What is the cure rate for cefixime (Cephalosporin) in treating gonorrhea?

Cefixime Cure Rate for Gonorrhea

Cefixime 400 mg orally achieves a 97.4% cure rate for uncomplicated urogenital and anorectal gonorrhea, but is no longer recommended as first-line therapy due to rising resistance patterns and inferior pharmacokinetics compared to ceftriaxone. 1, 2

Historical Efficacy Data

• Clinical trials demonstrated that cefixime 400 mg cured 97.4% of uncomplicated urogenital and anorectal gonococcal infections, meeting the minimum 95% efficacy threshold for first-line therapy 1, 2
• Individual studies showed comparable results: 96% cure rate (400 mg dose) and 98% cure rate (800 mg dose) in head-to-head comparisons with ceftriaxone 3
• For pharyngeal gonorrhea specifically, cefixime demonstrates only 91% efficacy, which is substantially lower than urogenital sites and represents a critical limitation 2
• A study from Kenya showed 98% cure rate (118 of 121 patients) for uncomplicated urethritis and cervicitis 4

Why Cefixime Is No Longer First-Line

The CDC removed cefixime from first-line recommendations in 2012 due to concerning resistance trends that mirror the pattern seen with fluoroquinolones in the 1990s. 1, 5

Rising Resistance Patterns

• Isolates with elevated cefixime MICs (≥0.25 μg/mL) increased from 0.1% in 2006 to 1.5% in 2011 nationally, with the West region showing an increase from 0.2% to 3.2% 1
• Among men who have sex with men (MSM), elevated cefixime MICs increased from 0.2% to 3.8% between 2006 and 2011 1, 5
• Geographic hotspots emerged: Honolulu (0% to 17.0%), Minneapolis (0% to 6.9%), Portland (0% to 6.5%), and San Diego (0% to 6.4%) 1
• This geographic and demographic pattern (West region, MSM population) exactly replicated fluoroquinolone resistance emergence before it spread nationwide 1

Pharmacodynamic Inferiority

• Cefixime 400 mg does not provide bactericidal blood levels as high or sustained as ceftriaxone 125 mg IM, maintaining free drug concentrations above MIC90 for only 22-50 hours compared to ceftriaxone's superior profile 1, 2, 6
• The oral formulation achieves lower peak concentrations, which is particularly problematic for pharyngeal infections where tissue penetration is critical 1

Risk of Accelerating Ceftriaxone Resistance

• Continued cefixime use may hasten development of resistance to ceftriaxone, the last remaining highly effective single-dose treatment for gonorrhea at all anatomic sites 1, 5
• Preserving ceftriaxone effectiveness is a critical public health priority given the lack of alternative agents 1, 5

Current Treatment Recommendations

Cefixime 400 mg plus azithromycin 1 g orally is now relegated to alternative therapy only when ceftriaxone is unavailable, and requires mandatory test-of-cure at 1 week. 1, 7

When Cefixime May Still Be Used

• Only as alternative therapy when ceftriaxone is not available or feasible 1, 7
• Must be combined with azithromycin 1 g orally (preferred over doxycycline due to single-dose convenience and lower gonococcal resistance rates) 1
• Test-of-cure is mandatory 1 week after treatment to detect treatment failures 1, 7

Populations Where Cefixime Should Be Avoided

• Never use cefixime as first-line for MSM due to higher prevalence of resistant strains in this population 7
• Avoid for pharyngeal infections given 91% efficacy versus >95% required for first-line therapy 2
• A 2022 study confirmed ceftriaxone 1 g IV plus doxycycline was superior to cefixime 800 mg plus doxycycline for gonorrhea-chlamydia co-infection (odds ratio 4.41) 8

Critical Caveats and Pitfalls

• Cefixime does not treat concurrent chlamydial infection, which persists in at least 50% of co-infected patients, requiring mandatory co-treatment with azithromycin or doxycycline 2, 3
• These cure rates apply only to uncomplicated infections; disseminated gonococcal infection requires parenteral ceftriaxone 2
• The 97.4% cure rate data predates current resistance patterns and likely overestimates contemporary effectiveness 1, 2
• Never use cefixime alone without azithromycin or doxycycline co-treatment 1, 7
• Lower doses (200 mg) showed 95% efficacy but should never be used clinically as they risk selecting resistant strains 9