What is the recommended treatment for gonorrhea?

Treatment for Gonorrhea

Primary Recommendation

The recommended treatment for uncomplicated gonorrhea is ceftriaxone 500 mg intramuscularly in a single dose PLUS azithromycin 1 g orally in a single dose. 1, 2

This dual therapy regimen is the only recommended first-line treatment in the United States and should be administered together on the same day, preferably simultaneously and under direct observation. 1, 3

Rationale for Dual Therapy

The dual therapy approach addresses two critical clinical issues:

• Antimicrobial resistance: Combination therapy with two antimicrobials having different mechanisms of action improves treatment efficacy and potentially delays emergence and spread of cephalosporin resistance. 1, 2

• Chlamydia co-infection: Up to 40-50% of patients with gonorrhea are simultaneously infected with Chlamydia trachomatis, making presumptive treatment for both organisms essential. 1, 2

• Treatment efficacy: Ceftriaxone achieves a 99.1% cure rate for uncomplicated urogenital and anorectal gonorrhea, while azithromycin provides single-dose chlamydia coverage. 1

Alternative Regimens

When Ceftriaxone is Unavailable

Use cefixime 400 mg orally in a single dose PLUS azithromycin 1 g orally in a single dose. 1, 2

• Mandatory test-of-cure at 1 week is required with this regimen due to declining effectiveness of cefixime related to rising minimum inhibitory concentrations (MICs). 1, 2

For Severe Cephalosporin Allergy

Use azithromycin 2 g orally in a single dose. 1

• This regimen has lower efficacy (only 93%) and high gastrointestinal side effects. 1
• Mandatory test-of-cure at 1 week is required. 1

Alternative for Cephalosporin Allergy

Gentamicin 240 mg intramuscularly PLUS azithromycin 2 g orally (both single dose). 1

• This regimen achieved 100% cure rate in clinical trials. 1
• However, gentamicin has poor pharyngeal efficacy (only 20% cure rate). 1

Site-Specific Considerations

Pharyngeal Gonorrhea

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

• Ceftriaxone 500 mg intramuscularly is the only reliably effective treatment for pharyngeal infections and is strongly preferred over oral alternatives. 1
• Spectinomycin has only 52% efficacy for pharyngeal infections and should be avoided. 1
• Gentamicin also has poor pharyngeal efficacy. 1

Special Populations

Pregnant Women

Use ceftriaxone 500 mg intramuscularly PLUS azithromycin 1 g orally (both single dose). 1, 3

• Never use quinolones or tetracyclines in pregnancy. 1, 3
• Pregnant women with antenatal gonococcal infection should be retested in the third trimester unless recently treated. 3

Men Who Have Sex with Men (MSM)

Ceftriaxone is the only recommended treatment for MSM due to higher prevalence of resistant strains. 1, 2

• Never use quinolones for infections in MSM. 1
• Do not use patient-delivered partner therapy for MSM due to high risk of undiagnosed coexisting STDs or HIV. 1

Neonates

• Intravenous doses should be given over 60 minutes in neonates to reduce the risk of bilirubin encephalopathy. 4
• Ceftriaxone is contraindicated in premature neonates and in neonates (≤28 days) requiring calcium-containing IV solutions. 4

Critical Pitfalls to Avoid

Never Use These Regimens

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

• Never use azithromycin 1 g alone due to insufficient efficacy (only 93% cure rate). 1

• Never use spectinomycin for pharyngeal infections due to poor efficacy (only 52%). 1

Follow-Up Requirements

Test-of-Cure

Patients with uncomplicated gonorrhea treated with the recommended ceftriaxone plus azithromycin regimen do NOT need routine test-of-cure. 1, 2, 3

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

• Patients receiving cefixime plus azithromycin. 1
• Patients receiving azithromycin 2 g monotherapy. 1
• Patients with persistent symptoms after treatment. 1

Retesting for Reinfection

All patients should be retested 3 months after treatment due to high risk of reinfection. 1, 3

• Most repeat infections result from reinfection rather than treatment failure. 3

If Symptoms Persist

• Obtain culture with antimicrobial susceptibility testing immediately. 1, 2
• Report the case to local public health officials within 24 hours. 1
• Consult an infectious disease specialist. 1

Treatment Failure Management

If Treatment Failure Occurs

Recommended salvage regimens include: 1

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

Most cases of ceftriaxone treatment failure involve the pharynx, not urogenital sites. 1

Partner Management

All sexual partners from the preceding 60 days should be evaluated and treated. 1, 2

• Partners should receive the same dual therapy regimen for both gonorrhea and chlamydia. 1
• Patients should avoid sexual intercourse until therapy is completed and both they and their partners are asymptomatic. 1

Expedited Partner Therapy

Consider expedited partner therapy with oral combination therapy (cefixime 400 mg plus azithromycin 1 g) if partners cannot be linked to timely evaluation. 1

• This approach is NOT recommended for MSM due to high risk of undiagnosed coexisting STDs or HIV. 1

Additional Screening

Screen for syphilis with serology at the time of gonorrhea diagnosis. 1

Co-testing for HIV should also be performed given the facilitation of HIV transmission by gonorrhea. 1