What is the recommended management for a patient with gonococcal urethritis?

Management of Gonococcal Urethritis

The recommended first-line treatment for gonococcal urethritis is ceftriaxone 1 g intramuscularly (or intravenously) as a single dose plus azithromycin 1 g orally as a single dose. 1, 2

Diagnostic Approach

Before initiating treatment, confirm the diagnosis through:

• Gram stain of urethral discharge showing intracellular gram-negative diplococci for rapid preliminary diagnosis 1
• Nucleic acid amplification test (NAAT) on first-void urine or urethral swab to confirm gonococcal and chlamydial infection 1
• Urethral swab culture before treatment initiation in NAAT-positive cases to assess antimicrobial resistance profiles 1

In patients with mild symptoms, delaying treatment until NAAT results are available allows for pathogen-directed therapy and reduces unnecessary antibiotic exposure 1.

Primary Treatment Regimen

The current standard of care consists of:

• Ceftriaxone 1 g intramuscularly or intravenously as a single dose 1, 2, 3
• Plus azithromycin 1 g orally as a single dose 1, 2

This dual therapy addresses both gonorrhea and potential chlamydial coinfection 1, 2. The 2020 CDC update increased the ceftriaxone dose from 250 mg to 500 mg (with some guidelines recommending 1 g) due to evolving resistance patterns 3. The European guidelines recommend 1 g as the standard dose 1.

Alternative Regimens

For Patients Unable to Receive Ceftriaxone

Oral alternative (less effective):

• Cefixime 400 mg orally single dose plus azithromycin 1 g orally single dose with mandatory test-of-cure in 1 week 2, 4
• This regimen is less effective due to declining cefixime susceptibility and rising minimum inhibitory concentrations 2

For severe cephalosporin allergy:

• Azithromycin 2 g orally as a single dose (not 1 g, which has only 93% efficacy) with mandatory test-of-cure at 1 week 2, 4, 5
• This achieves approximately 96-99% cure rates but causes significant gastrointestinal distress 2, 4
• Spectinomycin 2 g intramuscularly single dose with 96.7% cure rate for urogenital infections, though availability is limited 2, 4

Regimens for Pharyngeal Gonorrhea

Pharyngeal infections are more difficult to eradicate and require:

• Ceftriaxone 1 g intramuscularly or intravenously (quinolones and spectinomycin are unreliable for pharyngeal sites) 1

Critical Management Components

Partner Management

• All sexual partners from the preceding 60 days must be evaluated and treated for both gonorrhea and chlamydia, regardless of symptoms 2, 4, 5
• Treatment should occur even if partners are asymptomatic 1
• Partner treatment failure is the primary cause of apparent treatment failure 4

Sexual Abstinence

• Patients and all partners must abstain from sexual intercourse until therapy is completed (7 days after single-dose therapy) and symptoms have resolved in both parties 1, 2, 4

Test-of-Cure Requirements

• Routine test-of-cure is NOT necessary for patients treated with recommended ceftriaxone-based regimens who become asymptomatic 2
• Test-of-cure IS mandatory when using alternative regimens (cefixime, azithromycin monotherapy) at 1 week post-treatment 2, 4
• Test-of-cure should use culture (preferred) or NAAT if culture unavailable 5

Special Populations

Pregnant Women

• Use the same ceftriaxone dose (500 mg to 1 g intramuscularly) as non-pregnant patients 2, 4
• Absolutely avoid quinolones and tetracyclines during pregnancy 1, 2, 4
• For chlamydial coverage, use azithromycin instead of doxycycline 1

HIV-Infected Patients

• Use identical treatment regimens as HIV-negative patients 1, 2, 4
• Treatment is particularly vital because gonococcal urethritis increases HIV shedding and transmission risk 2, 4

Critical Pitfalls to Avoid

Quinolone Resistance

• Do NOT use quinolones (ciprofloxacin, ofloxacin, levofloxacin) as first-line therapy due to widespread resistance 1, 2, 5
• While older guidelines (2002-2006) recommended quinolones, resistance rates have rendered them unreliable in most geographic areas 1
• Quinolones should not be used for men who have sex with men, patients with recent foreign travel, or infections acquired in areas with known high resistance 1

Inadequate Azithromycin Dosing

• Never use azithromycin 1 g as monotherapy—it cures only 93% of infections 2, 4, 5
• If azithromycin monotherapy is necessary due to cephalosporin allergy, the dose must be 2 g (not split), despite gastrointestinal side effects 2, 4, 5
• Azithromycin resistance is increasing, with remarkable increases in strains with MIC ≥1 mg/L noted in surveillance studies 6

Cefixime Limitations

• Never use cefixime as first-line due to rising MICs and limited efficacy for pharyngeal infections 5
• Cefixime provides lower and less sustained bactericidal levels than ceftriaxone 1

Management of Treatment Failure

If symptoms persist after recommended treatment:

1. Obtain culture specimens immediately from all infected anatomic sites and perform antimicrobial susceptibility testing 5
2. Retain the isolate at the laboratory for possible further testing 5
3. Report the case to CDC through local or state health department within 24 hours 5
4. Consult an infectious disease specialist immediately for treatment guidance 5

Re-Treatment Regimen for Resistant Cases

• Ceftriaxone 500 mg intramuscularly plus azithromycin 2 g orally, both as single doses 5
• Conduct test-of-cure 1 week after re-treatment using culture (preferred) or NAAT 5
• Evaluate all sex partners from the preceding 60 days with culture and treat as indicated 5

Concurrent Chlamydial Coverage

If chlamydial infection has not been excluded:

• Doxycycline 100 mg orally twice daily for 7 days is the preferred concurrent treatment 1, 3
• This represents a shift from the previous recommendation of azithromycin 1 g for chlamydial coverage, reflecting antimicrobial stewardship concerns 3
• Alternatively, azithromycin 1 g orally single dose can be used if already included in the gonorrhea regimen 1

Surveillance and Follow-Up

• Patients treated with recommended regimens who become asymptomatic do not require routine follow-up cultures 1
• Patients should be instructed to return if symptoms persist or recur after completion of therapy 1
• Symptoms alone, without objective signs of urethritis, are not sufficient basis for re-treatment 1
• All patients diagnosed with gonorrhea should receive testing for other STDs, including syphilis and HIV 1