What is the recommended first‑line therapy for an adult with co‑existing Chlamydia trachomatis and Neisseria gonorrhoeae infection, including guidance for pregnancy, patients weighing >150 kg, doxycycline allergy, and partner treatment?

Treatment of Co-existing Chlamydia and Gonorrhea

For adults with confirmed or suspected co-infection of Chlamydia trachomatis and Neisseria gonorrhoeae, administer ceftriaxone 500 mg intramuscularly as a single dose PLUS doxycycline 100 mg orally twice daily for 7 days. 1, 2

First-Line Dual Therapy Regimen

• Ceftriaxone 500 mg IM single dose achieves 99.1% cure rates for uncomplicated urogenital, anorectal, and pharyngeal gonorrhea 1, 2
• Doxycycline 100 mg orally twice daily for 7 days provides 95-98% cure rates for chlamydia and demonstrates superior efficacy (94-100%) compared to azithromycin (76-87%) for rectal infections 1, 2
• This combination addresses both pathogens simultaneously, given that 20-50% of gonorrhea cases involve chlamydial co-infection 2

Rationale for This Specific Combination

• Dual therapy improves treatment efficacy and potentially delays emergence of cephalosporin resistance in gonorrhea 2
• Doxycycline is preferred over azithromycin for chlamydia treatment when compliance can be ensured, due to superior efficacy for rectal infections 1
• Ceftriaxone remains the only reliably effective agent for pharyngeal gonorrhea, with oral alternatives achieving only 78.9% cure rates 2

Special Population Modifications

Pregnancy

Pregnant patients must receive ceftriaxone 500 mg IM single dose PLUS azithromycin 1 g orally single dose. 1, 2, 3

• Doxycycline, all tetracyclines, and fluoroquinolones are absolutely contraindicated in pregnancy due to fetal safety concerns 1, 2, 3
• Alternative chlamydia option: amoxicillin 500 mg orally three times daily for 7 days 1
• Mandatory test-of-cure at 3-4 weeks post-treatment is required for all pregnant patients, preferably by culture 1
• Retest in third trimester if treated earlier in pregnancy 3

Patients Weighing >150 kg (>331 lb)

• Increase ceftriaxone dose to 1 gram IM for patients weighing >150 kg 4
• Continue standard doxycycline dosing (100 mg twice daily for 7 days) 1

Doxycycline Allergy or Intolerance

If doxycycline cannot be used, substitute azithromycin 1 g orally single dose for the chlamydia component. 1, 2

• Azithromycin 1 g achieves 97% cure rates for genital chlamydia 1
• Single-dose therapy ensures compliance when adherence to 7-day regimens is uncertain 1
• Note: Azithromycin has inferior efficacy (76-87%) compared to doxycycline (94-100%) for rectal chlamydia 1

Severe Cephalosporin Allergy

For documented severe cephalosporin allergy, use gentamicin 240 mg IM single dose PLUS azithromycin 2 g orally single dose. 2

• This regimen achieved 100% cure rates in clinical trials 2
• Mandatory test-of-cure at 1 week is required 2
• Azithromycin 2 g monotherapy should be avoided due to only 93% efficacy and high gastrointestinal side effects 2
• In pregnancy with severe cephalosporin allergy: spectinomycin 2 g IM plus azithromycin 1 g orally 2

Alternative Regimen When Ceftriaxone Unavailable

If ceftriaxone cannot be obtained, use cefixime 400 mg orally single dose PLUS doxycycline 100 mg orally twice daily for 7 days. 1, 2

• Cefixime achieves only 97.4% overall cure rate (vs. 99.1% for ceftriaxone) and 78.9% for pharyngeal infections 2
• Mandatory test-of-cure at 1 week is required with this regimen 2
• This is explicitly a second-line option due to inferior efficacy 2

Partner Management

All sexual partners from the preceding 60 days must be evaluated, tested, and treated empirically with the same dual therapy regimen, regardless of symptoms or test results. 1, 2

• If the most recent sexual contact occurred >60 days before diagnosis, treat the most recent partner 1, 2
• Partners should receive ceftriaxone 500 mg IM plus doxycycline 100 mg twice daily for 7 days (or azithromycin 1 g if pregnant) 1, 2
• Expedited partner therapy with oral cefixime 400 mg plus azithromycin 1 g may be considered when partners cannot access timely evaluation 2
• Do NOT use expedited partner therapy for men who have sex with men due to high risk of undiagnosed co-existing STDs or HIV 2

Sexual Activity Restrictions

• Patients must abstain from all sexual intercourse for 7 days after initiating treatment and until all sex partners have completed treatment and both patient and partners are asymptomatic 1, 2

Follow-Up and Testing Recommendations

Test-of-Cure

• NOT recommended for non-pregnant patients treated with recommended regimens (ceftriaxone plus doxycycline or azithromycin) unless symptoms persist or reinfection is suspected 1, 2
• Testing before 3 weeks post-treatment may yield false-positive results from residual nucleic acids 1
• Required for pregnant patients at 3-4 weeks post-treatment 1
• Required for patients treated with alternative regimens (cefixime-based or gentamicin-based) at 1 week 2

Reinfection Screening

• All women should be retested approximately 3 months after treatment to screen for reinfection, which occurs in up to 39% of cases and increases risk of pelvic inflammatory disease 1
• Consider retesting all patients at 3 months or at next clinical visit within 12 months, regardless of whether partners were reportedly treated 1, 2, 3

Additional STI Testing at Initial Visit

• Test for syphilis by serology 1, 2
• Test for HIV 1, 2
• Consider HPV vaccination referral if age-appropriate 1

Critical Pitfalls to Avoid

• Never use fluoroquinolones (ciprofloxacin, ofloxacin, levofloxacin) for gonorrhea treatment due to widespread resistance, despite historical 99.8% cure rates 1, 2
• Never use azithromycin 1 g alone for gonorrhea treatment—it achieves only 93% efficacy and promotes rapid resistance 2
• Never use doxycycline, tetracyclines, or fluoroquinolones in pregnancy 1, 2, 3
• Never omit chlamydia treatment when gonorrhea is confirmed, even if chlamydia testing is negative, due to 20-50% co-infection rates 2
• Do not wait for test results before treating sexual partners—empiric treatment is essential 1, 2
• Do not assume oral cephalosporins are equivalent to ceftriaxone—they have markedly inferior efficacy, especially for pharyngeal infections 2

Site-Specific Considerations

• Pharyngeal gonorrhea is significantly more difficult to eradicate; ceftriaxone 500 mg IM is the only reliably effective treatment 2
• Rectal chlamydia responds better to doxycycline (94-100% cure) than azithromycin (76-87% cure) 1
• For gonococcal conjunctivitis, use ceftriaxone 1 g IM single dose plus saline eye lavage 2

Treatment Failure Management

• If symptoms persist after completing recommended therapy, obtain cultures with antimicrobial susceptibility testing from all potentially infected sites 2
• Report suspected ceftriaxone treatment failure to local public health officials within 24 hours 2
• Consult infectious disease specialist for treatment failures 2
• Most post-treatment positive tests represent reinfection rather than true treatment failure 2