What is the recommended management for uncomplicated gonorrhea in an adult patient without known drug allergies?

Management of Uncomplicated Gonorrhea

Treat with ceftriaxone 500 mg intramuscularly as a single dose PLUS azithromycin 1 g orally as a single dose for all uncomplicated gonococcal infections of the cervix, urethra, rectum, and pharynx. 1, 2, 3, 4

Primary Treatment Regimen

Ceftriaxone 500 mg IM (single dose) + Azithromycin 1 g orally (single dose) is the only CDC-recommended first-line regimen for uncomplicated gonorrhea. 1, 2, 3, 4

Rationale for Dual Therapy

• This combination addresses both gonorrhea and presumptive chlamydial co-infection, which occurs in 40-50% of gonorrhea cases. 1, 2, 3
• Dual therapy improves treatment efficacy and potentially delays emergence of cephalosporin resistance. 1
• Azithromycin is preferred over doxycycline for chlamydia coverage due to single-dose convenience and compliance advantages. 1

Efficacy Data

• Ceftriaxone achieves 99.1% cure rate for uncomplicated urogenital and anorectal infections. 5, 1
• This regimen provides 95-100% cure rates across all anatomic sites. 3
• Ceftriaxone has superior efficacy for pharyngeal infections compared to all oral alternatives. 1, 2

Alternative Regimens (Only When Ceftriaxone Unavailable)

Cefixime 400 mg orally (single dose) + Azithromycin 1 g orally (single dose) may be used if ceftriaxone is unavailable. 1, 2, 3

Critical Limitations of Cefixime

• Cefixime achieves only 97.4% overall cure rate and just 78.9% for pharyngeal infections. 1, 6
• Mandatory test-of-cure at 1 week is required with cefixime-based regimens due to declining effectiveness. 1, 2, 3
• Cefixime provides lower and less sustained bactericidal levels than ceftriaxone. 5

Severe Cephalosporin Allergy

Azithromycin 2 g orally (single dose) is the only option for patients with severe cephalosporin allergy. 1, 2

• This regimen has only 93% efficacy and causes significant gastrointestinal side effects. 1, 7
• Mandatory test-of-cure at 1 week is required. 1, 2

Absolutely Contraindicated Regimens

Never Use Fluoroquinolones

Fluoroquinolones (ciprofloxacin, ofloxacin, levofloxacin) are absolutely contraindicated for gonorrhea treatment due to widespread resistance. 1, 2, 3

• Despite historical cure rates of 99.8%, quinolones are no longer effective. 5, 1
• This applies to all patient populations and all anatomic sites. 1

Never Use Azithromycin Monotherapy

Azithromycin 1 g alone should never be used for gonorrhea treatment due to insufficient efficacy (only 93% cure rate) and rapid resistance emergence. 1, 2, 7

Spectinomycin Limitations

• Spectinomycin achieves only 52% cure rate for pharyngeal infections and should be avoided if pharyngeal exposure is suspected. 1, 2
• Spectinomycin 2 g IM may be considered for urogenital infections in severe cephalosporin allergy, but has poor pharyngeal efficacy. 5, 1

Site-Specific Considerations

Pharyngeal Gonorrhea

Pharyngeal gonorrhea is significantly more difficult to eradicate than urogenital or anorectal infections. 1, 2, 3

• Ceftriaxone 500 mg IM is the only reliably effective treatment for pharyngeal infections. 1, 2
• Oral cephalosporins (including cefixime) have markedly reduced efficacy at this site. 1, 2
• Spectinomycin and gentamicin have poor pharyngeal efficacy and should not be used. 1, 2

Gonococcal Conjunctivitis

Ceftriaxone 1 g IM (single dose) plus saline eye lavage is recommended for gonococcal conjunctivitis. 5, 1

Disseminated Gonococcal Infection

• Hospitalization is recommended for initial therapy. 5, 1
• Ceftriaxone 1 g IM or IV every 24 hours until clinical improvement (24-48 hours), then switch to oral therapy to complete 1 week total. 5, 1
• Assess for endocarditis and meningitis. 5, 1

