What are the recommended ceftriaxone dosing regimens for uncomplicated gonorrhea, disseminated gonococcal infection, and syphilis in adults, including adjustments for patients weighing ≥150 kg, pregnancy or breastfeeding, and severe β‑lactam allergy?

Ceftriaxone Dosing for STDs

For uncomplicated gonorrhea, use ceftriaxone 500 mg IM as a single dose plus azithromycin 1 g orally as a single dose, which provides dual coverage for both gonorrhea and presumptive chlamydial coinfection. 1, 2

Uncomplicated Gonorrhea (Urogenital, Anorectal, Pharyngeal)

Standard Dosing

• Ceftriaxone 500 mg IM single dose PLUS azithromycin 1 g orally single dose is the first-line regimen for all anatomic sites 1, 2
• This dual therapy addresses the 40-50% coinfection rate with chlamydia and helps delay emergence of cephalosporin resistance 1, 2
• The 500 mg dose is particularly critical for pharyngeal infections due to marked variability in cephalosporin clearance and protein binding in tonsillar tissue 1

Patients Weighing ≥150 kg

• Use the standard 500 mg dose—no dose adjustment is required based on weight alone 1
• Higher doses (up to 3 g per dose) have been used in China without treatment failures, and 2 g twice daily would achieve sufficient free plasma concentrations for high-level resistant strains 1

Pregnancy and Breastfeeding

• Use ceftriaxone 500 mg IM single dose PLUS azithromycin 1 g orally single dose—the same regimen as non-pregnant patients 1, 2
• Never use quinolones, tetracyclines, or doxycycline in pregnancy or lactation 3, 1

Severe β-Lactam Allergy

• Azithromycin 2 g orally as a single dose is the recommended alternative 2, 4
• This regimen has lower efficacy (only 93% cure rate) and causes significant gastrointestinal distress 1, 2
• Mandatory test-of-cure at 1 week is required with this regimen 2, 4
• Spectinomycin 2 g IM single dose is another option with 96.7% cure rate for urogenital infections, but has only 52% efficacy for pharyngeal infections and should never be used if pharyngeal exposure is suspected 1, 2, 4

Disseminated Gonococcal Infection (DGI)

While the provided evidence focuses primarily on uncomplicated gonorrhea, disseminated infection requires:

• Higher doses and prolonged therapy beyond single-dose regimens (specific DGI dosing not detailed in provided guidelines)
• Consultation with infectious disease specialists is recommended for treatment failures or complicated infections 2

Syphilis Treatment

The provided evidence does not contain specific ceftriaxone dosing recommendations for syphilis treatment. The guidelines focus exclusively on gonorrhea and chlamydia management. Syphilis screening should be performed at the time of gonorrhea diagnosis given overlapping risk factors 1, but treatment regimens are not addressed in these sources.

Critical Site-Specific Considerations

Pharyngeal Gonorrhea

• Pharyngeal infections are significantly more difficult to eradicate than urogenital or anorectal sites 1, 2
• Ceftriaxone 500 mg IM is the only reliably effective treatment for pharyngeal infections 1
• Spectinomycin achieves only 52% cure rate for pharyngeal gonorrhea 1, 2
• Gentamicin has only 20% cure rate for pharyngeal infections 1
• Oral cefixime 200 mg achieves only 78.9% cure rate for pharyngeal infections 1

Alternative Oral Regimen (When Ceftriaxone Unavailable)

• Cefixime 400 mg orally single dose PLUS azithromycin 1 g orally single dose 3, 2
• This regimen has inferior efficacy (97.4% vs 98.9% for ceftriaxone) 3
• Mandatory test-of-cure at 1 week is required with cefixime-based regimens 1, 2

Common Pitfalls to Avoid

Contraindicated Regimens

• Never use fluoroquinolones (ciprofloxacin, ofloxacin) due to widespread resistance, despite historical 99.8% cure rates 1, 2, 4
• Never use azithromycin 1 g alone for gonorrhea—it has only 93% efficacy and risks rapid resistance emergence 1, 2, 4
• Never use cefixime as monotherapy without azithromycin or doxycycline—this violates dual therapy recommendations 1

Follow-Up Requirements

• Patients treated with recommended ceftriaxone-based regimens do NOT need routine test-of-cure unless symptoms persist 1, 2, 4
• Mandatory test-of-cure at 1 week is required for patients receiving cefixime or azithromycin monotherapy 1, 2
• All patients should be retested at 3 months due to high reinfection risk 1, 2
• If symptoms persist, obtain culture with antimicrobial susceptibility testing and report to local health department within 24 hours 1, 2

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 1, 2, 4
• Patients and partners must abstain from sexual intercourse until therapy is completed and both are asymptomatic 1, 2, 4
• Expedited partner therapy with oral combination therapy (cefixime 400 mg plus azithromycin 1 g) may be considered when partners cannot be linked to timely evaluation, but this is not recommended for men who have sex with men (MSM) due to high risk of undiagnosed coexisting STDs or HIV 1, 2

Treatment Failure Management

• If treatment failure occurs, obtain specimens for culture and antimicrobial susceptibility testing immediately 1, 2
• Report the case to local public health officials within 24 hours 1
• Consult an infectious disease specialist 1, 2
• Recommended salvage regimens include gentamicin 240 mg IM PLUS azithromycin 2 g orally (single dose), spectinomycin 2 g IM PLUS azithromycin 2 g orally, or ertapenem 1 g IM for 3 days 1
• Most cases of ceftriaxone treatment failure involve the pharynx, not urogenital sites 1

Special Populations

Men Who Have Sex with Men (MSM)

• Use the same ceftriaxone 500 mg IM plus azithromycin 1 g orally regimen 1, 2
• Never use quinolones in MSM due to higher prevalence of resistant strains 1, 2
• Do not use patient-delivered partner therapy in MSM due to high risk of undiagnosed coexisting STDs or HIV 1

HIV-Infected Patients

• Use the same treatment regimen as HIV-negative patients 4
• Treatment is particularly vital to prevent increased HIV shedding and transmission risk 4
• Co-testing for HIV should be performed given facilitation of HIV transmission by gonorrhea 1