Treatment of Gonorrhoea
Primary Recommendation
For uncomplicated gonorrhoea of the cervix, urethra, rectum, and pharynx, administer ceftriaxone 500 mg intramuscularly as a single dose PLUS azithromycin 1 g orally as a single dose. 1, 2
This dual therapy achieves a 99.1% cure rate for urogenital and anorectal infections and is the only reliably effective regimen for pharyngeal gonorrhoea. 1, 3
Rationale for Dual Therapy
Dual therapy addresses two critical issues: (1) presumptive treatment of chlamydial co-infection, which occurs in 40-50% of gonorrhoea cases, and (2) potential delay in emergence of cephalosporin resistance through combination therapy. 1, 4
If chlamydial infection has been definitively excluded by testing, doxycycline 100 mg orally twice daily for 7 days may be substituted for azithromycin to reduce selective pressure on commensal organisms, though azithromycin offers superior compliance with single-dose administration. 1, 2
Ceftriaxone Dosing Considerations
Standard Dosing (All Body Weights)
Ceftriaxone dosing is NOT weight-based in adults—the standard 500 mg intramuscular dose is used regardless of body habitus, including patients weighing >150 kg. 3
Clinical trials using 250-500 mg ceftriaxone across varying patient weights consistently achieved 98.9-99.1% cure rates, confirming dose adequacy without adjustment. 3
Historical Context
- The CDC previously recommended 250 mg ceftriaxone but increased the dose to 500 mg in 2020 to maintain a therapeutic reserve against emerging resistance, despite no documented ceftriaxone-resistant strains in the United States. 3, 2
Alternative Regimens
When Ceftriaxone Is Unavailable
Administer cefixime 400 mg orally as a single dose PLUS azithromycin 1 g orally as a single dose, with mandatory test-of-cure at 1 week. 1, 4
Cefixime achieves only 97.4% overall cure and 78.9% cure for pharyngeal infections, significantly lower than ceftriaxone's 99.1% and near-100% pharyngeal efficacy. 1, 4
Test-of-cure should use culture (preferred, allows susceptibility testing) or nucleic acid amplification test (NAAT); if NAAT is positive, confirm with culture and perform antimicrobial susceptibility testing. 1
Severe β-Lactam Allergy
For patients with documented severe cephalosporin allergy, administer azithromycin 2 g orally as a single dose, with mandatory test-of-cure at 1 week. 1
This regimen has only 93% efficacy and high gastrointestinal side effects (nausea, vomiting). 1
Spectinomycin 2 g intramuscularly is an alternative but achieves only 52% cure for pharyngeal infections and should be avoided if pharyngeal exposure is suspected. 5, 1, 4
Gentamicin 240 mg intramuscularly PLUS azithromycin 2 g orally achieved 100% cure in clinical trials for urogenital infections but only 80% for pharyngeal and 90% for rectal infections, making it unsuitable as first-line therapy. 6, 7
Special Populations
Pregnancy
Pregnant women should receive ceftriaxone 500 mg intramuscularly PLUS azithromycin 1 g orally as a single dose. 5, 1, 4
Quinolones, tetracyclines, and doxycycline are absolutely contraindicated in pregnancy due to fetal safety concerns. 5, 1, 4
If severe cephalosporin allergy is documented, spectinomycin 2 g intramuscularly PLUS azithromycin 1 g orally may be used, though pharyngeal efficacy remains poor. 5, 1
Men Who Have Sex with Men (MSM)
Ceftriaxone is the ONLY recommended treatment for MSM due to higher prevalence of resistant strains in this population. 1
Quinolones must never be used in MSM because of documented resistance patterns. 1
Patient-delivered partner therapy should NOT be offered to MSM due to high risk of undiagnosed co-existing sexually transmitted infections or HIV. 1
Patients with Recent Foreign Travel
Ceftriaxone 500 mg intramuscularly is the only recommended treatment due to increased risk of resistant strains acquired internationally. 1
Site-Specific Considerations
Pharyngeal Gonorrhoea
