Treatment of Gonorrhea
Primary Recommended Treatment
The recommended treatment for uncomplicated gonorrhea is ceftriaxone 500 mg intramuscularly as a single dose, plus azithromycin 1 g orally as a single dose. 1, 2
This dual therapy approach addresses both gonorrhea and potential chlamydial co-infection (present in 40-50% of cases), while also helping to prevent the emergence of cephalosporin resistance. 1
Rationale for Dual Therapy
- Combination therapy improves treatment efficacy and delays the emergence and spread of antimicrobial resistance by using two drugs with different mechanisms of action. 1
- Azithromycin is strongly preferred over doxycycline due to the convenience and compliance advantages of single-dose therapy, and substantially higher prevalence of gonococcal resistance to tetracycline than to azithromycin. 1
- If chlamydial infection has not been excluded by testing, concurrent treatment is mandatory. 2
Dosing Specifications
- Ceftriaxone 500 mg IM achieves a 99.1% cure rate for uncomplicated urogenital and anorectal gonorrhea. 1
- The 500 mg dose represents an update from the previous 250 mg recommendation, reflecting evolving resistance patterns. 2
- Azithromycin 1 g orally provides effective single-dose chlamydia coverage. 1
Alternative Regimens (When Ceftriaxone Unavailable)
If ceftriaxone is not available, use cefixime 400 mg orally as a single dose PLUS azithromycin 1 g orally as a single dose, with mandatory test-of-cure at 1 week. 1, 3
Critical Limitations of Cefixime
- Cefixime is significantly less effective than ceftriaxone, particularly for pharyngeal infections. 3
- Rising cefixime MICs have resulted in declining effectiveness for urogenital gonorrhea treatment. 1
- Oral cephalosporins are no longer first-line agents due to documented treatment failures in Europe. 4
- Test-of-cure is mandatory at 1 week when using cefixime. 1, 3
Severe Cephalosporin Allergy
For patients with severe cephalosporin allergy, use azithromycin 2 g orally as a single dose, with mandatory test-of-cure at 1 week. 1, 3
Important Caveats
- This regimen has lower efficacy (only 93% cure rate) compared to ceftriaxone-based therapy. 1, 5
- High gastrointestinal side effects occur with azithromycin 2 g (35.3% of patients experience GI symptoms, with 2.9% severe). 5
- Never use azithromycin 1 g alone for gonorrhea treatment—it is insufficient with only 93% efficacy. 1
Alternative for Severe Allergy
- Gentamicin 240 mg IM single dose PLUS azithromycin 2 g orally single dose achieved 100% cure rate in clinical trials. 1, 6
- However, gentamicin has poor pharyngeal efficacy (only 20% cure rate in one study). 1
Site-Specific Considerations
Pharyngeal Gonorrhea
Pharyngeal gonorrhea is significantly more difficult to eradicate than urogenital or anorectal infections, and ceftriaxone is the only reliably effective treatment. 1, 3
- Ceftriaxone has superior efficacy for pharyngeal infections compared to all alternative treatments. 1
- Spectinomycin has only 52% efficacy for pharyngeal infections and should be avoided. 1
- Most ceftriaxone treatment failures involve the pharynx, not urogenital sites. 1
Special Populations
Pregnant Women
Use ceftriaxone 500 mg IM plus azithromycin 1 g orally in pregnant women. 1, 3
- Never use quinolones or tetracyclines in pregnancy—they are absolutely contraindicated. 1, 3
- Doxycycline is contraindicated in pregnancy, nursing women, and children under 8 years. 1
Men Who Have Sex with Men (MSM)
Ceftriaxone is the only recommended treatment for MSM due to higher prevalence of resistant strains. 1, 3
- Never use quinolones for infections in MSM. 1
- Do not use patient-delivered partner therapy in MSM due to high risk of undiagnosed coexisting STDs or HIV. 1
Neonates
- Intravenous doses should be given over 60 minutes in neonates to reduce the risk of bilirubin encephalopathy. 7
- Ceftriaxone is contraindicated in premature neonates and in neonates ≤28 days requiring calcium-containing IV solutions. 7
Critical Pitfalls to Avoid
Fluoroquinolones Are Obsolete
Never use fluoroquinolones (ciprofloxacin, ofloxacin) for gonorrhea treatment due to widespread resistance. 1, 8
- Despite historical effectiveness (99.8% cure rate in 1998), quinolones are no longer recommended as of 2007. 4, 1
Monotherapy Is Insufficient
- Never use azithromycin 1 g alone—insufficient efficacy at only 93%. 1
- Never use ceftriaxone alone without addressing potential chlamydial co-infection. 1
Partner Management
All sex partners from the preceding 60 days must be evaluated and treated. 1, 3
- If the patient's last sexual contact was >60 days before symptom onset or diagnosis, treat the most recent partner. 3
- Partners should receive the same dual therapy regimen for both gonorrhea and chlamydia. 1
- Patients must avoid sexual intercourse until therapy is completed and both they and their partners are asymptomatic. 1
- Consider expedited partner therapy with oral combination therapy (cefixime 400 mg plus azithromycin 1 g) if partners cannot be linked to timely evaluation. 1, 3
Follow-Up and Test-of-Cure Requirements
Routine Follow-Up
- Patients treated with recommended ceftriaxone-based regimens do not need routine test-of-cure unless symptoms persist. 1
- Consider retesting all patients 3 months after treatment due to high risk of reinfection. 1
Mandatory Test-of-Cure Situations
Test-of-cure at 1 week is mandatory for:
- Patients receiving cefixime-based regimens 1, 3
- Patients receiving azithromycin monotherapy 1
- Patients with persistent symptoms after treatment 1
If Symptoms Persist
- Obtain culture with antimicrobial susceptibility testing immediately. 1, 3
- If nucleic acid amplification testing is positive at follow-up, confirm with culture. 1
- All positive cultures should undergo phenotypic antimicrobial susceptibility testing. 1
Treatment Failure Management
If treatment failure occurs, take immediate action:
- Obtain specimens for culture and antimicrobial susceptibility testing immediately. 1
- Report the case to local public health officials within 24 hours. 1
- Consult an infectious disease specialist. 1
Salvage Regimens for Treatment Failure
Recommended salvage regimens include: 1
- Gentamicin 240 mg IM PLUS azithromycin 2 g orally (single dose)
- Ertapenem 1 g IM for 3 days
- Spectinomycin 2 g IM PLUS azithromycin 2 g orally (avoid for pharyngeal infections)
Concurrent Testing Requirements
Screen for syphilis with serology at the time of gonorrhea diagnosis. 3