What is the recommended treatment for gonorrhea?

Gonorrhea: Investigations and Treatment

Recommended First-Line Treatment

Treat all patients with uncomplicated gonorrhea with ceftriaxone 250 mg intramuscularly PLUS azithromycin 1 g orally, both given as single doses on the same day, preferably simultaneously and under direct observation. 1

This dual therapy approach is the only CDC-recommended first-line regimen and addresses both gonorrhea and likely chlamydial co-infection, which occurs in 40-50% of cases 1. Azithromycin is strongly preferred over doxycycline due to single-dose convenience, better compliance, and substantially lower gonococcal resistance to azithromycin compared to tetracyclines 1.

Diagnostic Testing Approach

Initial Testing

• Use nucleic acid amplification testing (NAAT) for diagnosis, as it offers sensitivity and specificity comparable to culture for urogenital specimens 2
• Urine NAAT is acceptable and performs as well as urethral or cervical swabs 2
• Obtain culture specimens when possible to maintain antimicrobial resistance surveillance capacity, as NAAT-only testing has led to declining culture capability nationwide 3

Concurrent Testing Requirements

• Screen for syphilis with serology at the time of gonorrhea diagnosis 4
• Test for HIV and other sexually transmitted infections, given high co-infection rates 2
• Presume chlamydial co-infection and treat empirically even if NAAT is negative at time of treatment 3, 1

Alternative Regimens (When Ceftriaxone Unavailable)

If Ceftriaxone Not Readily Available

Use cefixime 400 mg orally PLUS azithromycin 1 g orally as single doses 3, 1

Critical caveat: Cefixime is less effective than ceftriaxone, particularly for pharyngeal infections (only 91% cure rate for pharyngeal gonorrhea) 4, 5. Mandatory test-of-cure at 1 week is required for all patients receiving this regimen 3, 1.

For Severe Cephalosporin Allergy

Administer azithromycin 2 g orally as a single dose 3, 6

This regimen has important limitations:

• Lower efficacy (only 93% cure rate) compared to ceftriaxone-based therapy 1, 7
• High gastrointestinal side effects (35% of patients experience GI symptoms, with 10% moderate and 3% severe) 7
• Mandatory test-of-cure at 1 week 6
• Consult infectious disease specialist due to limited data on this alternative 6

Emerging Alternative for Cephalosporin Allergy

Gentamicin 240 mg intramuscularly PLUS azithromycin 2 g orally achieved 100% cure rate in clinical trials, including 10 of 10 pharyngeal infections 8. However, gastrointestinal adverse events were common and may limit routine use 8.

Site-Specific Considerations

Pharyngeal Gonorrhea

• 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
• Cefixime has only 91% efficacy for pharyngeal sites 5
• Spectinomycin and gentamicin have poor pharyngeal efficacy (only 2 of 10 cured with gentamicin monotherapy) 1

Rectal Gonorrhea

Ceftriaxone-based dual therapy remains first-line 1. Alternative regimens (gentamicin/azithromycin, gemifloxacin/azithromycin) showed 100% cure rates for rectal infections in limited studies 8.

Special Populations

Men Who Have Sex with Men (MSM)

Use only ceftriaxone-based therapy due to higher prevalence of resistant strains in this population 4, 1. Never use quinolones for MSM 1.

Pregnant Women

Ceftriaxone is the preferred and only recommended treatment 4, 1. Contraindications in pregnancy:

• Quinolones (absolutely contraindicated) 1
• Tetracyclines including doxycycline (contraindicated) 1, 6
• Use erythromycin or amoxicillin for chlamydial co-infection instead of azithromycin if needed 6

Patients with Recent Foreign Travel

Use only ceftriaxone-based therapy due to higher likelihood of resistant strains 1.

Test-of-Cure Requirements

When Test-of-Cure is NOT Needed

Patients with uncomplicated urogenital or rectal gonorrhea treated with recommended ceftriaxone-based dual therapy do not require routine test-of-cure 1, 9.

When Test-of-Cure is MANDATORY (at 1 week)

• All patients receiving cefixime-based regimens 3, 1
• All patients receiving azithromycin 2 g monotherapy 6
• All patients with pharyngeal gonorrhea treated with alternative regimens 1
• Patients with persistent symptoms after any treatment 3, 1

Test-of-Cure Methodology

• Culture is preferred as it allows antimicrobial susceptibility testing 6
• NAAT acceptable if culture unavailable, but positive NAAT requires confirmatory culture 3

Treatment Failure Management

If Treatment Failure Occurs

1. Obtain culture specimens immediately with antimicrobial susceptibility testing 3, 1, 6
2. Report case to local/state health department within 24 hours 3, 6
3. Consult infectious disease specialist immediately 3, 6
4. Re-treat with ceftriaxone 250 mg IM PLUS azithromycin 2 g orally 3

Alternative Regimens for Suspected Ceftriaxone Failure

• Gentamicin 240 mg IM PLUS azithromycin 2 g orally (single dose) 1
• Ertapenem 1 g IM for 3 days 1
• Note: Most ceftriaxone failures involve pharyngeal sites, not urogenital 1

Partner Management

Evaluation and Treatment Timeline

Evaluate and treat all sex partners from the preceding 60 days 3, 1, 6. If last sexual contact was >60 days before diagnosis, treat the most recent partner 4.

Expedited Partner Therapy

If partners cannot be linked to timely evaluation and treatment, consider expedited partner therapy using cefixime 400 mg PLUS azithromycin 1 g delivered to the partner by the patient, disease investigation specialist, or collaborating pharmacy 3, 1, 6.

Sexual Activity Restrictions

Patients must avoid sexual intercourse until therapy is completed and both patient and partners are asymptomatic 1, 6.

Retesting for Reinfection

Retest all patients 3 months after treatment due to high reinfection rates (most infections at 3 months represent reinfection, not treatment failure) 1, 9, 2. Pregnant women with antenatal gonococcal infection should be retested in the third trimester unless recently treated 9.

Critical Pitfalls to Avoid

Never Use These Regimens

• Fluoroquinolones (ciprofloxacin, ofloxacin) due to widespread resistance, despite historical 99.8% cure rates 3, 1, 2
• Azithromycin 1 g alone (insufficient efficacy at only 93%) 1
• Oral cephalosporins as first-line therapy (cefixime no longer recommended as first-line) 3

Common Errors

• Substituting tablets/capsules for suspension in otitis media treatment (suspension achieves higher peak levels) 10
• Failing to treat for chlamydia concurrently 1, 2
• Using alternative regimens without mandatory test-of-cure 3, 1
• Treating MSM or travelers with anything other than ceftriaxone-based therapy 4, 1

Duration of Therapy for Streptococcus pyogenes Co-infection

If treating pharyngitis/tonsillitis where S. pyogenes is suspected, administer therapeutic dosage for at least 10 days (though data on rheumatic fever prevention with cefixime are unavailable) 10.