What is the appropriate management for a patient with persistent urethral discharge who received a single 250 mg intramuscular dose of ceftriaxone one month ago and now tests positive for Neisseria gonorrhoeae?

Management of Persistent Gonorrhea After Ceftriaxone Treatment

Immediate Action Required

This patient has documented treatment failure and requires immediate culture with antimicrobial susceptibility testing from all potentially infected sites, followed by re-treatment with ceftriaxone 500 mg IM plus azithromycin 2 g orally as single doses. 1, 2

Critical First Steps

Obtain Cultures Immediately

• Collect specimens from all potentially infected anatomic sites (urethra, pharynx, rectum if indicated) for culture and phenotypic antimicrobial susceptibility testing using disk diffusion, Etest, or agar dilution 2
• Retain the isolate at the laboratory for possible further testing 2
• Report this case to your local or state health department within 24 hours to enable CDC surveillance of emerging resistance patterns 2

Consult Infectious Disease Specialist

• Contact an infectious disease specialist or STD/HIV Prevention Training Center immediately for treatment guidance 2
• Treatment failure with ceftriaxone is extremely rare and represents a potential public health emergency requiring expert consultation 2

Re-Treatment Regimen

Administer ceftriaxone 500 mg IM plus azithromycin 2 g orally, both as single doses, immediately after obtaining cultures. 2

Rationale for This Approach

• The original dose of 250 mg ceftriaxone was likely insufficient; current CDC guidelines recommend 500 mg due to antimicrobial stewardship concerns and evolving resistance patterns 1, 3, 4
• Azithromycin 2 g (rather than 1 g) is used in treatment failure scenarios to maximize efficacy 2
• Ceftriaxone remains the last highly effective antimicrobial for gonorrhea at all anatomic sites, making preservation of its effectiveness critical 2

Mandatory Follow-Up Actions

Test-of-Cure at 1 Week

• Perform test-of-cure exactly 1 week after re-treatment using culture (strongly preferred) or NAAT if culture is unavailable 2
• If NAAT is positive at follow-up, confirm with culture and perform phenotypic antimicrobial susceptibility testing 1

Partner Management

• Evaluate all sexual partners from the preceding 60 days promptly with culture-based diagnosis when possible 2
• Treat partners with the same dual therapy regimen: ceftriaxone 500 mg IM plus azithromycin 1 g orally 1, 3
• If partners cannot be linked to timely evaluation, consider expedited partner therapy using cefixime 400 mg plus azithromycin 1 g orally 2

Additional Screening

• Screen for syphilis with serology at this visit 1, 3
• Perform HIV testing, as gonorrhea facilitates HIV transmission 1

Why Treatment Likely Failed

Possible Explanations to Investigate

Inadequate Initial Dosing

• The patient received 250 mg ceftriaxone, but current CDC guidelines recommend 500 mg due to rising minimum inhibitory concentrations (MICs) 1, 4
• The 250 mg dose was the standard until 2020, when it was increased to 500 mg 4

Pharyngeal Infection

• Pharyngeal gonorrhea is significantly more difficult to eradicate than urogenital or anorectal infections 1, 3
• Most documented ceftriaxone treatment failures involve the pharynx, not urogenital sites 1
• Always obtain pharyngeal cultures in treatment failure cases, even if the patient denies oral sexual contact 1, 3

Reinfection vs. True Treatment Failure

• Most post-treatment positive tests represent reinfection rather than treatment failure 1
• Carefully assess whether the patient had sexual contact with untreated partners during the past month 1
• However, given the one-month interval and persistent symptoms, this case warrants full treatment-failure workup regardless 2

Antimicrobial Resistance

• While ceftriaxone resistance remains extremely rare in the United States, rising MICs have been documented 1, 4
• This is why culture with susceptibility testing is absolutely mandatory in this scenario 2

Critical Pitfalls to Avoid

Never Use These Agents

• Fluoroquinolones (ciprofloxacin, ofloxacin, levofloxacin) are completely contraindicated due to widespread resistance, despite historic cure rates >99% 1, 3, 2
• Azithromycin 1 g as monotherapy has only 93% efficacy and promotes rapid resistance development 1, 3, 2
• Cefixime as first-line therapy has rising MICs, declining effectiveness (only 97.4% cure rate vs. 99.1% for ceftriaxone), and particularly poor efficacy for pharyngeal infections (only 78.9% cure rate) 1, 2, 5, 6
• Spectinomycin has only 52% efficacy for pharyngeal infections and should be avoided when pharyngeal exposure is possible 1, 3

Do Not Delay Treatment

• Administer re-treatment immediately after obtaining cultures—do not wait for susceptibility results 2
• Delayed treatment increases risk of complications (pelvic inflammatory disease, epididymitis) and ongoing transmission 4

Sexual Activity Restrictions

• The patient must abstain from all sexual intercourse until:
  • Re-treatment is completed AND
  • Test-of-cure is negative AND
  • All partners have been treated and are asymptomatic 1, 3

Special Considerations

If Severe Cephalosporin Allergy Exists

• Use azithromycin 2 g orally as a single dose 2
• Mandatory test-of-cure at 1 week is required with this alternative regimen 2
• This regimen has lower efficacy (approximately 93%) and high gastrointestinal side effects 1

If Patient Is Pregnant

• Use the standard re-treatment regimen: ceftriaxone 500 mg IM plus azithromycin 2 g orally 3
• Never use quinolones, tetracyclines, or doxycycline in pregnancy 1, 3

If Patient Is MSM

• Men who have sex with men have higher prevalence of resistant strains 1, 3
• Ceftriaxone is the only acceptable treatment; never use quinolones in this population 1, 3
• Do not offer expedited partner therapy to MSM partners due to high risk of undiagnosed coexisting STDs or HIV 1

Documentation and Reporting

• Document the treatment failure in the medical record with detailed antimicrobial history 2
• Report to local/state health department within 24 hours to enable CDC surveillance 2
• Maintain communication with the laboratory to ensure isolate retention and susceptibility testing completion 2