What is the recommended treatment for an adult male with uncomplicated genital Chlamydia trachomatis infection and presumed co‑infection with Neisseria gonorrhoeae?

Treatment for Uncomplicated Gonorrhea and Chlamydia Co-infection in Adult Males

For an adult male with uncomplicated genital chlamydia and presumed gonorrhea co-infection, administer ceftriaxone 500 mg intramuscularly as a single dose PLUS azithromycin 1 g orally as a single dose. 1

Primary Recommendation

• Ceftriaxone 500 mg IM (single dose) + Azithromycin 1 g orally (single dose) is the CDC-recommended first-line dual therapy regimen that addresses both gonorrhea and chlamydia simultaneously with optimal efficacy 1
• This regimen achieves a 99.1% cure rate for uncomplicated urogenital and anorectal gonorrhea while providing complete chlamydia coverage in a single administration 1
• Dual therapy is mandatory—never treat gonorrhea without also treating chlamydia, as co-infection occurs in 20-50% of cases 2, 1

Rationale for This Specific Regimen

• Azithromycin 1 g is strongly preferred over doxycycline 100 mg twice daily for 7 days due to single-dose convenience, superior compliance, and substantially higher prevalence of gonococcal resistance to tetracycline than to azithromycin 1
• The combination addresses antimicrobial resistance concerns by using two drugs with different mechanisms of action, potentially delaying emergence of cephalosporin resistance 1
• Ceftriaxone provides sustained bactericidal levels with 98.9% efficacy, superior to all oral alternatives 1

Alternative Regimen (Only When Ceftriaxone Unavailable)

• If ceftriaxone is not available: Cefixime 400 mg orally (single dose) + Azithromycin 1 g orally (single dose) 1
• Mandatory test-of-cure at 1 week is required with the cefixime regimen due to rising cefixime MICs and declining effectiveness (97.4% cure rate vs 99.1% for ceftriaxone) 1, 3
• Cefixime should never be used as monotherapy without azithromycin, as this violates CDC dual therapy recommendations 1

Severe Cephalosporin Allergy

• For patients with documented severe cephalosporin allergy: Azithromycin 2 g orally (single dose) for gonorrhea PLUS doxycycline 100 mg orally twice daily for 7 days for chlamydia 1, 4
• Azithromycin 2 g achieves 98.9% cure rates but has high gastrointestinal side effects (35.3% of patients experience GI symptoms, with 2.9% severe) 5
• Mandatory test-of-cure at 1 week is required for all non-cephalosporin regimens 1, 4
• Alternative: Gentamicin 240 mg IM + Azithromycin 2 g orally achieves 100% cure for urogenital infections, but has poor pharyngeal efficacy (only 80% cure rate) 6, 4

Critical Contraindications

• Never use azithromycin 1 g alone for gonorrhea—it achieves only 93% efficacy and risks rapid resistance emergence 1
• Never use fluoroquinolones (ciprofloxacin, ofloxacin) due to widespread resistance, despite historical 99.8% cure rates 2, 1
• Never use doxycycline alone for gonorrhea—it is insufficient as monotherapy and must be combined with ceftriaxone 1

Partner Management

• Evaluate and treat all sexual partners from the preceding 60 days with the same dual therapy regimen (ceftriaxone 500 mg IM + azithromycin 1 g orally), regardless of symptoms or test results 1, 7
• Partners should receive treatment even if asymptomatic, as gonorrhea transmission rates are high and many infections remain asymptomatic until complications develop 1
• Patients must abstain from all sexual intercourse until therapy is completed and both patient and all partners are asymptomatic 1, 7
• Consider expedited partner therapy with oral combination (cefixime 400 mg + azithromycin 1 g) if partners cannot be linked to timely evaluation 1

Follow-Up Requirements

• Routine test-of-cure is NOT needed for patients treated with the recommended ceftriaxone + azithromycin regimen unless symptoms persist 1, 7
• Retest all patients at 3 months after treatment due to high reinfection risk (10-50% of patients) 1, 4
• If symptoms persist after treatment: obtain culture with antimicrobial susceptibility testing immediately, report to local public health within 24 hours, and consult infectious disease specialist 1
• For suspected treatment failure, recommended salvage regimens include gentamicin 240 mg IM + azithromycin 2 g orally or ertapenem 1 g IM for 3 days 1

Additional Screening

• Screen for syphilis with serology at the time of gonorrhea diagnosis 1
• Co-test for HIV, as gonorrhea facilitates HIV transmission 1

Common Pitfalls to Avoid

• Do not assume oral cephalosporins are equivalent to ceftriaxone—cefixime has documented treatment failures in Europe and is only acceptable when ceftriaxone is unavailable 1
• Do not use patient-delivered partner therapy for men who have sex with men (MSM) due to high risk of undiagnosed coexisting STDs or HIV 1
• Do not skip chlamydia treatment even if testing is negative—presumptive treatment is indicated when gonorrhea is diagnosed due to high co-infection rates 2, 1