What is the recommended oral regimen for uncomplicated gonorrhea?

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Last updated: October 27, 2025View editorial policy

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Recommended Oral Regimen for Uncomplicated Gonorrhea

For uncomplicated gonorrhea, the recommended oral regimen is cefixime 400 mg orally in a single dose PLUS azithromycin 1 g orally in a single dose, with a test-of-cure performed 1 week after treatment. 1, 2

Primary Treatment Recommendations

  • The first-line treatment for uncomplicated gonorrhea is ceftriaxone 250 mg IM in a single dose PLUS azithromycin 1 g orally in a single dose 1, 2
  • When an oral regimen is required, cefixime 400 mg orally in a single dose PLUS azithromycin 1 g orally in a single dose is recommended 1, 2
  • Azithromycin is preferred over doxycycline due to convenience and compliance advantages of single-dose therapy, and substantially higher prevalence of gonococcal resistance to tetracycline 1
  • A test-of-cure should be performed 1 week after treatment with oral regimens 1, 2

Alternative Oral Regimens for Special Circumstances

  • For patients with severe cephalosporin allergy, azithromycin 2 g orally in a single dose is recommended, with a test-of-cure performed 1 week after treatment 1, 2, 3
  • This alternative regimen has been shown to be effective but may cause significant gastrointestinal distress 1, 4

Rationale for Dual Therapy

  • Dual therapy with two antimicrobials with different mechanisms of action is recommended to improve treatment efficacy and potentially delay emergence of cephalosporin resistance 2
  • The combination addresses possible chlamydial co-infection, which is common in patients with gonorrhea 2, 3

Site-Specific Considerations

  • Pharyngeal gonorrhea is more difficult to eradicate than urogenital or anorectal infections 1, 2
  • Ceftriaxone has superior efficacy for pharyngeal infections compared to oral alternatives 2
  • Cefixime has shown efficacy of 96.5% for urogenital and rectal infections, but only 78.9% for pharyngeal infections 1

Important Clinical Considerations

  • Azithromycin 1 g alone is insufficient for gonorrhea treatment, with only 93% efficacy 1, 2
  • Quinolones (ciprofloxacin, ofloxacin) are no longer recommended due to widespread resistance 1, 2
  • Cefixime 400 mg has demonstrated efficacy comparable to ceftriaxone in clinical trials (96-98% cure rates) for urogenital and rectal infections 5, 6
  • FDA has approved cefixime for treatment of uncomplicated gonorrhea 7

Partner Management

  • All sex partners from the preceding 60 days should be evaluated and treated 1, 2
  • Patients should avoid sexual intercourse until therapy is completed and both they and their partners are asymptomatic 2

Follow-Up Recommendations

  • For patients treated with oral regimens, a test-of-cure should be performed 1 week after treatment 1, 2
  • The test-of-cure should ideally be performed with culture or with a NAAT if culture is not readily available 1
  • Consider retesting all patients 3 months after treatment due to high risk of reinfection 2

Treatment Failure Management

  • For suspected treatment failures, obtain specimen for culture and antimicrobial susceptibility testing 1, 2
  • Consult an infectious disease specialist for guidance on alternative treatment options 2, 3
  • Report the case to local public health officials within 24 hours 2, 3

References

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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