What is the recommended diagnosis and management approach for a sexually active patient with suspected gonorrhea, including treatment options and considerations for potential co-infections and antibiotic resistance?

Gonococcal Diagnosis and Management

Diagnostic Approach

For sexually active patients with suspected gonorrhea, use nucleic acid amplification tests (NAATs) as the preferred diagnostic method due to their superior sensitivity and specificity, and test all patients simultaneously for chlamydia, syphilis, and HIV. 1

Specimen Collection for Diagnosis

• NAATs are FDA-cleared for endocervical swabs, vaginal swabs (provider or self-collected), male urethral swabs, and urine specimens from both males and females, offering the widest range of testing options 1
• Urine NAAT testing has comparable sensitivity and specificity to cervical and urethral samples, making it a convenient option for urogenital screening 2
• For pharyngeal and rectal sites, culture remains the standard because NAATs are not FDA-cleared for these sites and may cross-react with nongonococcal Neisseria species in the throat 1
• Pharyngeal screening is particularly important in adolescents where these infections are common 3

When to Obtain Culture

• Culture with antimicrobial susceptibility testing is mandatory for treatment failures to guide subsequent therapy and monitor resistance patterns 1
• Maintain culture capacity even with widespread NAAT use to preserve antimicrobial resistance surveillance capabilities 1
• Gram stain of endocervical, pharyngeal, or rectal specimens is insufficient and not recommended for diagnosis 1

Treatment Recommendations

The first-line treatment for uncomplicated urogenital, anorectal, or pharyngeal gonorrhea is ceftriaxone 250 mg intramuscularly as a single dose PLUS azithromycin 1 g orally as a single dose. 1

Primary Treatment Regimen

• Ceftriaxone 250 mg IM single dose is more effective than the previously recommended 125 mg dose, particularly for pharyngeal infections 1, 2
• Azithromycin 1 g orally is strongly preferred over doxycycline 100 mg twice daily for 7 days as the second antimicrobial due to high tetracycline resistance rates among gonococcal isolates 1
• Dual therapy addresses both gonorrhea and presumptive chlamydia co-infection while potentially slowing antimicrobial resistance development 1

Alternative Regimens

If ceftriaxone is unavailable:

• Cefixime 400 mg orally single dose PLUS azithromycin 1 g orally single dose (or doxycycline 100 mg twice daily for 7 days) 1
• Requires test-of-cure in 1 week at the infected anatomic site 1

If severe cephalosporin allergy:

• Azithromycin 2 g orally as a single dose 1
• Requires test-of-cure in 1 week and should be used sparingly due to resistance concerns 1, 2

Critical Treatment Considerations

• Quinolones (ciprofloxacin, ofloxacin, levofloxacin) are no longer recommended due to widespread resistance 1, 2, 4
• Do not use quinolones in men who have sex with men, patients with recent foreign travel, or infections acquired in areas with high resistance 1
• Medications should be dispensed on-site to maximize compliance 1

Management of Co-Infections

All patients with gonorrhea must be treated presumptively for chlamydia unless a negative NAAT result is available at the time of treatment. 1

Chlamydia Co-Treatment Decision Algorithm

• If chlamydial NAAT is negative at time of gonorrhea treatment: No additional chlamydia treatment needed 1
• If chlamydial test results unavailable or non-NAAT test was used: Treat for both gonorrhea and chlamydia 1
• Co-infection rates are extremely high, making dual coverage essential in most clinical scenarios 5, 4

Additional STI Testing

• Test all gonorrhea patients for syphilis and HIV at the time of diagnosis 1, 5
• Evaluate for bacterial vaginosis and trichomoniasis in women with cervicitis 1
• In women with >10 WBCs in vaginal fluid without trichomoniasis, this suggests endocervical inflammation from gonorrhea or chlamydia 1

Partner Management

All sexual partners within the preceding 60 days of symptom onset or diagnosis must be evaluated and treated empirically for both gonorrhea and chlamydia before test results are available. 1, 5

