What is the recommended treatment regimen for gonorrhea?

Gonorrhea Treatment

Primary Recommendation

Treat uncomplicated gonorrhea with ceftriaxone 500 mg intramuscularly as a single dose, plus azithromycin 1 g orally as a single dose for presumptive chlamydia coverage. 1, 2

This dual therapy regimen represents the current standard of care based on CDC's 2020 updated guidelines, which increased the ceftriaxone dose from 250 mg to 500 mg to maintain efficacy against evolving resistance patterns. 2

Rationale for Current Regimen

Why Ceftriaxone 500 mg?

• Ceftriaxone achieves 99.1% cure rates for uncomplicated urogenital and anorectal gonorrhea, making it the most effective injectable antibiotic available (p score 0.924 in network meta-analysis). 1, 3

• The 500 mg dose is specifically required for pharyngeal infections, which are significantly more difficult to eradicate than urogenital or anorectal sites—most ceftriaxone treatment failures occur in the pharynx. 1

• Ceftriaxone is the only reliably effective treatment for pharyngeal gonorrhea, with superior efficacy compared to all oral alternatives. 1

Why Add Azithromycin?

• Co-infection with chlamydia occurs in 40-50% of gonorrhea cases, making presumptive dual treatment essential when empiric therapy is indicated. 1

• Azithromycin 1 g provides single-dose chlamydia coverage, eliminating compliance issues associated with 7-day doxycycline regimens. 1

• Azithromycin is preferred over doxycycline due to convenience and substantially higher prevalence of gonococcal resistance to tetracyclines. 1

• However, azithromycin 1 g alone is insufficient for gonorrhea treatment (only 93% efficacy) and should never be used as monotherapy. 1, 4

Alternative Regimens

When Ceftriaxone is Unavailable

Use cefixime 400 mg orally once PLUS azithromycin 1 g orally once, with mandatory test-of-cure at 1 week. 1, 5, 6

• Critical caveat: Cefixime is less effective than ceftriaxone, particularly for pharyngeal infections, due to rising MICs and declining effectiveness. 1, 5

• Test-of-cure is mandatory at 1 week when using this regimen due to inferior efficacy. 1

For Severe Cephalosporin Allergy

Use azithromycin 2 g orally once, with mandatory test-of-cure at 1 week. 1, 5

• This regimen has lower efficacy (only 93%) and high gastrointestinal side effects (35.3% of patients experience GI symptoms, with 2.9% severe). 1, 4

• Alternative option: Gentamicin 240 mg IM once PLUS azithromycin 2 g orally once achieved 100% cure rates in clinical trials. 1, 3

• Avoid spectinomycin for pharyngeal infections—it has only 52% efficacy at this site. 1

Special Populations

Pregnant Women

Use ceftriaxone 500 mg IM once PLUS azithromycin 1 g orally once. 1, 5

• Never use quinolones or tetracyclines in pregnancy—both are contraindicated. 1, 5, 7

• Ceftriaxone is the preferred cephalosporin in pregnancy. 1, 5

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, 5

• Do not use quinolones in MSM—resistance rates are too high. 1, 5

• Do not use patient-delivered partner therapy in MSM due to high risk of undiagnosed coexisting STDs or HIV. 1

Neonates

Ceftriaxone is contraindicated in premature neonates and in neonates ≤28 days requiring calcium-containing IV solutions due to risk of fatal ceftriaxone-calcium precipitation. 7

• For neonates who can receive ceftriaxone, administer IV doses over 60 minutes to reduce risk of bilirubin encephalopathy. 7

• Do not treat hyperbilirubinemic neonates with ceftriaxone. 7

Critical Pitfalls to Avoid

Never Use These Regimens

• Never use fluoroquinolones (ciprofloxacin, ofloxacin) for gonorrhea treatment due to widespread resistance, despite historical 99.8% cure rates. 1, 8

• Never use azithromycin 1 g alone for gonorrhea—93% efficacy is insufficient. 1

• Never use spectinomycin or gentamicin for pharyngeal infections—both have poor pharyngeal efficacy (52% and 20% respectively). 1

Site-Specific Considerations

• Pharyngeal gonorrhea requires ceftriaxone—it is more difficult to eradicate than urogenital or anorectal infections, and ceftriaxone has superior efficacy for this site. 1, 5

• Ceftriaxone 500 mg is strongly preferred over cefixime for pharyngeal infections. 1

Partner Management

Evaluate and treat all sex partners from the preceding 60 days. 1, 5

• If the patient's last sexual contact was >60 days before diagnosis, treat the most recent partner. 5

• Partners should receive the same dual therapy regimen (ceftriaxone plus azithromycin). 1

• Consider expedited partner therapy with oral combination therapy (cefixime 400 mg plus azithromycin 1 g) if partners cannot be linked to timely evaluation. 1, 5

• Patients should avoid sexual intercourse until therapy is completed and both they and their partners are asymptomatic. 1

Follow-Up Requirements

Routine Follow-Up

Patients treated with recommended regimens (ceftriaxone plus azithromycin) do not need routine test-of-cure unless symptoms persist. 1

• Consider retesting all patients 3 months after treatment due to high reinfection rates (9.9% retreated within 2 years). 1, 9

Mandatory Test-of-Cure Situations

Test-of-cure at 1 week is mandatory for:

• Patients receiving cefixime plus azithromycin 1
• Patients receiving azithromycin 2 g monotherapy 1, 5
• Patients with persistent symptoms 1

If Symptoms Persist

Obtain culture with antimicrobial susceptibility testing immediately. 1

• If NAAT is positive at follow-up, confirm with culture and perform phenotypic antimicrobial susceptibility testing on all positive cultures. 1

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 PLUS azithromycin 2 g orally (single dose) 1
• Ertapenem 1 g IM for 3 days 1
• Spectinomycin 2 g IM PLUS azithromycin 2 g orally (avoid for pharyngeal infections) 1

Concurrent Testing

Screen for syphilis with serology at the time of gonorrhea diagnosis. 5

• Test for other sexually transmitted infections, including HIV, as gonorrhea should prompt comprehensive STI screening. 8