What is the recommended treatment for gonorrhea (gonococcal infection)?

Recommended Treatment for Gonorrhea

Treat all patients with uncomplicated gonorrhea using ceftriaxone 250 mg intramuscularly PLUS azithromycin 1 g orally as a single dose, administered together on the same day, preferably simultaneously and under direct observation. 1, 2, 3

Primary Treatment Regimen

• Ceftriaxone 250 mg IM (single dose) + Azithromycin 1 g orally (single dose) is the only CDC-recommended first-line regimen for uncomplicated gonococcal infections of the cervix, urethra, rectum, and pharynx 1, 2
• This dual therapy achieves a 99.1% cure rate for urogenital and anorectal gonorrhea 1
• Azithromycin is preferred over doxycycline due to single-dose convenience, better compliance, and substantially lower gonococcal resistance to azithromycin compared to tetracyclines 1

Rationale for Dual Therapy

The combination approach serves two critical purposes:

• Addresses antimicrobial resistance: Dual therapy with different mechanisms of action improves treatment efficacy and potentially delays emergence and spread of cephalosporin resistance 1
• Treats chlamydial co-infection: Up to 40-50% of gonorrhea patients have concurrent chlamydia, making presumptive treatment essential 1

Alternative Regimens (When Ceftriaxone Unavailable)

If ceftriaxone cannot be administered:

• Cefixime 400 mg orally (single dose) + Azithromycin 1 g orally (single dose) 1, 4
  • Mandatory test-of-cure at 1 week is required due to declining cefixime susceptibility and documented treatment failures in Europe 1, 4
  • This oral alternative is less effective than ceftriaxone due to rising minimum inhibitory concentrations 4

Severe Cephalosporin Allergy

For patients with documented severe cephalosporin allergy:

• Azithromycin 2 g orally (single dose) 1, 5

  • Achieves 96-99% cure rates but has lower efficacy than ceftriaxone-based regimens 4
  • Do NOT split the 2 g dose—splitting reduces peak serum concentrations and tissue penetration, compromising efficacy 5
  • High gastrointestinal side effects are common 1
  • Mandatory test-of-cure at 1 week with culture preferred to allow antimicrobial susceptibility testing 5

• Alternative: Gentamicin 240 mg IM (single dose) + Azithromycin 2 g orally (single dose) 1, 6

  • Achieved 100% cure rate in clinical trials for urogenital infections 6
  • Caution: Poor pharyngeal efficacy (only 20% cure rate in one study) 1

Site-Specific Considerations

Pharyngeal gonorrhea requires special attention:

• Pharyngeal infections are significantly more difficult to eradicate than urogenital or anorectal infections 1
• Ceftriaxone is the only reliably effective treatment for pharyngeal gonorrhea 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 the same ceftriaxone 250 mg IM + azithromycin 1 g orally regimen as non-pregnant patients 1, 2
• Never use quinolones or tetracyclines during pregnancy 1
• Retest in the third trimester unless recently treated 2, 3

Men Who Have Sex with Men (MSM)

• Ceftriaxone is the only recommended treatment due to higher prevalence of resistant strains 1
• Do not use quinolones in this population 1
• Do not use patient-delivered partner therapy due to high risk of undiagnosed coexisting STDs or HIV 1

HIV-Infected Patients

• Use identical treatment regimens as HIV-negative patients 4
• Treatment is particularly vital because gonococcal infection increases HIV shedding and transmission risk 4

Critical Pitfalls to Avoid

Never Use These Regimens:

• Fluoroquinolones (ciprofloxacin, ofloxacin): Widespread resistance has rendered them unreliable despite historical 99.8% cure rates 1, 7
• Azithromycin 1 g monotherapy: Only 93% efficacy—inadequate as standalone treatment 1, 5
• Cefixime as first-line therapy: No longer recommended due to declining susceptibility and documented treatment failures 7, 1

Dosing Errors:

• Do not use ceftriaxone doses lower than 250 mg 1
• If using azithromycin monotherapy (severe allergy only), the dose must be 2 g, not 1 g 5

Partner Management

All sexual partners from the preceding 60 days must be evaluated and treated:

• Partners should receive the same dual therapy regimen for both gonorrhea and chlamydia, regardless of symptoms 1, 4
• Patients and all partners must abstain from sexual intercourse until therapy is completed and both parties are asymptomatic 1, 4
• Consider expedited partner therapy with oral combination therapy (cefixime 400 mg + azithromycin 1 g) if partners cannot be linked to timely evaluation 1

Test-of-Cure Requirements

Routine test-of-cure is NOT necessary for:

• Patients treated with recommended ceftriaxone-based regimens who become asymptomatic 1, 2

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

• Patients receiving cefixime-based regimens 1, 4
• Patients receiving azithromycin 2 g monotherapy 5
• Any patient with persistent symptoms after treatment 1, 4

For persistent symptoms:

• Obtain culture from the site of infection and perform antimicrobial susceptibility testing 1, 4
• Report treatment failures to public health authorities within 24 hours 1
• Consult an infectious disease specialist 1

Retesting Recommendations

• Retest all patients 3 months after treatment due to high risk of reinfection (most infections after treatment are reinfections, not treatment failures) 2, 3
• If nucleic acid amplification testing is positive at follow-up, confirm with culture and perform phenotypic antimicrobial susceptibility testing 1

Additional Screening

• Screen for syphilis with serology at the time of gonorrhea diagnosis 1
• Co-test for HIV given that gonorrhea facilitates HIV transmission 1