Special Populations

Pregnancy

Pregnant women should receive ceftriaxone 500 mg IM (single dose) + azithromycin 1 g orally (single dose). 1, 2, 3

• Never use quinolones, tetracyclines, or doxycycline in pregnancy due to fetal safety concerns. 5, 1, 2
• If cephalosporin allergy exists, spectinomycin 2 g IM + azithromycin 1 g orally may be used. 5, 1

Men Who Have Sex with Men (MSM)

Ceftriaxone is the only recommended treatment for MSM due to higher prevalence of resistant strains. 1, 3

• Do not use quinolones in this population. 1, 3
• Do not use patient-delivered partner therapy for MSM due to high risk of undiagnosed coexisting STDs or HIV. 1

Patients with Recent Foreign Travel

Ceftriaxone 500 mg IM is the only recommended treatment for patients with history of recent foreign travel due to increased risk of resistant strains. 1

Follow-Up Requirements

Routine Test-of-Cure NOT Required

Patients treated with the recommended ceftriaxone + azithromycin regimen do NOT need routine test-of-cure unless symptoms persist. 1, 2, 3

Mandatory Test-of-Cure Required For:

• All patients receiving cefixime-based regimens (test at 1 week). 1, 2, 3
• All patients receiving azithromycin 2 g monotherapy (test at 1 week). 1, 2
• Any patient with persistent symptoms after treatment. 1, 3

Reinfection Screening

Consider retesting all patients at 3 months after treatment due to high reinfection risk. 1, 2, 3

• Most post-treatment infections represent reinfection rather than treatment failure. 1

Treatment Failure Management

If treatment failure is suspected:

1. Obtain specimens for culture and antimicrobial susceptibility testing immediately from all potentially infected sites. 1, 3
2. Report the case to local public health officials within 24 hours. 1
3. Consult an infectious disease specialist. 1, 3
4. Recommended salvage regimens include:
   • Gentamicin 240 mg IM + azithromycin 2 g orally (single dose) 1
   • Ertapenem 1 g IM for 3 days 1

Partner Management

All sexual partners from the preceding 60 days must be evaluated and treated with the same dual therapy regimen (ceftriaxone 500 mg IM + azithromycin 1 g orally), regardless of symptoms or test results. 1, 2, 3

Expedited Partner Therapy

• Consider expedited partner therapy with oral combination therapy (cefixime 400 mg + azithromycin 1 g) if partners cannot be linked to timely evaluation. 1, 2
• Do NOT use expedited partner therapy for MSM due to high risk of undiagnosed coexisting STDs or HIV. 1

Sexual Activity Restrictions

Patients must abstain from sexual intercourse until therapy is completed and both patient and all partners are asymptomatic. 1, 2, 3

Additional Screening

Screen for syphilis with serology at the time of gonorrhea diagnosis. 1, 3

Perform HIV co-testing given that gonorrhea facilitates HIV transmission. 1, 3

Administration Details

Ceftriaxone Preparation (from FDA Label)

• For IM injection: Reconstitute 500 mg vial with 1.8 mL diluent to achieve 250 mg/mL concentration. 8
• Inject well within the body of a relatively large muscle. 8
• Do not use diluents containing calcium (such as Ringer's solution or Hartmann's solution). 8

Neonatal Considerations

• Ceftriaxone is contraindicated in neonates ≤28 days if they require calcium-containing IV solutions. 8
• Hyperbilirubinemic neonates should not be treated with ceftriaxone. 8
• If ceftriaxone must be used in neonates, administer IV doses over 60 minutes to reduce risk of bilirubin encephalopathy. 8

Critical Pitfalls to Avoid

• Never use cefixime as monotherapy without azithromycin or doxycycline—this violates CDC dual therapy recommendations. 1
• Never assume symptom resolution equals cure when suboptimal regimens were used—test-of-cure is mandatory for cefixime and azithromycin monotherapy. 1
• Never use oral cephalosporins for suspected pharyngeal infections—ceftriaxone IM is required. 1, 2
• Never delay treatment waiting for culture results—gonorrhea transmission rates are high enough to warrant immediate empiric treatment. 1