How should I treat an adult with co‑infection of gonorrhea and chlamydia?

Treatment of Gonorrhea and Chlamydia Co-Infection

For adults with gonorrhea and chlamydia co-infection, administer ceftriaxone 500 mg intramuscularly as a single dose PLUS doxycycline 100 mg orally twice daily for 7 days. 1, 2

Primary Treatment Regimen

• Ceftriaxone 500 mg IM single dose is the cornerstone of therapy, achieving a 99.1% cure rate for uncomplicated urogenital and anorectal gonorrhea. 1
• Doxycycline 100 mg orally twice daily for 7 days is the preferred chlamydia treatment component, providing superior efficacy compared to single-dose azithromycin for chlamydial infections. 1, 3, 4
• This regimen addresses both pathogens simultaneously, which is critical because 20-50% of gonorrhea cases involve chlamydial co-infection. 1

Why This Specific Combination

The 2020 CDC update moved away from the previous ceftriaxone-azithromycin dual therapy for several key reasons:

• Antimicrobial stewardship concerns about azithromycin's impact on commensal organisms and concurrent pathogens, combined with increasing azithromycin resistance in gonorrhea. 2
• Doxycycline provides more reliable chlamydia coverage with a 7-day course, eliminating concerns about treatment failure from single-dose therapy. 3, 4
• Ceftriaxone resistance remains extremely low in surveillance data, making monotherapy for gonorrhea acceptable when chlamydia is definitively treated. 2

Alternative Regimens (When Ceftriaxone Unavailable)

• Cefixime 400 mg orally single dose PLUS doxycycline 100 mg orally twice daily for 7 days can be used if ceftriaxone is not available. 1
• Mandatory test-of-cure at 1 week is required with cefixime-based regimens due to lower cure rates (97.4% vs 99.1% for ceftriaxone) and rising minimum inhibitory concentrations. 1, 5
• Cefixime has particularly poor efficacy for pharyngeal gonorrhea (only 78.9% cure rate), making it unsuitable for pharyngeal infections. 1

Severe Cephalosporin Allergy

• Azithromycin 2 g orally single dose is the only option for patients who cannot receive cephalosporins, but has lower efficacy (93% for gonorrhea) and high gastrointestinal side effects (35.3% of patients). 1, 6
• Mandatory test-of-cure at 1 week is required with azithromycin monotherapy. 1
• This regimen treats both gonorrhea and chlamydia simultaneously but is significantly inferior to ceftriaxone-based therapy. 6

Critical Medications to Avoid

• Never use fluoroquinolones (ciprofloxacin, ofloxacin, levofloxacin) for gonorrhea treatment due to widespread resistance, despite historical cure rates of 99.8%. 1, 7
• Never use azithromycin 1 g alone for gonorrhea—it has only 93% efficacy and risks rapid resistance emergence. 1
• Never use cefixime for pharyngeal gonorrhea as first-line therapy due to poor efficacy at this site. 1

Site-Specific Considerations

• Pharyngeal gonorrhea requires ceftriaxone 500 mg IM—oral cephalosporins are unreliable for this anatomic site. 1
• Pharyngeal infections are significantly more difficult to eradicate than urogenital or anorectal infections. 1, 7
• If pharyngeal infection is suspected or confirmed, ceftriaxone is mandatory; cefixime should not be used. 1

Special Populations

Pregnancy

• Use ceftriaxone 500 mg IM single dose PLUS azithromycin 1 g orally single dose in pregnant patients. 1
• Never use doxycycline, quinolones, or tetracyclines during pregnancy due to fetal safety concerns. 1, 3
• Azithromycin 1 g single dose is the only acceptable chlamydia treatment in pregnancy (amoxicillin 500 mg three times daily for 7 days is an alternative). 1

Men Who Have Sex with Men (MSM)

• Ceftriaxone is the only recommended treatment for MSM due to higher prevalence of resistant strains. 1
• Do not use quinolones in this population. 1
• Do not offer expedited partner therapy to MSM due to high risk of undiagnosed co-existing STDs or HIV. 1

Partner Management

• Evaluate and treat all sexual partners from the preceding 60 days with the same dual therapy regimen (ceftriaxone 500 mg IM plus doxycycline 100 mg twice daily for 7 days), regardless of symptoms or test results. 1
• If partners cannot be linked to timely evaluation, consider expedited partner therapy with cefixime 400 mg plus azithromycin 1 g orally (not recommended for MSM). 1
• Patients must abstain from sexual intercourse until therapy is completed and both they and all partners are asymptomatic. 1

Follow-Up Requirements

• Routine test-of-cure is NOT required after ceftriaxone-based regimens unless symptoms persist. 1, 2
• Test-of-cure IS mandatory at 1 week for patients treated with cefixime or azithromycin monotherapy. 1
• Consider retesting all patients at 3 months due to high reinfection risk (most post-treatment infections represent reinfection, not treatment failure). 1
• If symptoms persist after treatment, obtain culture with antimicrobial susceptibility testing and report to local public health officials within 24 hours. 1

Common Pitfalls to Avoid

• Do not omit chlamydia treatment even when chlamydia testing is negative at the time of gonorrhea diagnosis—presumptive treatment is essential due to high co-infection rates. 1
• Do not use single-dose azithromycin 1 g as the chlamydia component when treating co-infection; doxycycline 7-day course is preferred for reliability. 4, 2
• Do not assume oral cephalosporins are equivalent to ceftriaxone—cefixime has lower bactericidal levels and reduced efficacy, particularly for pharyngeal infections. 1, 5
• Do not use spectinomycin for pharyngeal gonorrhea—it has only 52% efficacy at this site. 1