Is doxycycline (DOX) 100mg twice daily (bid), ceftriaxone (CRO) 1g every 24 hours (q24h), and azithromycin (AZM) 1g orally (po) once effective for treating gonorrhea?

Gonorrhea Treatment: The Proposed Regimen is Excessive and Suboptimal

The combination of doxycycline 100mg BID, ceftriaxone 1g q24h, and azithromycin 1g PO x1 is NOT the recommended treatment for gonorrhea—you should use ceftriaxone 500mg IM as a single dose (not 1g daily) plus azithromycin 1g PO as a single dose (preferred) OR doxycycline 100mg BID for 7 days, not all three agents together. 1, 2

Critical Problems with the Proposed Regimen

Ceftriaxone Dosing is Wrong

• CDC guidelines recommend ceftriaxone 250-500mg IM as a SINGLE dose, not 1g daily. 1, 3
• The 2020 update increased the dose to 500mg IM single dose for uncomplicated urogenital, anorectal, and pharyngeal gonorrhea. 3
• There is no indication for daily dosing of ceftriaxone in uncomplicated gonorrhea—this represents unnecessary antimicrobial exposure and cost. 1, 2

Redundant Second Agent

• You should use EITHER azithromycin OR doxycycline as the second agent, not both simultaneously. 1, 2
• Azithromycin 1g PO single dose is strongly preferred over doxycycline due to:
  • Single-dose convenience improving compliance 1, 2
  • Substantially lower tetracycline resistance rates (0.6% vs 77.2% in strains with elevated cefixime MICs) 2
  • High prevalence of tetracycline resistance among Gonococcal Isolate Surveillance Project isolates 1, 2

Correct Treatment Algorithm

First-Line Recommended Regimen

• Ceftriaxone 500mg IM single dose PLUS azithromycin 1g PO single dose 3, 2
• This treats both gonorrhea and presumptive chlamydial co-infection 1

Alternative Second Agent (When Azithromycin Not Preferred)

• Ceftriaxone 500mg IM single dose PLUS doxycycline 100mg PO BID for 7 days 1, 2
• Use this only when azithromycin is contraindicated or unavailable 1, 2

If Ceftriaxone Unavailable

• Cefixime 400mg PO single dose PLUS azithromycin 1g PO (or doxycycline 100mg BID x 7 days) PLUS mandatory test-of-cure in 1 week 1, 2

Severe Cephalosporin Allergy

• Azithromycin 2g PO single dose PLUS test-of-cure in 1 week 1, 4, 2
• Consult infectious disease specialist 4

Evidence Supporting Single-Dose Ceftriaxone

Efficacy Data

• Recent high-quality RCT showed ceftriaxone 1g IV plus doxycycline achieved 96.7% cure rate for NG-CT co-infection 5
• However, standard 250-500mg IM dosing remains guideline-recommended as adequate for uncomplicated cases 1, 3
• A 2024 RCT demonstrated ceftriaxone 1g IM plus azithromycin 2g achieved 100% cure rate across all sites 6

Why Not Daily Dosing?

• Gonorrhea is treated with single-dose therapy because ceftriaxone achieves sustained therapeutic levels at infected sites 1
• Daily dosing provides no additional benefit and increases antimicrobial stewardship concerns 3
• The 2020 CDC update specifically moved away from dual therapy to reduce unnecessary antimicrobial exposure 3

Critical Caveats

Test-of-Cure Requirements

• Mandatory for pharyngeal gonorrhea treated with alternative regimens 1, 2
• Perform at 1 week using culture (preferred) or NAAT 1, 4
• Pharyngeal gonorrhea has higher treatment failure rates—cefixime plus doxycycline showed only 86% efficacy when pharyngeal cases included 6

Partner Management

• All sex partners from preceding 60 days must be evaluated and treated 1
• Expedited partner therapy reduces retreatment rates by 45% 7
• Use cefixime 400mg plus azithromycin 1g for expedited partner therapy 1

Chlamydia Co-Treatment

• If chlamydial infection not excluded, concurrent treatment is essential 3
• Doxycycline 100mg BID for 7 days is recommended when chlamydia testing unavailable 3
• High rates of co-infection (up to 40%) justify presumptive treatment 1

Common Pitfalls to Avoid

• Do not use doxycycline as monotherapy for gonorrhea—tetracycline resistance is too high 1, 2
• Do not use both azithromycin AND doxycycline together—choose one based on resistance patterns and compliance 1, 2
• Do not continue ceftriaxone beyond single dose for uncomplicated cases—this is antimicrobial overuse 3
• Do not forget test-of-cure for alternative regimens or treatment failures—culture with susceptibility testing is critical 1, 4