Partner Notification Timeline

• If last sexual contact was >60 days before diagnosis, the most recent sex partner should still be treated 1, 5
• Partners should receive the same dual therapy regimen (ceftriaxone 250 mg IM plus azithromycin 1 g orally) 5

Expedited Partner Therapy

• For heterosexual partners who cannot access timely evaluation, expedited partner therapy with oral cefixime 400 mg plus azithromycin 1 g may be delivered by the patient, disease investigation specialist, or collaborating pharmacy 1
• Do NOT use expedited partner therapy in men who have sex with men due to high risk of coexisting undiagnosed STDs or HIV requiring in-person evaluation 5
• Female partners require education about seeking medical evaluation for possible pelvic inflammatory disease, especially if symptomatic 5

Abstinence Requirements

• Both patient and partners must abstain from sexual intercourse until 7 days after therapy initiation and complete symptom resolution to prevent reinfection 1, 5

Follow-Up and Test-of-Cure

Routine test-of-cure is not required for patients treated with recommended first-line therapy, but retesting in 3-6 months is essential due to high reinfection rates. 2

When Test-of-Cure IS Required

• Treatment with alternative regimens (cefixime or azithromycin monotherapy): Test at 1 week 1
• Persistent symptoms after treatment: Perform culture with antimicrobial susceptibility testing 1
• Pharyngeal infections treated with alternative regimens: Test-of-cure is particularly important 1

Test-of-Cure Methodology

• Culture is ideal for test-of-cure, but NAAT may be used if culture unavailable 1
• If NAAT is positive on test-of-cure, confirm with culture and perform antimicrobial susceptibility testing 1

Treatment Failure Management

For persistent infection after recommended dual therapy, obtain culture with antimicrobial susceptibility testing, consult infectious disease specialist, and report to CDC through local/state health department within 24 hours. 1

Treatment Failure Protocol

• Re-treat with ceftriaxone 250 mg IM single dose PLUS azithromycin 2 g orally single dose 1
• Perform test-of-cure 1 week after re-treatment 1
• Ensure partners from preceding 60 days are evaluated with culture and treated appropriately 1
• Laboratory must retain isolate for possible further testing 1

Special Populations

Neonates

• Ceftriaxone is contraindicated in premature neonates and in neonates ≤28 days requiring calcium-containing IV solutions due to precipitation risk 6
• If ceftriaxone must be used in neonates, administer IV over 60 minutes to reduce risk of bilirubin encephalopathy 6
• Hyperbilirubinemic neonates should not be treated with ceftriaxone 6

HIV-Infected Patients

• Use the same treatment regimen as HIV-negative patients 1
• Treatment is vital in HIV-infected women because cervicitis increases cervical HIV shedding and transmission risk 1

Pregnant Women

• No dosage adjustment necessary for standard ceftriaxone-azithromycin regimen 6

Screening Recommendations

Screen all sexually active women at increased risk annually, including all women <25 years and older women with risk factors. 3

Risk Factors for Screening

• Age <25 years (universal screening) 3
• Previous gonorrhea infection 3
• Presence of other STDs 3
• New or multiple sex partners 3
• Inconsistent condom use 3
• Commercial sex work 3
• Drug use 3
• HIV infection with sexual activity or pregnancy 3

Common Pitfalls to Avoid

• Never use quinolones for gonorrhea treatment regardless of local susceptibility data, as resistance is widespread and increasing 1, 2, 4
• Do not rely on ceftriaxone alone without addressing chlamydia co-infection 1, 5
• Do not use calcium-containing diluents (Ringer's solution, Hartmann's solution) with ceftriaxone due to precipitation risk 6
• Do not assume negative microscopy rules out infection—NAATs are far more sensitive 1, 2
• Reinfection is the primary cause of treatment failure, not antimicrobial resistance, emphasizing the critical importance of partner treatment 5