Oral Cephalosporin Treatment for Gonorrhea
Current Recommendation
Oral cephalosporins are no longer recommended as first-line therapy for gonorrhea due to emerging resistance patterns; ceftriaxone 250 mg intramuscularly combined with azithromycin 1 g orally is the only reliably effective regimen. 1
Historical Context and Resistance Evolution
Cefixime 400 mg orally was previously a CDC-recommended first-line oral option, achieving 97.4% cure rates for uncomplicated urogenital and anorectal gonorrhea 2, 3. However, between 2006-2011, minimum inhibitory concentrations (MICs) for cefixime increased progressively, with 0.2% of isolates showing decreased susceptibility (MIC ≥0.5 μg/mL) by 2010 1. This prompted CDC to remove cefixime from first-line recommendations in 2012 1.
Current Treatment Algorithm
First-Line Therapy (All Sites)
- Ceftriaxone 250 mg IM (single dose) PLUS azithromycin 1 g orally (single dose) 1
- This combination addresses both gonorrhea and concurrent Chlamydia trachomatis infection (present in ≥50% of cases) 3
- Dual therapy also provides protection against emerging cephalosporin resistance 1
If Cefixime Must Be Used (Not Recommended)
If ceftriaxone is absolutely unavailable and local resistance data supports use:
- Cefixime 400 mg orally (single dose) PLUS azithromycin 1 g orally (single dose) 1, 4
- Mandatory test-of-cure at 1 week at the site of infection 1
- This regimen is particularly unreliable for pharyngeal gonorrhea (only 91% efficacy vs. 98% for ceftriaxone) 2
Cephalosporin Allergy
- Spectinomycin 2 g IM (single dose) for urogenital/anorectal sites 1
- Critical limitation: Only 52% effective against pharyngeal gonorrhea 1
- Spectinomycin is currently unavailable in many regions 1
Site-Specific Considerations
Pharyngeal Gonorrhea
- Most difficult site to eradicate—requires regimens with >90% cure rates 1
- Ceftriaxone 250 mg IM achieves 99.1% cure rates 2
- Cefixime achieves only 91% cure rates 2
- Oral cephalosporins other than cefixime (cefuroxime axetil, cefpodoxime) show unacceptably low pharyngeal cure rates (56.9-78.9%) 1
Urogenital/Anorectal Sites
- Ceftriaxone remains superior with 99.1% efficacy 2
- Historical cefixime data showed 96-98% efficacy, but this predates current resistance patterns 3, 5
Alternative Oral Cephalosporins (Not Recommended)
Cefpodoxime Proxetil
- 200 mg orally: 96.5% cure rate for urogenital/rectal sites (95% CI: 94.8-98.9%) 1
- Does not meet minimum efficacy criteria (lower CI boundary <95%) 1
- Pharyngeal efficacy unacceptable at 78.9% 1
Cefuroxime Axetil
- 1 g orally: 95.9% cure rate for urogenital/rectal sites (95% CI: 94.5-97.3%) 1
- Does not meet minimum efficacy criteria 1
- Pharyngeal efficacy unacceptable at 56.9% 1
Critical Pitfalls to Avoid
Resistance Patterns
- Never use quinolones (ciprofloxacin, ofloxacin) for gonorrhea—widespread resistance eliminated this class in 2007 1
- Local resistance data is essential; empiric oral cephalosporin use is inappropriate without current susceptibility patterns 1
Pharmacokinetic Limitations
- Cefixime 400 mg provides lower and less sustained bactericidal levels than ceftriaxone 125 mg IM 1, 2
- Oral cephalosporins achieve poor prostatic tissue penetration and should never be used for gonococcal prostatitis 6
Coinfection Management
- Always treat for concurrent chlamydia unless NAAT is negative 1
- Chlamydia persists in ≥50% of co-infected patients after gonorrhea treatment alone 3
Test-of-Cure Requirements
- Not required for patients treated with recommended ceftriaxone-based regimens 1
- Mandatory at 1 week if cefixime or other alternative regimens are used 1
- Persistent symptoms after treatment usually indicate reinfection, not treatment failure 1
Special Populations
Pregnancy
- Ceftriaxone 250 mg IM is safe and preferred 1
- Quinolones and tetracyclines are contraindicated 1
- Treat concurrent chlamydia with azithromycin 1 g orally (preferred) or amoxicillin 1
HIV Infection
- Use identical regimens as HIV-negative patients 1