What is the recommended treatment for gonorrhea?

Recommended Treatment for Gonorrhea

For uncomplicated gonorrhea at all anatomic sites (urogenital, anorectal, pharyngeal), administer ceftriaxone 500 mg intramuscularly as a single dose, plus doxycycline 100 mg orally twice daily for 7 days if chlamydial coinfection has not been excluded. 1, 2

Primary Treatment Regimen

The CDC updated its recommendations in 2020, increasing the ceftriaxone dose from 250 mg to 500 mg based on:

• Stable ceftriaxone MICs in U.S. surveillance data (< 0.1% with elevated MICs) 2
• Rapid rise in azithromycin resistance (nearly 5% of isolates with MIC ≥ 2.0 mcg/mL by 2018) 2
• New pharmacokinetic/pharmacodynamic data supporting higher dosing 2
• Antimicrobial stewardship concerns about routine dual therapy 1, 2

The shift from azithromycin to doxycycline as the companion drug reflects the rising azithromycin resistance and addresses the extremely common chlamydial coinfection (40-50% of gonorrhea cases). 3, 4

Critical Site-Specific Considerations

Pharyngeal gonorrhea is significantly more difficult to eradicate than urogenital or anorectal infections, making ceftriaxone the only reliably effective treatment for pharyngeal sites. 3, 4

• Spectinomycin has only 52% efficacy for pharyngeal infections 3
• Gentamicin shows only 20% cure rate for pharyngeal gonorrhea 3
• The 500 mg ceftriaxone dose provides superior pharyngeal coverage compared to lower doses 2

Alternative Regimens (When Ceftriaxone Unavailable)

If ceftriaxone is not available:

• Cefixime 400 mg orally single dose PLUS azithromycin 1 g orally single dose 3, 4
• Mandatory test-of-cure at 1 week is required due to declining cefixime effectiveness 3, 5

For severe cephalosporin allergy:

• Gentamicin 240 mg IM single dose PLUS azithromycin 2 g orally single dose (100% cure rate in clinical trials, but poor pharyngeal efficacy) 3
• Azithromycin 2 g orally alone is an option but has lower efficacy (93%) and high gastrointestinal side effects 3, 4

What NOT to Do: Critical Pitfalls

Never use fluoroquinolones (ciprofloxacin, ofloxacin) for gonorrhea treatment due to widespread resistance. 6, 3, 4

Never use azithromycin 1 g as monotherapy—it has insufficient efficacy (only 93% cure rate). 3

Never substitute oral cephalosporins for ceftriaxone in pharyngeal infections—they have markedly inferior efficacy. 3, 4

Special Populations

Pregnant Women

• Use ceftriaxone 500 mg IM PLUS azithromycin 1 g orally 3, 4
• Never use quinolones or tetracyclines in pregnancy 3, 4

Men Who Have Sex With Men (MSM)

• Only use ceftriaxone-based regimens due to higher prevalence of resistant strains 3
• Do not use patient-delivered partner therapy due to high risk of undiagnosed coexisting STDs or HIV 3

Patients With Recent Foreign Travel

• Use only ceftriaxone-based regimens due to international spread of resistant strains, particularly from Asia 7

Partner Management

All sexual partners from the preceding 60 days must be evaluated and treated with the same dual therapy regimen. 3, 4

• Partners should receive treatment for both gonorrhea and chlamydia regardless of testing results 3
• Patients must avoid sexual intercourse until therapy is completed and both partners are asymptomatic 3
• Expedited partner therapy may be considered if partners' treatment cannot be ensured 3

Follow-Up and Test-of-Cure

Patients treated with the recommended ceftriaxone 500 mg plus doxycycline regimen do NOT need routine test-of-cure unless symptoms persist. 3, 4, 1

However, all patients should be retested 3 months after treatment due to high reinfection rates. 3, 4

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

• Patients receiving cefixime-based regimens 3, 5
• Patients receiving azithromycin monotherapy 3
• Patients with persistent symptoms 3

Treatment Failure Management

If treatment failure is suspected:

1. Obtain specimens for culture and antimicrobial susceptibility testing immediately 3, 4
2. Report the case to local public health officials within 24 hours 3
3. Consult an infectious disease specialist 3, 4

Recommended salvage regimens:

• Gentamicin 240 mg IM PLUS azithromycin 2 g orally (single dose) 3
• Ertapenem 1 g IM for 3 days 3
• Spectinomycin 2 g IM PLUS azithromycin 2 g orally (if available) 3

Most ceftriaxone treatment failures involve pharyngeal sites, not urogenital sites. 3

Rationale for Current Approach

The evolution from dual therapy with azithromycin to conditional dual therapy with doxycycline reflects:

• Antimicrobial stewardship priorities to limit unnecessary azithromycin exposure 1, 2
• Rising azithromycin resistance (nearly 5% of U.S. isolates by 2018) 2
• Stable ceftriaxone susceptibility in U.S. surveillance (< 0.1% with elevated MICs) 2
• Need to address chlamydial coinfection (present in 40-50% of cases) 3, 4

The increased ceftriaxone dose to 500 mg provides a safety margin against emerging resistance while maintaining single-dose convenience. 1, 2