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, 3

This dual therapy regimen represents the current standard of care based on CDC guidelines and addresses both gonorrhea treatment and presumptive chlamydia coverage, given the 40-50% co-infection rate. 1, 2

Rationale for Dual Therapy

  • Dual therapy is essential due to 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 of cephalosporin resistance. 1

  • Azithromycin 1 g provides single-dose chlamydia coverage, eliminating the need for 7-day doxycycline therapy in compliant patients. 2

  • Critical caveat: Azithromycin 1 g alone is insufficient for gonorrhea treatment, with only 93% efficacy, and should never be used as monotherapy. 1, 4

Alternative Regimens (When Ceftriaxone Unavailable)

Oral Alternative

  • Cefixime 400 mg orally single dose PLUS azithromycin 1 g orally single dose can be used if ceftriaxone is unavailable. 1, 5

  • Mandatory test-of-cure at 1 week is required with this regimen due to inferior efficacy compared to ceftriaxone, particularly for pharyngeal infections. 1, 5

  • Cefixime achieves similar cure rates for urogenital infections (96-98%) but is significantly less effective for pharyngeal gonorrhea. 6

Severe Cephalosporin Allergy

  • Azithromycin 2 g orally single dose is recommended for patients with severe cephalosporin allergy. 1, 5

  • This regimen has lower efficacy (93%) and high gastrointestinal side effects (35% of patients experience GI symptoms, with 2.9% severe). 1, 4

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

  • Gentamicin 240 mg intramuscularly PLUS azithromycin 2 g orally is an alternative with 100% cure rate in clinical trials, but has poor pharyngeal efficacy (only 80% cure rate). 1, 7, 8

Site-Specific Considerations

Pharyngeal Gonorrhea

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

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

  • Gentamicin has only 80% cure rate for pharyngeal infections compared to 96% for ceftriaxone. 7

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

Urogenital and Rectal Infections

  • Ceftriaxone achieves 99.1% cure rate for uncomplicated urogenital and anorectal gonorrhea. 1

  • Gentamicin achieves 94% cure rate for genital infections and 90% for rectal infections, making it potentially useful for isolated genital infection in cephalosporin-allergic patients. 7

Special Populations

Pregnancy

  • Use ceftriaxone 500 mg intramuscularly single dose PLUS azithromycin 1 g orally single dose. 1, 2, 5

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

  • Ceftriaxone is the preferred cephalosporin in pregnancy. 1

Men Who Have Sex with Men (MSM)

  • Ceftriaxone is the only recommended treatment for MSM due to higher prevalence of resistant strains. 1, 5

  • Quinolones are contraindicated in this population. 1, 5

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

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

  • Never use azithromycin 1 g alone for gonorrhea treatment due to insufficient 93% efficacy. 1, 2

  • Never substitute tablets or capsules for suspension in treating otitis media, as suspension results in higher peak blood levels. 9

  • Do not use diluents containing calcium (Ringer's solution, Hartmann's solution) with ceftriaxone, as precipitation can occur. 10

  • In neonates, administer ceftriaxone intravenously over 60 minutes to reduce risk of bilirubin encephalopathy. 10

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

  • Consider retesting all patients 3 months after treatment due to high risk of reinfection (not treatment failure). 1, 2

Mandatory Test-of-Cure (1 Week)

  • Required for patients receiving cefixime-based regimens. 1, 5

  • Required for patients receiving azithromycin 2 g monotherapy. 1, 5

  • Required for patients with persistent symptoms after treatment. 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 intramuscularly PLUS azithromycin 2 g orally, or ertapenem 1 g intramuscularly for 3 days. 1

  • If nucleic acid amplification testing is positive at follow-up, confirm with culture, and all positive cultures should undergo phenotypic antimicrobial susceptibility testing. 1

Partner Management

  • All sexual partners from the preceding 60 days should be evaluated and treated with the same dual therapy regimen. 1, 2, 5

  • If the patient's last sexual contact was >60 days before symptom onset or diagnosis, treat the most recent partner. 5

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

  • Consider expedited partner therapy with oral combination therapy (cefixime 400 mg plus azithromycin 1 g) if partners cannot be linked to timely evaluation. 1

Concurrent Testing

  • Screen for syphilis with serology at the time of gonorrhea diagnosis. 5

  • Test for HIV and other sexually transmitted infections as clinically indicated. 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

Research

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

MMWR. Morbidity and mortality weekly report, 2020

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

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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