What is the recommended management of uncomplicated gonorrhea, including ceftriaxone dosing (500 mg intramuscular, 1 g intramuscular if weight ≥150 kg), chlamydia co‑treatment, alternative regimens for ceftriaxone allergy, and considerations in pregnancy or lactation?

Treatment for Gonorrhea

Primary Recommendation

For uncomplicated gonorrhea, administer ceftriaxone 500 mg intramuscularly as a single dose PLUS azithromycin 1 g orally as a single dose. This dual therapy regimen is the current CDC-recommended first-line treatment for all anatomic sites including cervical, urethral, rectal, and pharyngeal infections. 1, 2, 3

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Rationale for Current Regimen

• Ceftriaxone 500 mg IM achieves a 99.1% cure rate for uncomplicated urogenital and anorectal gonorrhea, making it the most effective single agent available. 1, 2

• The 500 mg dose (rather than the historical 125-250 mg) is now standard to maintain a therapeutic reserve against emerging resistance patterns and ensure adequate bactericidal levels, particularly for pharyngeal infections. 1, 3

• Dual therapy with azithromycin addresses two critical issues: (1) co-infection with Chlamydia trachomatis occurs in 40-50% of gonorrhea cases, and (2) combination therapy may delay emergence of cephalosporin resistance. 1, 2

• Azithromycin 1 g as a single dose is the only true single-dose option for chlamydia coverage; if azithromycin cannot be used, doxycycline 100 mg orally twice daily for 7 days is required. 1

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Dosing Adjustment for Higher Body Weight

• For patients weighing ≥150 kg (330 lbs), increase ceftriaxone to 1 g intramuscularly to ensure adequate tissue penetration and bactericidal activity. 1

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Alternative Regimens When Ceftriaxone Is Unavailable

• Cefixime 400 mg orally single dose PLUS azithromycin 1 g orally single dose is acceptable when injectable ceftriaxone cannot be administered. 1, 2, 4

• Critical limitation: Cefixime achieves only a 97.4% overall cure rate and just 78.9% for pharyngeal infections, compared to ceftriaxone's 99.1%. 1, 4

• Mandatory test-of-cure at 1 week is required for all patients treated with cefixime-based regimens due to inferior efficacy. 1, 2

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Severe Cephalosporin Allergy

• For patients with documented severe cephalosporin allergy, use gentamicin 240 mg intramuscularly PLUS azithromycin 2 g orally (single dose). This regimen achieved 100% cure rates in clinical trials. 2

• Alternative option: Azithromycin 2 g orally as monotherapy, but this has only 93% efficacy and causes significant gastrointestinal distress. 1, 2

• Spectinomycin 2 g intramuscularly may be used for urogenital infections but has only 52% efficacy for pharyngeal gonorrhea and should never be used if pharyngeal exposure is suspected. 1, 2

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Site-Specific Considerations

Pharyngeal Gonorrhea

• Pharyngeal infections are significantly more difficult to eradicate than urogenital or anorectal infections. 1, 2

• Ceftriaxone 500 mg IM is the only reliably effective treatment for pharyngeal gonorrhea; oral cephalosporins like cefixime cure only 78.9% of pharyngeal infections. 1, 2

• Never use spectinomycin for pharyngeal infections due to its 52% cure rate at this site. 1, 2

Gonococcal Conjunctivitis

• Treat with ceftriaxone 1 g intramuscularly as a single dose and perform a single saline lavage of the affected eye. 5, 2

Disseminated Gonococcal Infection (DGI)

• Hospitalization is recommended for initial therapy, especially for patients with purulent synovial effusions, uncertain diagnosis, or poor compliance. 5

• Initial regimen: 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. 5, 2

• Assess for endocarditis and meningitis as part of the evaluation. 5, 2

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Pregnancy and Lactation

• Pregnant and lactating patients should receive ceftriaxone 500 mg IM PLUS azithromycin 1 g orally as the preferred regimen. 1, 2, 6

• Absolutely contraindicated in pregnancy: Quinolones (ciprofloxacin, ofloxacin, levofloxacin), tetracyclines, and doxycycline due to fetal safety concerns. 1, 2, 4, 6

• If severe cephalosporin allergy exists in pregnancy, use spectinomycin 2 g IM PLUS azithromycin 1 g orally, though pharyngeal efficacy remains poor. 2

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Absolutely Contraindicated Medications

• Fluoroquinolones (ciprofloxacin, ofloxacin, levofloxacin) are absolutely contraindicated for gonorrhea treatment due to widespread resistance, despite historical cure rates of 99.8%. 1, 2, 4

• Azithromycin 1 g alone should never be used for gonorrhea due to insufficient efficacy (only 93% cure rate) and risk of rapid resistance emergence. 1, 2

• Quinolones are also contraindicated in persons ≤17 years of age based on animal study data. 5, 4

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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 + azithromycin 1 g orally), regardless of symptoms or test results. 1, 2

• If the most recent sexual contact occurred >60 days before symptom onset, treat the most recent partner. 2

• Expedited partner therapy (EPT) with oral cefixime 400 mg + azithromycin 1 g may be considered when partners cannot be linked to timely evaluation. 2

• EPT should NOT be used for men who have sex with men (MSM) due to high risk of undiagnosed coexisting STDs or HIV. 2

• Patients must abstain from sexual intercourse until therapy is completed and both patient and all partners are asymptomatic. 1, 2

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Follow-Up and Test-of-Cure

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

• Mandatory test-of-cure at 1 week is required for:

  • Patients treated with cefixime-based regimens 1, 2
  • Patients treated with azithromycin monotherapy 1, 2
  • Patients with suspected pharyngeal infection treated with spectinomycin 2

• Retest all patients at 3 months due to high reinfection risk (most post-treatment positive tests represent reinfection, not treatment failure). 2, 3

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

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Special Populations

Men Who Have Sex with Men (MSM)

• Ceftriaxone is the only recommended treatment for MSM due to higher prevalence of resistant strains. 2

• Never use quinolones in MSM due to resistance patterns. 2

Patients with Recent Foreign Travel

• Ceftriaxone 500 mg IM is the only recommended treatment for patients with history of recent foreign travel due to increased risk of resistant strains. 2

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Ancillary Screening

• Screen for syphilis by serology at the time of gonorrhea diagnosis given high rates of co-infection and overlapping risk factors. 1, 2

• Co-test for HIV as gonorrhea facilitates HIV transmission. 2, 3

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Common Pitfalls to Avoid

• Never use oral cephalosporins other than cefixime (such as cefuroxime or cefpodoxime) as they are ineffective for pharyngeal infections. 1

• Never assume symptom resolution equals cure when suboptimal regimens were used—test-of-cure is mandatory for cefixime or azithromycin monotherapy. 2

• Do not omit chlamydia treatment even when chlamydia testing is negative in a patient with gonorrhea, due to the 40-50% co-infection rate. 1, 2

• Most post-treatment gonorrhea detections represent reinfection rather than treatment failure, emphasizing the importance of partner treatment. 2