What is the recommended first‑line regimen and dosing for uncomplicated gonorrhea in an adult without a cephalosporin allergy, including weight‑based ceftriaxone dose and coverage for possible Chlamydia trachomatis co‑infection?

Recommended First-Line Treatment for Uncomplicated Gonorrhea

For uncomplicated gonorrhea in adults without cephalosporin allergy, administer ceftriaxone 500 mg intramuscularly as a single dose PLUS doxycycline 100 mg orally twice daily for 7 days (or azithromycin 1 g orally as a single dose if chlamydial infection has not been excluded). 1

Core Treatment Regimen

• Ceftriaxone 500 mg IM single dose is the only recommended first-line agent, achieving a 99.1% cure rate for uncomplicated urogenital, anorectal, and pharyngeal gonorrhea. 2, 3
• The dose was increased from 250 mg to 500 mg in 2020 to maintain a therapeutic reserve against emerging resistance patterns. 1, 3
• Ceftriaxone is the only reliably effective treatment for pharyngeal gonorrhea, where oral alternatives cure only 78.9% of infections compared to ceftriaxone's superior efficacy. 2, 4

Mandatory Concurrent Chlamydia Coverage

• Add doxycycline 100 mg orally twice daily for 7 days if chlamydial infection has not been excluded by testing. 1, 2
• Alternatively, azithromycin 1 g orally as a single dose may be used for chlamydia coverage, offering better compliance but with antimicrobial stewardship concerns. 3, 2
• Co-infection with Chlamydia trachomatis occurs in 20–50% of gonorrhea cases, making presumptive dual therapy essential. 3
• Never use azithromycin 1 g alone for gonorrhea—it achieves only 93% efficacy and risks rapid resistance emergence. 2, 3

Weight-Based Dosing Considerations

• No weight-based adjustment is required for adults; the standard 500 mg IM dose is used regardless of body weight. 5, 1
• In pediatric patients, the dose is 50 mg/kg (not to exceed 1 gram) for uncomplicated infections. 5

Critical Administration Details

• Inject ceftriaxone deeply into a large muscle mass (e.g., gluteus maximus or lateral thigh); aspiration before injection helps avoid inadvertent intravascular administration. 5
• Do not use diluents containing calcium (e.g., Ringer's solution) for reconstitution, as precipitation can occur. 5
• Reconstitute the 500 mg vial with 1.8 mL of diluent to achieve a concentration of 250 mg/mL. 5

Absolutely Contraindicated Alternatives

• Fluoroquinolones (ciprofloxacin, ofloxacin, levofloxacin) are completely contraindicated due to widespread resistance, despite historical cure rates exceeding 99%. 6, 2, 3
• Spectinomycin achieves only 52% cure for pharyngeal infections and should never be used when pharyngeal exposure is possible. 3, 4
• Gentamicin has only 20% efficacy for pharyngeal gonorrhea and is unreliable for this site. 2

Alternative Regimens (When Ceftriaxone Unavailable)

• Cefixime 400 mg orally single dose PLUS azithromycin 1 g orally single dose is acceptable only when ceftriaxone cannot be obtained. 6, 3
• Mandatory test-of-cure at 1 week is required for all patients receiving cefixime due to rising minimum inhibitory concentrations and declining effectiveness (97.4% overall cure rate, only 78.9% for pharyngeal infections). 2, 3, 7
• Cefixime provides lower and less sustained bactericidal levels than ceftriaxone, contributing to reduced efficacy. 3

Severe Cephalosporin Allergy

• For documented severe cephalosporin allergy, use azithromycin 2 g orally as a single dose with mandatory test-of-cure at 1 week. 2, 3
• This regimen has lower efficacy (93%) and high gastrointestinal side effects (35.3% of patients, with 2.9% experiencing severe symptoms). 2, 8
• Gentamicin 240 mg IM PLUS azithromycin 2 g orally achieved 100% cure in clinical trials but should be reserved for true allergy cases. 3

Partner Management Requirements

• Evaluate and treat all sexual partners from the preceding 60 days with the same dual therapy regimen (ceftriaxone 500 mg IM + doxycycline or azithromycin), regardless of symptoms or test results. 2, 3, 4
• If the last sexual contact occurred more than 60 days before diagnosis, treat the most recent partner. 3
• Patients must abstain from sexual intercourse until therapy is completed and both patient and all partners are asymptomatic. 2, 3
• Expedited partner therapy with oral cefixime 400 mg plus azithromycin 1 g may be considered when partners cannot access timely evaluation, but never for men who have sex with men (MSM) due to high risk of undiagnosed HIV or other STDs. 3

Special Population Considerations

Pregnancy

• Use the standard regimen: ceftriaxone 500 mg IM PLUS azithromycin 1 g orally as a single dose. 3, 4
• Absolutely avoid quinolones, tetracyclines, and doxycycline in pregnancy due to fetal safety concerns. 2, 3
• If severe cephalosporin allergy is documented, use spectinomycin 2 g IM plus azithromycin 1 g orally, though pharyngeal efficacy remains poor. 3

Men Who Have Sex with Men (MSM)

• Only ceftriaxone is recommended for MSM; never use quinolones due to higher prevalence of resistant strains in this population. 3, 4
• Do not offer expedited partner therapy to MSM due to high risk of undiagnosed coexisting STDs or HIV. 3

HIV-Infected Patients

• Use identical treatment regimens as HIV-negative patients; no dose adjustment is required. 2, 3

Follow-Up and Test-of-Cure

• Patients treated with the recommended ceftriaxone 500 mg IM regimen do not require routine test-of-cure unless symptoms persist. 2, 3, 4
• Consider retesting all patients at 3 months due to high reinfection risk (most post-treatment positive tests represent reinfection rather than treatment failure). 3
• If symptoms persist after treatment, obtain culture specimens immediately from all infected anatomic sites with antimicrobial susceptibility testing. 2, 3

Additional Mandatory Screening

• Screen for syphilis with serology at the time of gonorrhea diagnosis. 3, 4
• Perform HIV testing given that gonorrhea facilitates HIV transmission. 3, 4
• Test for other sexually transmitted infections as clinically indicated. 2

Treatment Failure Management

• If treatment failure is suspected, obtain culture with antimicrobial susceptibility testing immediately and report the case to local public health officials within 24 hours. 2, 3
• Consult an infectious disease specialist for guidance on salvage therapy. 2, 3
• Recommended salvage regimens include gentamicin 240 mg IM plus azithromycin 2 g orally or ertapenem 1 g IM for 3 days. 2, 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 for this site. 2, 3, 4
• For gonococcal conjunctivitis, use ceftriaxone 1 g IM single dose plus a single saline eye lavage. 6, 3
• Disseminated gonococcal infection requires hospitalization with ceftriaxone 1 g IM or IV every 24 hours for 24–48 hours until clinical improvement, then switch to oral therapy to complete 1 week total. 6, 3