What is the recommended ceftriaxone (Ceftriaxone) dosage for treating gonorrhea?

Ceftriaxone Dosage for Gonorrhea

The recommended ceftriaxone dose for uncomplicated gonorrhea is 500 mg intramuscularly as a single dose, combined with azithromycin 1 g orally as a single dose. 1, 2, 3

Standard Treatment Regimen

• Ceftriaxone 500 mg IM single dose PLUS azithromycin 1 g orally single dose is the first-line treatment for uncomplicated gonococcal infections of the cervix, urethra, rectum, and pharynx. 1, 2, 3

• The FDA label indicates 250 mg IM as the approved dose for uncomplicated gonococcal infections, but current CDC guidelines have increased this to 500 mg due to antimicrobial stewardship concerns and evolving resistance patterns. 4, 3

• The 500 mg dose represents an evidence-based increase from the older 250 mg recommendation to ensure adequate treatment efficacy, particularly for pharyngeal infections which are significantly more difficult to eradicate. 1, 2, 3

Critical Rationale for Dual Therapy

• Azithromycin 1 g must be added to address potential chlamydial coinfection (present in 40-50% of gonorrhea cases) and to potentially delay emergence of cephalosporin resistance. 1, 2

• Never use azithromycin 1 g alone for gonorrhea treatment, as it has only 93% efficacy, which is inadequate. 1, 5

• If chlamydial infection has been definitively excluded through testing, doxycycline 100 mg orally twice daily for 7 days may be substituted for azithromycin. 3

Site-Specific Considerations

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

• Ceftriaxone 500 mg IM has superior efficacy for pharyngeal infections compared to all oral alternatives, with a 99.1% cure rate. 1, 2

• The 500 mg dose is particularly important for pharyngeal infections because extended-spectrum cephalosporins have marked variability in clearance and half-life within pharyngeal tissues, with nearly 90% being protein-bound in tonsillar tissue. 6

Alternative Regimens When Ceftriaxone Unavailable

• If ceftriaxone is not available, use cefixime 400 mg orally single dose PLUS azithromycin 1 g orally single dose, with mandatory test-of-cure at 1 week. 1

• Cefixime is less effective than ceftriaxone, particularly for pharyngeal infections, and rising cefixime MICs have resulted in declining effectiveness. 1

Severe Cephalosporin Allergy

• For patients with severe cephalosporin allergy, use azithromycin 2 g orally as a single dose (not split), with mandatory test-of-cure at 1 week. 1, 2, 5

• The 2 g azithromycin dose should not be split, as this would reduce peak serum concentrations and tissue penetration, potentially compromising efficacy. 5

• This regimen has lower efficacy (93%) and high gastrointestinal side effects (35.3% of patients experience GI symptoms). 5, 7

Higher Doses for Treatment Failure or Resistant Strains

• For suspected ceftriaxone treatment failure, recommended salvage regimens include gentamicin 240 mg IM PLUS azithromycin 2 g orally (single dose), or ertapenem 1 g IM for 3 days. 6, 1

• Pharmacodynamic studies suggest that ceftriaxone 1 g single dose may be necessary to eradicate low-level ceftriaxone-resistant strains (MIC 0.5 mg/L), particularly for pharyngeal infections. 8

• Higher doses of ceftriaxone (up to 3 g per dose with repeat dosing) are used in China without reported treatment failures, and a twice-daily dose of 2 g ceftriaxone would achieve sufficient free plasma concentrations for high-level resistant strains. 6

Critical Pitfalls to Avoid

• Never use fluoroquinolones (ciprofloxacin, ofloxacin) for gonorrhea treatment due to widespread resistance. 1, 2

• Never use spectinomycin for pharyngeal infections, as it has only 52% efficacy at this site. 1, 2

• Never use gentamicin alone for pharyngeal infections, as it has only 20% cure rate at this site. 1, 2

• Do not use diluents containing calcium (Ringer's solution, Hartmann's solution) to reconstitute ceftriaxone, as particulate formation can result. 4

Special Populations

• Pregnant women: Use the standard regimen of ceftriaxone 500 mg IM PLUS azithromycin 1 g orally; never use quinolones or tetracyclines in pregnancy. 1, 2

• Men who have sex with men (MSM): Only use ceftriaxone (never quinolones) due to higher prevalence of resistant strains. 1, 2

• Neonates: Ceftriaxone is contraindicated in premature neonates and in neonates ≤28 days requiring calcium-containing IV solutions due to risk of ceftriaxone-calcium precipitation. 4

Follow-Up Requirements

• Patients treated with the recommended ceftriaxone 500 mg IM + azithromycin 1 g regimen do not need routine test-of-cure unless symptoms persist. 1, 2

• Consider retesting at 3 months due to high reinfection risk (not to assess treatment efficacy). 1, 2

• If symptoms persist after treatment, obtain culture with antimicrobial susceptibility testing and report to public health within 24 hours. 1, 2

Partner Management

• All sexual partners from the preceding 60 days should be evaluated and treated with the same dual therapy regimen. 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 this is not recommended for MSM due to high risk of undiagnosed coexisting STDs or HIV. 1