What is the recommended regimen for treating uncomplicated oropharyngeal gonorrhea, including dosing, co‑treatment for Chlamydia, alternatives for ceftriaxone allergy, pregnancy considerations, and follow‑up?

Treatment of Oropharyngeal Gonorrhea

For oropharyngeal gonorrhea, use ceftriaxone 500 mg IM as a single dose PLUS azithromycin 1 g orally as a single dose—this is the only reliably effective regimen for pharyngeal infections, with cure rates approaching 99%. 1, 2, 3

Why Pharyngeal Gonorrhea Requires Special Consideration

Pharyngeal gonorrhea is significantly more difficult to eradicate than urogenital or anorectal infections due to poor antibiotic penetration into tonsillar tissue, where nearly 90% of cephalosporins become protein-bound. 1, 2 This makes the choice of regimen critical—many alternatives that work well for genital infections fail at the pharynx.

Primary Recommended Regimen

Ceftriaxone 500 mg IM (single dose) PLUS azithromycin 1 g orally (single dose) 1, 2, 3, 4

• Ceftriaxone 500 mg provides superior bactericidal levels and achieves 99.1% cure rates for pharyngeal infections 1, 2, 4
• The 500 mg dose (rather than 250 mg) is particularly important for pharyngeal sites due to marked variability in cephalosporin clearance and half-life within tonsillar tissue 1
• Azithromycin 1 g addresses presumptive chlamydial co-infection (present in 40-50% of gonorrhea cases) and may help delay cephalosporin resistance 1, 2, 3

Alternative Regimens (When Ceftriaxone Unavailable)

Cefixime 400 mg orally (single dose) PLUS azithromycin 1 g orally (single dose) 1, 2, 3

• This oral alternative has inferior efficacy compared to ceftriaxone, with only 78.9% cure rate for pharyngeal infections (95% CI 54.5%-94%) 2
• Mandatory test-of-cure at 1 week is required due to documented treatment failures 1, 2
• Use culture for test-of-cure when possible (allows antimicrobial susceptibility testing); if NAAT is positive, confirm with culture 1, 2

Regimens to AVOID for Pharyngeal Gonorrhea

Spectinomycin

• Achieves only 52% cure rate for pharyngeal infections—completely inadequate 5, 1, 2
• Should never be used if pharyngeal exposure is suspected 1

Fluoroquinolones (Ciprofloxacin, Ofloxacin)

• Absolutely contraindicated due to widespread resistance, despite historical 99.8% cure rates 1, 2, 3
• Resistance patterns have rendered these agents ineffective 5

Azithromycin Monotherapy

• Single 1 g dose achieves only 93% efficacy for gonorrhea 1, 2
• Never use alone—risks rapid resistance emergence 1, 2

Gentamicin

• Has poor pharyngeal efficacy with only 20% cure rate in one study 1
• Most ceftriaxone treatment failures involve the pharynx, not urogenital sites 1

Special Populations

Pregnancy

Use ceftriaxone 500 mg IM (single dose) PLUS azithromycin 1 g orally (single dose) 5, 1, 2, 3

• Never use quinolones, tetracyclines, or doxycycline in pregnant or nursing women 5, 1
• If injection is refused, cefixime 400 mg orally PLUS azithromycin 1 g orally can be considered, but requires mandatory test-of-cure 2

Severe Cephalosporin Allergy

Azithromycin 2 g orally (single dose) 1, 2

• Has lower efficacy (only 93%) and high gastrointestinal side effects (35.3% of patients, with 2.9% severe) 1, 6
• Mandatory test-of-cure at 1 week is required 1, 2
• Alternative: Gentamicin 240 mg IM PLUS azithromycin 2 g orally, but note poor pharyngeal efficacy of gentamicin 1

Men Who Have Sex with Men (MSM)

• Ceftriaxone is the only recommended treatment due to higher prevalence of resistant strains 1, 2, 3
• Do not use quinolones in this population 2, 3
• Do not use patient-delivered partner therapy due to high risk of undiagnosed coexisting STDs or HIV 1, 3

Co-Treatment for Chlamydia

The dual therapy regimen (ceftriaxone PLUS azithromycin) addresses both infections simultaneously:

• Azithromycin 1 g orally provides single-dose chlamydia coverage 1, 2, 3
• If azithromycin cannot be used, doxycycline 100 mg orally twice daily for 7 days is required for chlamydia (but contraindicated in pregnancy) 1, 4
• Neither ceftriaxone nor cefixime alone eradicates concurrent chlamydial infection 7, 8

Follow-Up Requirements

Routine Test-of-Cure NOT Required

• Patients treated with recommended ceftriaxone-based regimens do NOT need routine test-of-cure unless symptoms persist 1, 2, 3

Mandatory Test-of-Cure Required For:

• Cefixime-based regimens (at 1 week) 1, 2, 3
• Azithromycin monotherapy (at 1 week) 1, 2
• Persistent symptoms after any treatment 1, 2, 3

Reinfection Screening

• Retest all patients at 3 months due to high reinfection risk (not to assess cure, but to detect reinfection) 1, 2, 3

Partner Management

All sexual partners from the preceding 60 days must be evaluated and treated with the same dual therapy regimen (ceftriaxone 500 mg IM PLUS azithromycin 1 g orally), regardless of symptoms or test results. 5, 1, 2, 3

• Expedited partner therapy with oral combination (cefixime 400 mg PLUS azithromycin 1 g) may be considered if partners cannot be linked to timely evaluation 1, 2, 3
• Patients must avoid sexual intercourse until therapy is completed and both patient and all partners are asymptomatic 5, 1, 2, 3

Treatment Failure Management

If symptoms persist after treatment:

1. Obtain specimens for culture with antimicrobial susceptibility testing immediately from all potentially infected sites 1, 2
2. Report to local public health officials within 24 hours 1, 3
3. Consult an infectious disease specialist 1, 2
4. Re-treat with salvage regimens:
   • Gentamicin 240 mg IM PLUS azithromycin 2 g orally (single dose), OR
   • Ertapenem 1 g IM for 3 days 1

Additional Screening at Time of Diagnosis

• Screen for syphilis with serology when gonorrhea is detected 5, 2, 3
• Co-test for HIV given that gonorrhea facilitates HIV transmission 2, 3

Critical Pitfalls to Avoid

• Never use spectinomycin for pharyngeal infections (only 52% cure rate) 5, 1, 2
• Never use fluoroquinolones due to widespread resistance 1, 2, 3
• Never use azithromycin 1 g alone for gonorrhea (only 93% efficacy) 1, 2
• Never use oral cephalosporins other than cefixime (cefuroxime, cefpodoxime) as they have not been effective against pharyngeal infections 5
• Never assume cefixime is equivalent to ceftriaxone—it has inferior pharmacokinetics and documented treatment failures 1, 2