What is the first-line treatment for an adult patient diagnosed with uncomplicated gonorrhea?

First-Line Treatment for Uncomplicated Gonorrhea

The first-line treatment for uncomplicated gonorrhea is ceftriaxone 250-500 mg intramuscularly PLUS azithromycin 1 g orally, both given as single doses on the same day, preferably simultaneously and under direct observation. 1, 2

Primary Treatment Regimen

• Ceftriaxone 250 mg IM (single dose) PLUS azithromycin 1 g orally (single dose) is the CDC-recommended regimen for uncomplicated urogenital, anorectal, and pharyngeal gonorrhea 3, 1

• The 500 mg dose of ceftriaxone is increasingly preferred over 250 mg due to evolving resistance patterns and is particularly important for pharyngeal infections 2

• Both medications should be administered together on the same day, preferably simultaneously and under direct observation 4, 5, 6, 7

Rationale for Dual Therapy

• Dual therapy addresses rising antibiotic resistance patterns and improves treatment efficacy while potentially delaying emergence and spread of cephalosporin resistance 1

• Azithromycin is strongly preferred over doxycycline as the second agent due to single-dose convenience, superior compliance, and substantially lower gonococcal resistance to azithromycin compared to tetracyclines 3, 1

• Co-infection with Chlamydia trachomatis occurs in 10-50% of gonorrhea cases, making dual therapy essential even when chlamydial testing is negative 1

Alternative Regimens (When Ceftriaxone Unavailable)

• If ceftriaxone is not available: Cefixime 400 mg orally (single dose) PLUS azithromycin 1 g orally (single dose), with mandatory test-of-cure at 1 week 3, 1

• If severe cephalosporin allergy: Azithromycin 2 g orally (single dose) with mandatory test-of-cure at 1 week, though this has lower efficacy (93%) and high gastrointestinal side effects 3, 1, 8

• Gentamicin 240 mg IM PLUS azithromycin 2 g orally is another alternative with 100% cure rate in trials, but has poor pharyngeal efficacy (only 20%) 1

Critical Site-Specific Considerations

• Pharyngeal gonorrhea is significantly more difficult to eradicate than urogenital or anorectal infections, making ceftriaxone the only reliably effective first-line agent 1, 2

• Ceftriaxone has superior efficacy for pharyngeal infections compared to all oral alternatives 1, 2

• Spectinomycin has only 52% efficacy for pharyngeal infections and should be avoided 1, 2

Medications to Never Use

• Never use fluoroquinolones (ciprofloxacin, ofloxacin) due to widespread resistance, despite historical cure rates of 99.8% 3, 1

• Never use azithromycin 1 g as monotherapy due to insufficient efficacy (only 93% cure rate) and risk of rapid resistance emergence 1, 2

• Cefixime is no longer recommended as first-line due to rising MICs and documented treatment failures in Europe 3, 1

Follow-Up Requirements

• Patients treated with the recommended ceftriaxone + azithromycin regimen do not need routine test-of-cure unless symptoms persist 1, 2, 4, 5

• Consider retesting all patients at 3 months due to high reinfection risk (not treatment failure) 1, 4, 5, 6, 7

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

Partner Management

• All sexual partners from the preceding 60 days must be evaluated and treated with the same dual therapy regimen, regardless of symptoms or test results 3, 1, 2

• 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 plus azithromycin 1 g) may be considered if partners cannot be linked to timely evaluation, but not for men who have sex with men (MSM) due to high risk of undiagnosed coexisting STDs or HIV 1

Special Population Considerations

• Pregnant women: Use the standard regimen (ceftriaxone + azithromycin 1 g); never use quinolones or tetracyclines in pregnancy 1, 2, 4, 5, 6, 7

• Men who have sex with men (MSM): Only use ceftriaxone-based regimens; never use quinolones due to higher prevalence of resistant strains 1

• Patients with recent foreign travel: Ceftriaxone is the only recommended treatment due to higher resistance rates internationally 1

Concurrent Testing and Treatment

• Screen for syphilis with serology at the time of gonorrhea diagnosis 1, 2

• Co-test for HIV given that gonorrhea facilitates HIV transmission 1

• Ceftriaxone has no activity against Chlamydia trachomatis, making the azithromycin component essential 9

Treatment Failure Management

• If treatment failure occurs, obtain culture specimens immediately from all infected sites and perform phenotypic antimicrobial susceptibility testing 3, 10

• Report the case to CDC through local or state health department within 24 hours 3, 10

• Consult an infectious disease specialist immediately 3, 10

• Re-treatment regimen: Ceftriaxone 500 mg IM PLUS azithromycin 2 g orally (both single doses), with test-of-cure at 1 week 10