Treatment of Resistant Gonorrhea
For treatment failure after standard dual therapy with ceftriaxone 250-500 mg IM plus azithromycin 1 g, immediately treat with ceftriaxone 500 mg IM plus azithromycin 2 g orally as a single dose, obtain culture with antimicrobial susceptibility testing, consult infectious disease, and report to CDC within 24 hours. 1
Initial Management of Treatment Failure
When a patient presents with persistent gonorrhea infection after receiving the recommended combination therapy regimen:
- Obtain culture specimens immediately from all infected anatomic sites and perform phenotypic antimicrobial susceptibility testing using disk diffusion, Etest, or agar dilution 1
- Retain the isolate at the laboratory for possible further testing 1
- Report the case to CDC through local or state health department within 24 hours of diagnosis 1
- Consult an infectious disease specialist or STD/HIV Prevention Training Center immediately for treatment guidance 1, 2
Re-Treatment Regimen for Resistant Cases
The recommended re-treatment is ceftriaxone 500 mg IM plus azithromycin 2 g orally, both as single doses. 1, 3
This represents an escalation from standard therapy in two ways:
The rationale is that ceftriaxone remains the last highly effective antimicrobial for gonorrhea at all anatomic sites, and maintaining its effectiveness is critical 1
Mandatory Follow-Up Actions
- Conduct test-of-cure 1 week after re-treatment using culture (preferred) or NAAT if culture unavailable 1, 2
- Evaluate all sex partners from preceding 60 days promptly with culture and treat as indicated 1
- Ensure patient abstains from sexual intercourse until therapy completed and both patient and partners are asymptomatic 4, 5
Alternative Regimens for Cephalosporin Allergy
If the patient has severe cephalosporin allergy and cannot receive ceftriaxone:
- Use azithromycin 2 g orally as a single dose 1, 2
- Mandatory test-of-cure at 1 week is required with this alternative regimen 1, 2
- Consult infectious disease specialist as data are limited for alternative regimens 2
Important caveat: Azithromycin 2 g causes significant gastrointestinal distress in approximately 35% of patients, with moderate symptoms in 10% and severe in 3% 6
Critical Pitfalls to Avoid
- Never use quinolones (ciprofloxacin, ofloxacin) due to widespread resistance 4, 5
- Never use azithromycin 1 g as monotherapy - it has only 93% efficacy which is inadequate 4, 5
- Never use cefixime as first-line - CDC no longer recommends routine use due to rising MICs and limited efficacy for pharyngeal infections 1
- Never use spectinomycin for pharyngeal gonorrhea - it has only 52% efficacy at this site 4
- Never use gentamicin for pharyngeal infections - it has only 20% cure rate 4
Site-Specific Considerations for Resistant Cases
Pharyngeal gonorrhea is significantly more difficult to eradicate than urogenital or anorectal infections 4
For pharyngeal resistant cases:
- Ceftriaxone 500 mg IM is the only acceptable first-line agent 4
- Must be combined with azithromycin 1 g (or 2 g for treatment failure) 4
- Oral alternatives have unacceptably low cure rates at this site 4
Surveillance and Reporting Requirements
The capacity to perform culture is essential for monitoring antimicrobial resistance, yet it is declining due to widespread NAAT use 1
- Maintain access to laboratories that can perform culture and susceptibility testing 1
- All treatment failures must be reported to enable surveillance of emerging resistance patterns 1
- Continued monitoring is essential to ensure efficacy of recommended regimens 3
Partner Management in Resistant Cases
- All partners from preceding 60 days must be evaluated and treated with culture-based diagnosis when possible 1
- If partners cannot be linked to timely evaluation, expedited partner therapy may be considered using cefixime 400 mg plus azithromycin 1 g 1
- However, for confirmed resistant cases, partners should ideally receive the same escalated regimen as the index patient 1