% clearance overall, and only 80% vs 96% for pharyngeal infections). 6
Site-Specific Considerations
Pharyngeal gonorrhea is significantly more difficult to eradicate than urogenital or anorectal infections. 5, 2
Ceftriaxone 500 mg IM is the only reliably effective treatment for pharyngeal infections. 2
For uncomplicated urogenital gonorrhea alone, ceftriaxone 250 mg IM remains effective, but the 500 mg dose is now standard across all sites for simplicity. 7, 1
Special Populations
Men Who Have Sex with Men (MSM)
Use only ceftriaxone 500 mg IM - this population has higher prevalence of resistant strains. 2, 3
Never use quinolones in MSM due to widespread resistance. 2, 3
Pregnant Women
Ceftriaxone is the preferred treatment - quinolones and tetracyclines are contraindicated. 2, 3
Use azithromycin 1 g orally once instead of doxycycline for presumptive chlamydia treatment. 2
Patients with Recent Foreign Travel
- Use only ceftriaxone 500 mg IM due to higher likelihood of resistant strains. 2
Neonates
Ceftriaxone is contraindicated in neonates ≤28 days if they require calcium-containing IV solutions due to precipitation risk. 7
For neonates who can receive ceftriaxone, administer IV doses over 60 minutes to reduce risk of bilirubin encephalopathy. 7
Critical Pitfalls to Avoid
Never use fluoroquinolones (ciprofloxacin, ofloxacin) for gonorrhea treatment - widespread resistance makes them obsolete despite their historical effectiveness (99.8% cure rate in 1998). 5, 2, 1
Never use azithromycin 1 g alone - it has insufficient efficacy (only 93% cure rate). 5, 2
Never mix ceftriaxone with calcium-containing solutions (Ringer's, Hartmann's) due to precipitation risk. 7
Do not substitute oral cefixime for IM ceftriaxone in pharyngeal infections - significantly lower efficacy. 2
Partner Management
Evaluate and treat all sex partners from the preceding 60 days. 2, 3
If the patient's last sexual contact was >60 days before symptom onset or diagnosis, treat the most recent partner. 3
Patients should avoid sexual intercourse until therapy is completed and both partners are asymptomatic. 2
Consider expedited partner therapy if partners' treatment cannot be ensured. 2
Follow-Up and Testing
Patients treated with recommended regimens do not need routine test-of-cure unless symptoms persist. 5, 2
Mandatory test-of-cure at 1 week for patients receiving cefixime or azithromycin monotherapy. 2, 3
Retest all patients at 3 months due to high reinfection rates (approximately 10% within 2 years). 2, 8
Patients with persistent symptoms should have culture with antimicrobial susceptibility testing. 5, 2
Screen for syphilis with serology at the time of gonorrhea diagnosis. 3
Test for other sexually transmitted infections including HIV and chlamydia. 9