Pharyngeal infections are significantly more difficult to eradicate than urogenital or anorectal infections—ceftriaxone is the ONLY reliably effective treatment. 1, 4
Oral cephalosporins (cefixime) cure only 78.9% of pharyngeal infections. 1, 4
Spectinomycin has only 52% pharyngeal efficacy and should never be used for suspected pharyngeal exposure. 5, 1, 4
Gentamicin achieved only 80% pharyngeal cure in clinical trials, compared to 96% with ceftriaxone. 6, 7
Gonococcal Conjunctivitis
Administer ceftriaxone 1 g intramuscularly as a single dose PLUS lavage the infected eye with saline solution once. 5, 1
Disseminated Gonococcal Infection (DGI)
Hospitalization is recommended for initial therapy. 5, 1
Initial regimen: Ceftriaxone 1 g intramuscularly or intravenously every 24 hours. 5, 1
Continue parenteral therapy for 24-48 hours after clinical improvement, then switch to oral cefixime 400 mg twice daily to complete a total of 1 week of therapy. 1
For β-lactam allergy: Spectinomycin 2 g intramuscularly every 12 hours is an alternative. 5, 1
Assess for endocarditis and meningitis; provide presumptive treatment for concurrent chlamydial infection. 5, 1
Partner Management
All sexual partners from the preceding 60 days must be evaluated and treated with the same dual therapy regimen (ceftriaxone 500 mg IM + azithromycin 1 g orally), regardless of symptoms or test results. 5, 1, 4
If the patient's last sexual contact occurred >60 days before symptom onset or diagnosis, treat the most recent partner. 5
Patients must abstain from sexual intercourse until therapy is completed and both patient and all partners are asymptomatic. 5, 1, 4
Expedited Partner Therapy (EPT)
EPT with oral combination therapy (cefixime 400 mg + azithromycin 1 g) may be considered when partners cannot be linked to timely clinical evaluation. 1
EPT should NOT be offered to MSM due to high risk of undiagnosed co-existing sexually transmitted infections or HIV. 1
Female partners receiving EPT must be counseled to seek clinical evaluation for possible pelvic inflammatory disease. 1
Follow-Up and Test-of-Cure
Routine Follow-Up
Patients treated with the recommended ceftriaxone-based regimen do NOT require routine test-of-cure unless symptoms persist. 1, 4
- Consider retesting all patients at 3 months due to high reinfection risk (most post-treatment positive tests represent reinfection, not treatment failure). 5, 1
Mandatory Test-of-Cure Scenarios
Test-of-cure at 1 week is MANDATORY for:
- Patients treated with cefixime-based regimens 1, 4
- Patients treated with azithromycin 2 g monotherapy 1
- Patients treated with spectinomycin for suspected pharyngeal infection 1
Persistent Symptoms or Treatment Failure
If symptoms persist after treatment:
Obtain specimens from all potentially infected sites for culture with 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:
Contraindicated Medications
Fluoroquinolones
Fluoroquinolones (ciprofloxacin, ofloxacin, levofloxacin) are ABSOLUTELY CONTRAINDICATED for gonorrhoea treatment due to widespread resistance, despite historical cure rates of 99.8%. 5, 1, 4
Azithromycin Monotherapy
Azithromycin 1 g alone should NEVER be used for gonorrhoea treatment—it achieves only 93% efficacy and risks rapid resistance emergence. 1, 4
Ancillary Screening
Screen for syphilis with serology at the time of gonorrhoea diagnosis, given high rates of co-infection and overlapping risk factors. 1, 4
Perform HIV co-testing, as gonorrhoea facilitates HIV transmission. 1
Common Pitfalls to Avoid
Never use oral cephalosporins other than cefixime (e.g., cefuroxime, cefpodoxime)—they are ineffective for pharyngeal infections. 4
Never assume symptom resolution equals cure when suboptimal regimens were used—test-of-cure is mandatory in these scenarios. 1
Never omit chlamydia treatment when empiric gonorrhoea therapy is indicated, even if chlamydia testing is negative, due to 40-50% co-infection rates. 1, 4
Never use spectinomycin or gentamicin for pharyngeal infections—both have poor pharyngeal efficacy (52% and 80%, respectively). 1, 6, 7