What is the recommended single dose empiric therapy regimen for Gonorrhea (GC) and Chlamydia?

Single-Dose Empiric Therapy for Gonorrhea and Chlamydia

The recommended single-dose empiric therapy is ceftriaxone 500 mg IM PLUS azithromycin 1 g orally, both given as single doses, to cover both gonorrhea and chlamydia simultaneously. 1, 2, 3

Primary Recommendation

• Ceftriaxone 500 mg IM (single dose) PLUS azithromycin 1 g orally (single dose) is the preferred regimen for empiric treatment when both gonorrhea and chlamydia exposure is suspected 1, 2, 3

• This dual therapy approach is essential because co-infection rates are extremely high, with 40-50% of gonorrhea patients also having chlamydia 1, 2

• The CDC updated the ceftriaxone dose from 250 mg to 500 mg in 2020 due to antimicrobial resistance concerns 3

Critical Limitation: Not Truly Single-Dose for Chlamydia

• Important caveat: While this regimen uses single doses of each drug, azithromycin 1 g as a single dose is the only true single-dose option for chlamydia coverage 1, 2

• If azithromycin cannot be used, doxycycline 100 mg orally twice daily for 7 days is required for adequate chlamydia treatment, which is NOT a single-dose regimen 1, 3

• The CDC now recommends doxycycline over azithromycin for chlamydia when dual therapy is used, due to antimicrobial stewardship concerns and rising azithromycin resistance 3

Alternative Single-Dose Regimens (When Ceftriaxone Unavailable)

• Cefixime 400 mg orally (single dose) PLUS azithromycin 1 g orally (single dose) can be used if ceftriaxone is unavailable 1, 2

  • However, this regimen requires mandatory test-of-cure at 1 week due to inferior efficacy compared to ceftriaxone 1, 2
  • Cefixime has declining effectiveness with cure rates of only 96-98% versus 98-99% for ceftriaxone 4, 5

• Azithromycin 2 g orally (single dose alone) is an option for severe cephalosporin allergy 1, 2

  • This has lower efficacy (only 93%) and causes gastrointestinal side effects in 35% of patients 1, 6
  • Mandatory test-of-cure at 1 week is required 1, 2

Site-Specific Considerations

• Pharyngeal gonorrhea is significantly more difficult to eradicate than urogenital or anorectal infections 7, 1, 2

• Ceftriaxone has superior efficacy for pharyngeal infections and is strongly preferred over oral alternatives 1, 2

• Spectinomycin has only 52% efficacy for pharyngeal infections and should never be used if pharyngeal exposure is suspected 1, 2

Critical Pitfalls to Avoid

• Never use quinolones (ciprofloxacin, ofloxacin) for gonorrhea treatment due to widespread resistance, despite their historical 99% cure rates 1, 8, 2

• Never use azithromycin 1 g alone for gonorrhea treatment - it has insufficient efficacy at only 93% cure rate 1, 2

• Never use ceftriaxone alone without chlamydia coverage unless chlamydial infection has been definitively ruled out 7, 1, 2

Special Populations

• In pregnancy: Use ceftriaxone 500 mg IM (single dose) PLUS azithromycin 1 g orally (single dose) 1, 2
  • Never use doxycycline, quinolones, or tetracyclines in pregnancy 1, 9
  • Amoxicillin 500 mg three times daily for 7 days is an alternative for chlamydia coverage in pregnancy, but this is NOT single-dose 1

Follow-Up Requirements

• Patients treated with the recommended ceftriaxone plus azithromycin regimen do NOT need routine test-of-cure unless symptoms persist 7, 1, 2

• All patients should be retested approximately 3 months after treatment due to high reinfection risk 7, 1

• Mandatory test-of-cure at 1 week is required for patients receiving cefixime-based regimens or azithromycin monotherapy 1, 2

Partner Management

• All sexual partners from the preceding 60 days should be evaluated and treated with the same dual therapy regimen 1, 2

• Patients should avoid sexual intercourse until therapy is completed and both patient and partners are asymptomatic 1, 2