What is the recommended treatment regimen for gonorrhea?

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Gonorrhea Treatment

Primary Recommendation

For uncomplicated gonorrhea of the cervix, urethra, rectum, or pharynx, treat with ceftriaxone 500 mg intramuscularly as a single dose PLUS azithromycin 1 g orally as a single dose. 1, 2

This dual therapy regimen addresses both gonorrhea and presumptive chlamydial co-infection, which occurs in 40-50% of gonorrhea cases. 1, 2


Rationale for Dual Therapy

  • Dual therapy is essential because of rising antibiotic resistance patterns and the extremely high co-infection rate with chlamydia (40-50% of gonorrhea patients). 1, 2

  • The combination improves treatment efficacy and potentially delays emergence and spread of cephalosporin resistance. 1

  • Azithromycin is preferred over doxycycline for chlamydia coverage due to the convenience and compliance advantages of single-dose therapy, and substantially higher prevalence of gonococcal resistance to tetracycline than to azithromycin. 1


Alternative Regimens (When Ceftriaxone Unavailable)

Second-Line Option

  • Cefixime 400 mg orally single dose PLUS azithromycin 1 g orally single dose can be used if ceftriaxone is unavailable. 1, 3

  • Critical caveat: This regimen is less effective than ceftriaxone, particularly for pharyngeal infections, and requires mandatory test-of-cure at 1 week. 1, 3

  • Rising cefixime MICs have resulted in declining effectiveness for urogenital gonorrhea treatment. 1

Severe Cephalosporin Allergy

  • Azithromycin 2 g orally single dose is recommended for patients with severe cephalosporin allergy. 1, 3

  • This regimen has lower efficacy (only 93% cure rate) and high gastrointestinal side effects. 1

  • Mandatory test-of-cure at 1 week is required. 1

  • Alternative: Gentamicin 240 mg intramuscularly PLUS azithromycin 2 g orally achieved 100% cure rate in clinical trials, but has poor pharyngeal efficacy (only 20% cure rate). 1, 4


Site-Specific Considerations

Pharyngeal Gonorrhea

  • Pharyngeal gonorrhea is significantly more difficult to eradicate than urogenital or anorectal infections. 1, 2

  • Ceftriaxone has superior efficacy for pharyngeal infections compared to all alternative treatments and is strongly preferred. 1, 2

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

  • Gentamicin also has poor pharyngeal efficacy (only 20% cure rate in one study). 1

  • Most cases of ceftriaxone treatment failure involve the pharynx, not urogenital sites. 1


Special Populations

Pregnant Women

  • Use ceftriaxone 500 mg intramuscularly single dose PLUS azithromycin 1 g orally single dose. 1, 2

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

  • Ceftriaxone is the preferred cephalosporin. 1

Men Who Have Sex with Men (MSM)

  • Ceftriaxone is the only recommended treatment for MSM due to higher prevalence of resistant strains. 1, 3

  • Quinolones should never be used in MSM. 1, 3

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

Patients with Recent Foreign Travel

  • Ceftriaxone is the only recommended treatment for patients with history of recent foreign travel due to higher likelihood of resistant strains. 1

Critical Pitfalls to Avoid

  • Never use quinolones (ciprofloxacin, ofloxacin) for gonorrhea treatment due to widespread resistance, despite their historical 99.8% cure rates. 1, 2, 5

  • Never use azithromycin 1 g alone for gonorrhea treatment due to insufficient efficacy (only 93% cure rate). 1, 2

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

  • Ceftriaxone must not be administered simultaneously with calcium-containing IV solutions in any patient, and must never be used in neonates ≤28 days requiring calcium-containing IV solutions due to risk of fatal ceftriaxone-calcium precipitation. 6


Follow-Up Requirements

Routine Follow-Up

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

  • All patients should be retested approximately 3 months after treatment due to high reinfection risk. 1, 2

Mandatory Test-of-Cure (1 Week Post-Treatment)

  • Required for patients receiving cefixime-based regimens. 1, 3

  • Required for patients receiving azithromycin 2 g monotherapy. 1, 3

  • Required for patients receiving gentamicin-based regimens. 1

Persistent Symptoms

  • If symptoms persist after treatment, obtain culture with antimicrobial susceptibility testing immediately. 1, 3

  • If nucleic acid amplification testing is positive at follow-up, confirm with culture, and all positive cultures should undergo phenotypic antimicrobial susceptibility testing. 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

Salvage Regimens for Suspected Ceftriaxone Failure

  • Gentamicin 240 mg intramuscularly PLUS azithromycin 2 g orally (single dose). 1

  • Spectinomycin 2 g intramuscularly PLUS azithromycin 2 g orally (single dose). 1

  • Ertapenem 1 g intramuscularly for 3 days. 1


Partner Management

  • All sexual partners from the preceding 60 days should be evaluated and treated with the same dual therapy regimen. 1, 2, 3

  • If the patient's last sexual contact was >60 days before symptom onset or diagnosis, treat the most recent partner. 3

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

  • If partners' treatment cannot be ensured, consider expedited partner therapy with oral combination therapy (cefixime 400 mg plus azithromycin 1 g). 1


Concurrent Testing Requirements

  • Screen for syphilis with serology at the time of gonorrhea diagnosis. 1, 3

  • Co-testing for HIV should also be performed given the facilitation of HIV transmission by gonorrhea. 1

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

Guideline

Gonorrhea Treatment Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

The efficacy and safety of gentamicin plus azithromycin and gemifloxacin plus azithromycin as treatment of uncomplicated gonorrhea.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2014

Research

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

MMWR. Morbidity and mortality weekly report, 2020

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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