What is the recommended treatment regimen for gonorrhoea?

Gonorrhea Treatment

The recommended first-line treatment for uncomplicated gonorrhea is ceftriaxone 500 mg intramuscularly as a single dose PLUS azithromycin 1 g orally as a single dose. 1, 2, 3

Primary Treatment Regimen

• Ceftriaxone 500 mg IM (single dose) + azithromycin 1 g orally (single dose) is the CDC-recommended dual therapy for all uncomplicated gonococcal infections of the cervix, urethra, rectum, and pharynx 1, 2, 3

• This regimen achieves a 99.1% cure rate for urogenital and anorectal gonorrhea 1

• Dual therapy is essential because 40-50% of gonorrhea patients have concurrent chlamydial infection, and combination therapy helps prevent emergence of cephalosporin resistance 1, 2

• Both medications should be administered together on the same day, preferably simultaneously and under direct observation 4

Rationale for Current Dosing

• The CDC increased the ceftriaxone dose from 250 mg to 500 mg in 2020 to maintain efficacy against strains with reduced cephalosporin susceptibility 3

• Azithromycin is preferred over doxycycline for chlamydia coverage due to single-dose convenience and substantially higher compliance, though doxycycline 100 mg orally twice daily for 7 days is acceptable if chlamydial infection has been excluded 1, 3

Alternative Regimens (When Ceftriaxone Unavailable)

• Cefixime 400 mg orally (single dose) + azithromycin 1 g orally (single dose) can be used if ceftriaxone is unavailable 1, 5
  • Mandatory test-of-cure at 1 week is required with this regimen due to inferior efficacy compared to ceftriaxone 1, 2
  • Cefixime has only 97.1% cure rate for urogenital/anorectal infections 6

Severe Cephalosporin Allergy

• Azithromycin 2 g orally (single dose) is the option for patients with severe cephalosporin allergy 1

  • Requires mandatory test-of-cure at 1 week 1
  • Has lower efficacy (93% cure rate) and causes significant gastrointestinal side effects in 35.3% of patients 1, 7

• Gentamicin 240 mg IM + azithromycin 2 g orally is an alternative non-cephalosporin regimen with 100% cure rate in clinical trials 1, 8

  • However, gentamicin has poor pharyngeal efficacy (only 20% cure rate) and should be avoided if pharyngeal exposure is suspected 1

Site-Specific Considerations: Pharyngeal Gonorrhea

• Pharyngeal gonorrhea is substantially more difficult to eradicate than urogenital or anorectal infections 1, 9

• Ceftriaxone is the only reliably effective treatment for pharyngeal infections, with cure rates exceeding 90% 9

• Cefixime has inferior efficacy for pharyngeal infections and should not be used 9

• Spectinomycin has only 52% efficacy for pharyngeal infections and must be avoided 1, 2

Critical Pitfalls to Avoid

• Never use fluoroquinolones (ciprofloxacin, ofloxacin) for gonorrhea treatment due to widespread resistance, despite their historical 99.8% cure rates 1, 2, 9

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

• Never use oral cephalosporins as first-line agents due to documented treatment failures in Europe 1

Special Populations

Pregnancy

• Use the same recommended regimen: ceftriaxone 500 mg IM + azithromycin 1 g orally 1, 2, 4
• Never use quinolones, tetracyclines, or doxycycline in pregnancy 1, 9
• Pregnant women with antenatal gonococcal infection should be retested in the third trimester 4

Men Who Have Sex with Men (MSM)

• Ceftriaxone is the only recommended treatment due to higher prevalence of resistant strains in this population 1
• Never use quinolones for MSM 1
• Do not use patient-delivered partner therapy due to high risk of undiagnosed coexisting STDs or HIV 1

Neonates

• Intravenous doses should be given over 60 minutes to reduce risk of bilirubin encephalopathy 10
• Do not use diluents containing calcium 10

Follow-Up Requirements

• Routine test-of-cure is NOT needed for patients treated with the recommended ceftriaxone plus azithromycin regimen unless symptoms persist 1, 2, 9

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

• Retest all patients at 3 months after treatment due to high reinfection risk (not treatment failure) 1, 2

• If symptoms persist after treatment, obtain culture with antimicrobial susceptibility testing and consult an infectious disease specialist 1, 9

Treatment Failure Management

• If treatment failure occurs, obtain specimens for culture and antimicrobial susceptibility testing immediately 1

• Report the case to local public health officials within 24 hours 1

• Consult an infectious disease specialist 1

• Recommended salvage regimens include:

  • Gentamicin 240 mg IM + azithromycin 2 g orally (single dose) 1
  • Ertapenem 1 g IM for 3 days 1

Partner Management

• All sexual partners from the preceding 60 days must be evaluated and treated with the same dual therapy regimen 1, 2, 9

• Partners should receive treatment for both gonorrhea and chlamydia regardless of symptoms 1

• Patients must avoid all sexual intercourse until therapy is completed and both patient and all partners are asymptomatic 1, 2, 9

• Expedited partner therapy with oral combination therapy (cefixime 400 mg + azithromycin 1 g) may be considered if partners cannot be linked to timely evaluation 1

Additional Screening

• Screen for syphilis with serology at the time of gonorrhea diagnosis 1

• Co-test for HIV given that gonorrhea facilitates HIV transmission 1