What are the first-line treatments for gonorrhea and chlamydia?

First-Line Treatment for Gonorrhea and Chlamydia

The current first-line treatment for uncomplicated gonorrhea is ceftriaxone 500 mg intramuscularly as a single dose, plus doxycycline 100 mg orally twice daily for 7 days if chlamydial coinfection has not been excluded. 1, 2

Primary Treatment Regimen

For Gonorrhea

• Ceftriaxone 500 mg IM once is the recommended treatment for uncomplicated urogenital, anorectal, and pharyngeal gonorrhea 1, 2
• This represents an increase from the previous 250 mg dose due to antimicrobial stewardship concerns and rising azithromycin resistance 1, 2
• Ceftriaxone remains highly effective with <0.1% of U.S. isolates showing elevated minimum inhibitory concentrations (>0.25 mcg/mL) 2

For Chlamydia Coinfection

• Add doxycycline 100 mg orally twice daily for 7 days if chlamydial infection has not been excluded 1, 2
• Doxycycline is now preferred over azithromycin as the second agent due to rising azithromycin resistance (nearly 5% of isolates in 2018 had elevated MICs ≥2.0 mcg/mL) 2
• Azithromycin 1 g orally as a single dose remains an acceptable alternative to doxycycline for chlamydia coverage 3

Critical Rationale for Current Recommendations

The shift away from dual therapy with azithromycin reflects several key considerations:

• Antimicrobial stewardship: Routine use of azithromycin when chlamydia is excluded contributes to resistance in commensal organisms 1, 2
• Rising azithromycin resistance: Rapid increase in azithromycin-resistant gonorrhea strains necessitated reevaluation of dual therapy 1, 2
• Stable ceftriaxone susceptibility: U.S. surveillance data show minimal ceftriaxone resistance, supporting monotherapy when chlamydia is excluded 2

Alternative Regimens

When Ceftriaxone is Unavailable

• Cefixime 400 mg orally once PLUS azithromycin 1 g orally once can be used 4, 3
• Mandatory test-of-cure at 1 week is required with this regimen due to inferior efficacy compared to ceftriaxone 5, 3
• Cefixime achieves lower and less sustained bactericidal levels than ceftriaxone 4

For Severe Cephalosporin Allergy

• Gentamicin 240 mg IM once PLUS azithromycin 2 g orally once is an option 3, 6
• However, gentamicin has significantly reduced efficacy for pharyngeal infections (only 80% cure rate vs. 96% for ceftriaxone) 6
• Azithromycin 2 g orally once alone can be used but has only 93% efficacy and causes gastrointestinal side effects in 35% of patients 5, 3, 7
• Test-of-cure at 1 week is mandatory with alternative regimens 5, 3

Site-Specific Considerations

Pharyngeal Gonorrhea

• Pharyngeal infections are significantly more difficult to eradicate than urogenital or anorectal infections 3
• Ceftriaxone 500 mg IM is the only reliably effective treatment for pharyngeal gonorrhea 3
• Gentamicin has poor pharyngeal efficacy (only 80% cure rate) 6
• Spectinomycin has only 52% efficacy for pharyngeal infections and should be avoided 5, 3

Genital Infections

• Gentamicin 240 mg IM plus azithromycin 2 g showed 94% cure rate for genital infections, which may be acceptable when ceftriaxone cannot be used 6

Critical Pitfalls to Avoid

• Never use fluoroquinolones (ciprofloxacin, ofloxacin, levofloxacin) for gonorrhea due to widespread resistance 4, 3
• Never use azithromycin 1 g alone for gonorrhea treatment—it has only 93% efficacy 5, 3
• Never use oral cephalosporins as first-line therapy—CDC no longer recommends cefixime at any dose as first-line treatment 4
• Never substitute tablets/capsules for suspension when treating otitis media in children, as suspension achieves higher peak blood levels 8

Special Populations

Pregnancy

• Ceftriaxone 500 mg IM once is safe and preferred 5, 3
• Never use doxycycline, quinolones, or tetracyclines in pregnancy 9, 5
• For chlamydia coverage, use azithromycin 1 g orally once or amoxicillin 500 mg three times daily for 7 days 5

Men Who Have Sex with Men (MSM)

• Use the same regimen: ceftriaxone 500 mg IM once 3
• Do not use patient-delivered partner therapy due to high risk of undiagnosed coexisting STDs or HIV 3

Partner Management

• Evaluate and treat all sexual partners from the preceding 60 days 5, 3
• Partners should receive the same dual therapy regimen for both gonorrhea and chlamydia 5, 3
• Patients should avoid sexual intercourse until therapy is completed and both patient and partners are asymptomatic 5, 3
• Expedited partner therapy reduces retreatment rates by 45% 10

Follow-Up and Test-of-Cure

• Routine test-of-cure is NOT needed for patients treated with recommended ceftriaxone regimens unless symptoms persist 5, 3
• Mandatory test-of-cure at 1 week is required for patients receiving cefixime or azithromycin monotherapy 5, 3
• Retest all patients approximately 3 months after treatment due to high reinfection risk (10% retreatment rate within 2 years) 5, 10
• If symptoms persist, obtain culture with antimicrobial susceptibility testing 3

Treatment Failure Management

If treatment failure is suspected:

• Obtain specimens for culture and antimicrobial susceptibility testing immediately 3
• Report the case to local public health officials within 24 hours 3
• Consult an infectious disease specialist 3
• Recommended salvage regimens include gentamicin 240 mg IM PLUS azithromycin 2 g orally or ertapenem 1 g IM for 3 days 3