What is the recommended treatment for Chlamydia trachomatis and Neisseria gonorrhoeae?

Treatment for Chlamydia trachomatis and Neisseria gonorrhoeae

For uncomplicated urogenital, anorectal, and pharyngeal gonorrhea with presumptive chlamydia coverage, treat with ceftriaxone 500 mg IM once PLUS doxycycline 100 mg orally twice daily for 7 days if chlamydial coinfection has not been excluded. 1, 2

Primary Treatment Regimen

The current CDC recommendation represents a shift from previous dual therapy with azithromycin due to rising azithromycin resistance (nearly 5% of isolates with elevated MICs by 2018) while ceftriaxone MICs have remained stable with <0.1% showing alert values. 1, 2

• Ceftriaxone 500 mg IM as a single dose treats gonorrhea at all anatomic sites (cervix, urethra, rectum, pharynx) 1, 2, 3
• Add doxycycline 100 mg orally twice daily for 7 days if chlamydial infection has not been excluded 1, 2, 3
• This regimen achieves 99.1% cure rate for uncomplicated urogenital and anorectal gonorrhea 4
• Doxycycline is now preferred over azithromycin 1 g for chlamydia coverage due to antimicrobial stewardship concerns and rising azithromycin resistance 1, 2

Alternative Regimens When Ceftriaxone Unavailable

If ceftriaxone is not available, use cefixime 400 mg orally once PLUS azithromycin 1 g orally once, with mandatory test-of-cure at 1 week. 4

Special Populations

Pregnancy

• Use ceftriaxone 500 mg IM once PLUS azithromycin 1 g orally once 4
• Never use quinolones, tetracyclines, or doxycycline in pregnancy 5, 4
• Pregnant patients require test-of-cure 4 weeks after treatment 3

Severe Cephalosporin Allergy

• Azithromycin 2 g orally once is the only option, but has lower efficacy (93% cure rate) and high gastrointestinal side effects (35.3% of patients, with 2.9% severe) 4, 6
• Mandatory test-of-cure at 1 week is required 4
• Critical limitation: No recommended alternative exists for pharyngeal gonorrhea in patients with cephalosporin allergy 2

Men Who Have Sex with Men (MSM)

• Must use ceftriaxone-based regimen; never use quinolones due to higher prevalence of resistant strains 5, 4
• Screen at least annually 3

Site-Specific Considerations

Pharyngeal gonorrhea is significantly more difficult to eradicate than urogenital or anorectal infections. 4, 2

• Ceftriaxone 500 mg IM is the only reliably effective treatment for pharyngeal infections 4
• Spectinomycin has only 52% efficacy for pharyngeal infections and should be avoided 5, 4
• Gentamicin has only 20% cure rate for pharyngeal infections 4

Critical Pitfalls to Avoid

• Never use quinolones (ciprofloxacin, ofloxacin) for gonorrhea treatment due to widespread resistance, despite their historical 99.8% cure rate 4, 1
• Never use azithromycin 1 g alone for gonorrhea due to insufficient efficacy (only 93% cure rate) 4, 6
• Never use tetracyclines as sole therapy for gonococcal infection due to resistance 7
• Do not use patient-delivered partner therapy for MSM due to high risk of undiagnosed coexisting STDs or HIV 4

Partner Management

• Evaluate and treat all sexual partners from the preceding 60 days for both N. gonorrhoeae and C. trachomatis 5, 4
• Partners should receive the same dual therapy regimen 4
• Patients must avoid sexual intercourse until therapy is completed and both patient and partners are asymptomatic 5, 4
• Consider expedited partner therapy with oral combination therapy (cefixime 400 mg plus azithromycin 1 g) if partners cannot be linked to timely evaluation 4

Follow-Up Requirements

• Patients treated with recommended regimens do not need routine test-of-cure unless symptoms persist 5, 1
• Mandatory test-of-cure at 1 week is required for patients receiving cefixime or azithromycin monotherapy 4
• If symptoms persist after treatment, obtain culture with antimicrobial susceptibility testing immediately 5, 4
• Retest all nonpregnant patients approximately 3 months after treatment or at first visit within 12 months due to high reinfection rates (up to 40-50% coinfection rate) 5, 4, 3
• If nucleic acid amplification testing is positive at follow-up, confirm with culture and perform phenotypic antimicrobial susceptibility testing 4

Treatment Failure Management

If treatment failure is suspected:

• Obtain specimens for culture and antimicrobial susceptibility testing immediately 4, 2
• Report the case to local public health officials within 24 hours 4
• Consult an infectious disease specialist 4
• Recommended salvage regimens include gentamicin 240 mg IM PLUS azithromycin 2 g orally, or ertapenem 1 g IM for 3 days 4
• Most ceftriaxone treatment failures involve pharyngeal sites, not urogenital sites 4

Rationale for Current Recommendations

The shift from dual therapy with azithromycin to doxycycline reflects:

• Rising azithromycin resistance (nearly 5% of isolates with elevated MICs ≥2.0 mcg/mL by 2018) 2
• Stable ceftriaxone MICs with <0.1% exhibiting alert values (>0.25 mcg/mL) 2
• Antimicrobial stewardship concerns about impact on commensal organisms 1, 2
• Extremely high coinfection rates (40-50% of gonorrhea patients also have chlamydia) necessitate presumptive treatment for both organisms when empiric therapy is indicated 4