What is the recommended treatment for gonococcal urethritis?

Treatment of Gonococcal Urethritis

For uncomplicated gonococcal urethritis, administer ceftriaxone 500 mg intramuscularly as a single dose, plus doxycycline 100 mg orally twice daily for 7 days if chlamydial coinfection has not been excluded. 1

Primary Treatment Regimen

The current standard of care has evolved from dual therapy with azithromycin to a more targeted approach:

• Ceftriaxone 500 mg IM single dose is the first-line treatment for uncomplicated urogenital gonorrhea 1
• Add doxycycline 100 mg orally twice daily for 7 days if Chlamydia trachomatis coinfection has not been ruled out 1
• This represents an update from the previous 250 mg ceftriaxone dose, reflecting antimicrobial stewardship principles and rising azithromycin resistance 1

The shift away from routine dual therapy with azithromycin addresses concerns about antimicrobial stewardship and the increasing prevalence of azithromycin-resistant N. gonorrhoeae, while the increased ceftriaxone dose maintains high efficacy against evolving resistance patterns 1.

Alternative Regimens for Patients Unable to Receive Ceftriaxone

When ceftriaxone cannot be administered:

• Cefixime 400 mg orally single dose PLUS azithromycin 1 g orally single dose with mandatory test-of-cure in 1 week 2, 3
• This oral alternative is less effective than ceftriaxone due to declining cefixime susceptibility and rising minimum inhibitory concentrations 2, 4

For patients with severe cephalosporin allergy:

• Azithromycin 2 g orally as a single dose (not split) with mandatory test-of-cure in 1 week 2, 5

• This causes significant gastrointestinal distress but achieves approximately 96-99% cure rates 2, 5

• Never use azithromycin 1 g as monotherapy—it has only 93% efficacy and is inadequate 5

• Spectinomycin 2 g IM single dose is another alternative with 96.7% cure rate for urogenital infections, though availability is limited in many regions 2

Critical Management Components

Partner Management and Sexual Abstinence

• All sexual partners from the preceding 60 days must be evaluated and treated for both gonorrhea and chlamydia, regardless of symptoms 6, 2
• If the patient's last sexual contact was more than 60 days before symptom onset, treat the most recent partner 6
• Patients and all partners must abstain from sexual intercourse until therapy is completed and symptoms have resolved in both parties 6, 2
• Most apparent treatment failures result from reinfection by untreated partners, not true antimicrobial resistance 6

Test-of-Cure Requirements

• Routine test-of-cure is not necessary for patients treated with recommended ceftriaxone-based regimens who become asymptomatic 6
• Test-of-cure is mandatory when using alternative regimens (cefixime plus azithromycin, or azithromycin 2 g monotherapy) at 1 week post-treatment 2, 5
• Use culture or nucleic acid amplification test (NAAT) for test-of-cure; culture is preferred as it allows antimicrobial susceptibility testing 5

Special Populations

Pregnant Women

• Use the same ceftriaxone dose as non-pregnant patients (500 mg IM single dose) 2, 7
• Absolutely avoid quinolones and tetracyclines during pregnancy 6
• For cephalosporin-allergic pregnant patients, spectinomycin 2 g IM single dose is an option 6
• Treat presumptive chlamydial coinfection with erythromycin or amoxicillin, not doxycycline 6

HIV-Infected Patients

• Use identical treatment regimens as HIV-negative patients 2, 4
• Treatment is particularly vital because gonococcal urethritis increases HIV shedding and transmission risk 2, 4

Critical Pitfalls to Avoid

Quinolone Resistance

• Do not use quinolones (ciprofloxacin, levofloxacin, ofloxacin) as first-line therapy due to widespread resistance 2
• While older guidelines recommended quinolones, resistance rates have rendered them unreliable in most geographic areas 6

Inadequate Azithromycin Dosing

• Never use azithromycin 1 g as monotherapy—it cures only 93% of infections 5
• If azithromycin monotherapy is necessary (severe cephalosporin allergy), the dose must be 2 g, not split, despite gastrointestinal side effects 5

Partner Treatment Failures

• Skipping partner treatment is the primary cause of apparent treatment failure and perpetuates transmission 2
• Expedited partner therapy may be considered where legally permissible to ensure partners receive treatment 6

Management of Treatment Failure

If symptoms persist after recommended treatment:

• Obtain culture from urethral swab and perform antimicrobial susceptibility testing 6, 5
• Report treatment failures to public health authorities within 24 hours and consult infectious disease specialists 5
• Conduct test-of-cure 1 week after re-treatment 5
• Re-evaluate and re-treat all sexual partners from the preceding 60 days 5
• Consider persistent urethritis from other organisms (C. trachomatis, Trichomonas vaginalis, Mycoplasma genitalium) if gonorrhea is excluded 6