What is the recommended treatment regimen for gonorrhea?

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Gonorrhea 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, which provides dual coverage for gonorrhea and presumptive chlamydial coinfection. 1, 2, 3

Primary Treatment Regimen

  • Ceftriaxone 500 mg IM (single dose) + Azithromycin 1 g orally (single dose) is the first-line therapy for uncomplicated gonococcal infections of the cervix, urethra, rectum, and pharynx. 1, 2, 3

  • This dual therapy achieves a 99.1% cure rate for urogenital and anorectal gonorrhea and addresses the 40-50% coinfection rate with chlamydia. 1, 2

  • The dose increase from 250 mg to 500 mg ceftriaxone reflects evolving antimicrobial stewardship concerns and resistance patterns. 3

Critical Rationale for Dual Therapy

  • Dual therapy with different mechanisms of action improves treatment efficacy and potentially delays emergence of cephalosporin resistance. 1

  • Azithromycin provides single-dose chlamydial coverage, eliminating the need for 7-day doxycycline in compliant patients. 1

  • If chlamydial infection has been excluded by testing, doxycycline 100 mg orally twice daily for 7 days may be substituted for azithromycin. 3

Alternative Regimens (When Ceftriaxone Unavailable)

  • Cefixime 400 mg orally (single dose) + Azithromycin 1 g orally (single dose) is the alternative regimen, but requires mandatory test-of-cure at 1 week due to inferior efficacy. 1, 2, 4

  • For severe cephalosporin allergy: Azithromycin 2 g orally as a single dose with mandatory test-of-cure at 1 week, though this has lower efficacy (93%) and high gastrointestinal side effects. 1, 5

  • Gentamicin 240 mg IM + Azithromycin 2 g orally (single dose) achieved 100% cure rates in clinical trials and represents an emerging alternative. 1, 6

Site-Specific Considerations

  • Pharyngeal gonorrhea is significantly more difficult to eradicate than urogenital or anorectal infections—ceftriaxone has superior efficacy and is the only reliably effective treatment for pharyngeal infections. 1, 2, 7

  • Spectinomycin has only 52% efficacy for pharyngeal infections and should never be used if pharyngeal exposure is suspected. 1, 2

  • Gentamicin has only 20% cure rate for pharyngeal infections. 1

Critical Pitfalls to Avoid

  • Never use fluoroquinolones (ciprofloxacin, ofloxacin) for gonorrhea treatment due to widespread resistance, despite their historical 99.8% cure rate. 1, 2, 8

  • Never use azithromycin 1 g alone for gonorrhea—it has only 93% efficacy, which is inadequate. 1, 2

  • Never use oral cephalosporins as first-line agents due to documented treatment failures in Europe. 1

  • Ceftriaxone should not be mixed with calcium-containing solutions due to precipitation risk. 9

Special Populations

Pregnancy

  • Use the standard regimen: Ceftriaxone 500 mg IM + Azithromycin 1 g orally. 1, 2

  • Never use quinolones, tetracyclines, or doxycycline in pregnancy. 1, 2

Men Who Have Sex with Men (MSM)

  • Only use ceftriaxone-based regimens—never quinolones—due to higher prevalence of resistant strains. 1, 2

  • Do not use patient-delivered partner therapy in MSM due to high risk of undiagnosed coexisting STDs or HIV. 1

Neonates

  • Ceftriaxone is contraindicated in premature neonates and those requiring calcium-containing IV solutions. 9

  • Administer IV doses over 60 minutes in neonates to reduce risk of bilirubin encephalopathy. 9

Follow-Up Requirements

  • Patients treated with the recommended ceftriaxone 500 mg + azithromycin 1 g regimen do NOT need routine test-of-cure unless symptoms persist. 1, 2, 7

  • Consider retesting all patients at 3 months after treatment due to high reinfection risk (not to assess cure, but to detect reinfection). 1, 2

  • If symptoms persist after treatment, obtain culture with antimicrobial susceptibility testing immediately. 1

Partner Management

  • All sexual partners from the preceding 60 days must be evaluated and treated with the same dual therapy regimen. 1, 2, 7

  • If last sexual contact was >60 days before diagnosis, treat the most recent partner. 7

  • Patients should avoid sexual intercourse until therapy is completed and both patient and partners are asymptomatic. 1, 2

  • Expedited partner therapy with oral combination therapy (cefixime 400 mg + azithromycin 1 g) may be considered if partners cannot be linked to timely evaluation. 1

Treatment Failure Management

  • If treatment failure occurs, 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

  • Recommended salvage regimens include: Gentamicin 240 mg IM + Azithromycin 2 g orally, Spectinomycin 2 g IM + Azithromycin 2 g orally, or Ertapenem 1 g IM for 3 days. 1

Concurrent Testing

  • Screen for syphilis with serology at the time of gonorrhea diagnosis. 1, 7

  • Perform HIV co-testing given that gonorrhea facilitates HIV transmission. 1, 3

References

Guideline

Gonorrhea Treatment Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Single-Dose Empiric Therapy for Gonorrhea and Chlamydia

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Update to CDC's Treatment Guidelines for Gonococcal Infection, 2020.

MMWR. Morbidity and mortality weekly report, 2020

Guideline

Treatment of Oral Gonorrhea with IM Ceftriaxone

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Diagnosis and management of gonococcal infections.

American family physician, 2012

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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