Gonorrhea Treatment Recommendations

First-Line Treatment for Uncomplicated Gonorrhea

The recommended treatment is 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 single-dose therapy is preferred for compliance). 1, 2, 3, 4

Rationale for This Regimen

Ceftriaxone achieves a 99.1% cure rate for uncomplicated urogenital, anorectal, and pharyngeal gonorrhea 2
The dual therapy addresses the 40-50% co-infection rate with Chlamydia trachomatis that occurs in gonorrhea patients 1, 2, 3
Combination therapy with different mechanisms of action helps prevent antimicrobial resistance development 1, 2
The 500 mg dose (increased from the previous 250 mg recommendation) provides superior efficacy, particularly for pharyngeal infections where cephalosporins have marked variability in tissue penetration 2, 4

Choice Between Doxycycline and Azithromycin for Chlamydia Coverage

Doxycycline 100 mg orally twice daily for 7 days is now preferred over azithromycin due to increasing azithromycin resistance and antimicrobial stewardship concerns 3, 4
Azithromycin 1 g orally as a single dose remains acceptable when single-dose therapy is essential for compliance 1, 2, 3
Azithromycin 1 g alone has only 93% efficacy for gonorrhea and should never be used as monotherapy 2, 3

Treatment in Pregnancy

Pregnant women must receive ceftriaxone 500 mg intramuscularly PLUS azithromycin 1 g orally as a single dose. 1, 2, 3, 5, 6

Critical Contraindications in Pregnancy

Never use quinolones (ciprofloxacin, ofloxacin) in pregnancy due to potential fetal harm 1, 2
Never use tetracyclines (doxycycline) in pregnancy due to fetal toxicity 7, 1, 2, 3
Never use erythromycin estolate in pregnancy due to drug-related hepatotoxicity 1

Alternative Chlamydia Treatment in Pregnancy

If azithromycin cannot be used, alternatives include amoxicillin 500 mg orally three times daily for 7 days or erythromycin base 500 mg orally four times daily for 7 days 1

Follow-Up in Pregnancy

Pregnant women with antenatal gonococcal infection should be retested in the third trimester unless recently treated 5, 6

Treatment for Patients with Cephalosporin Allergy

For patients with severe cephalosporin allergy, use azithromycin 2 g orally as a single dose with mandatory test-of-cure at 1 week. 7, 2

Important Limitations of This Alternative

This regimen has lower efficacy (only 93%) compared to ceftriaxone-based therapy 2
High gastrointestinal side effects are common with the 2 g azithromycin dose 2
Test-of-cure is mandatory at 1 week post-treatment using culture (preferred) or nucleic acid amplification testing 2

Other Alternative for Cephalosporin Allergy

Gentamicin 240 mg intramuscularly PLUS azithromycin 2 g orally as a single dose achieved 100% cure rates in clinical trials 2, 8
However, gentamicin has poor efficacy for pharyngeal infections (only 20% cure rate), so avoid if pharyngeal infection is present 2
Spectinomycin 2 g intramuscularly is another alternative but is no longer widely available in the United States and has only 52% efficacy for pharyngeal gonorrhea 7, 1, 2

Alternative Regimen When Ceftriaxone is Unavailable

If ceftriaxone is unavailable, use cefixime 400 mg orally as a single dose PLUS azithromycin 1 g orally (or doxycycline 100 mg twice daily for 7 days). 7, 2, 9

Critical Requirements for Cefixime-Based Regimens

Mandatory test-of-cure at 1 week is required due to rising cefixime minimum inhibitory concentrations and declining effectiveness 2
Cefixime has lower efficacy (97.4% cure rate) compared to ceftriaxone (98.9% cure rate) 2
Oral cephalosporins were removed from first-line recommendations in 2012 due to documented treatment failures in Europe 2

Site-Specific Considerations

Pharyngeal Gonorrhea

Pharyngeal infections are significantly more difficult to eradicate than urogenital or anorectal infections 2, 3
Ceftriaxone 500 mg intramuscularly is the only reliably effective treatment for pharyngeal gonorrhea 2, 3
Spectinomycin has only 52% efficacy for pharyngeal infections 7, 2
Gentamicin has only 20% efficacy for pharyngeal infections 2
Most ceftriaxone treatment failures involve the pharynx, not urogenital sites 2

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 for MSM due to widespread resistance in this population 2
Do not use patient-delivered partner therapy for MSM due to high risk of undiagnosed coexisting sexually transmitted diseases or HIV 2

Patients with Recent Foreign Travel

Ceftriaxone 500 mg intramuscularly is the superior choice due to increased risk of resistant strains acquired internationally 2

Partner Management

All sexual partners from the preceding 60 days must be evaluated and treated with the same dual therapy regimen, regardless of symptoms or test results. 1, 2, 3

Key Partner Management Principles

Partners should receive treatment even if asymptomatic, as untreated partners lead to reinfection in up to 20% of cases 1
Patients must abstain from sexual intercourse until therapy is completed and both partners are treated 1, 2
Never assume partners were treated—directly verify or use expedited partner therapy strategies 1
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 2
Expedited partner therapy is not recommended for MSM due to high risk of undiagnosed coexisting sexually transmitted diseases or HIV 2

Follow-Up Requirements

Routine Follow-Up

Patients treated with the recommended ceftriaxone 500 mg regimen do not need routine test-of-cure unless symptoms persist 2, 3, 5, 6
All patients should be retested at 3 months after treatment due to high reinfection risk (most post-treatment infections result from reinfection rather than treatment failure) 2, 3, 5, 6

Mandatory Test-of-Cure Situations

Mandatory test-of-cure at 1 week is required for:
- Patients treated with cefixime-based regimens 2
- Patients treated with azithromycin 2 g monotherapy (cephalosporin allergy) 2
- Patients with persistent symptoms after treatment 2, 3

Test-of-Cure Methodology

Culture is preferred for test-of-cure as it allows antimicrobial susceptibility testing 2
If nucleic acid amplification testing is used and positive, confirm with culture and perform phenotypic antimicrobial susceptibility testing 2

Treatment Failure Management

If treatment failure is suspected (persistent symptoms after recommended therapy), immediately obtain specimens for culture with antimicrobial susceptibility testing, report to local public health officials within 24 hours, and consult an infectious disease specialist. 2

Salvage Regimens for Treatment Failure

Gentamicin 240 mg intramuscularly PLUS azithromycin 2 g orally as a single dose 2, 3
Ertapenem 1 g intramuscularly for 3 days 2, 3
Higher doses of ceftriaxone (up to 2-3 g per dose with repeat dosing) have been used successfully in other countries 2

Additional Screening Recommendations

Screen for syphilis with serology at the time of gonorrhea diagnosis 2
Co-test for HIV given that gonorrhea facilitates HIV transmission 2, 4

Critical Pitfalls to Avoid

Never use fluoroquinolones (ciprofloxacin, ofloxacin) for gonorrhea treatment due to widespread resistance, despite their historical 99.8% cure rates 2, 3, 4
Never use azithromycin 1 g alone for gonorrhea as it has only 93% efficacy and risks rapid resistance emergence 2, 3
Never delay treatment waiting for culture results if compliance with follow-up is uncertain—treat presumptively based on clinical diagnosis 1
Never use doxycycline, quinolones, or tetracyclines in pregnancy 7, 1, 2, 3
Never use cefixime as monotherapy without azithromycin or doxycycline as this violates dual therapy recommendations 2

What are the recommended medications for treating gonorrhea, considering various patient factors such as pregnancy and allergy history?

Help us tailor your experience