What is the best antibiotic treatment for gonorrhea?

Best Antibiotic for Gonorrhea

The best antibiotic treatment for gonorrhea is ceftriaxone 500 mg intramuscularly as a single dose, which should be combined with doxycycline 100 mg orally twice daily for 7 days if chlamydial coinfection has not been excluded. 1

Primary Treatment Regimen

Ceftriaxone 500 mg IM once is now the recommended first-line monotherapy for uncomplicated gonorrhea at all anatomic sites (urogenital, rectal, and pharyngeal). 1 This represents an increase from the previous 250 mg dose based on updated pharmacokinetic/pharmacodynamic data and antimicrobial stewardship principles. 1

Key Changes from Previous Guidelines

• Azithromycin is no longer routinely recommended as part of dual therapy due to rapidly rising resistance, with nearly 5% of U.S. isolates showing elevated azithromycin MICs (≥2.0 mcg/mL) by 2018. 1
• The older dual therapy regimen (ceftriaxone 250 mg + azithromycin 1 g) was recommended in 2012-2015 guidelines 2, but resistance patterns have evolved significantly since then.
• Add doxycycline 100 mg orally twice daily for 7 days only if chlamydial coinfection has not been excluded, as coinfection occurs in 40-50% of gonorrhea cases. 3

Rationale for Current Recommendations

Ceftriaxone remains highly effective with stable resistance patterns in the United States, with <0.1% of isolates showing elevated MICs (>0.25 mcg/mL). 1 The higher 500 mg dose provides:

• Superior bactericidal levels at all anatomic sites 1
• Enhanced efficacy against pharyngeal infections, which are notoriously difficult to eradicate 3
• A buffer against emerging resistance 1

Azithromycin monotherapy (even 2 g) is insufficient, with only 93% efficacy for gonorrhea treatment. 3 The rapid rise in azithromycin resistance makes it unsuitable as a routine component of dual therapy. 1

Alternative Regimens (When Ceftriaxone Unavailable)

If ceftriaxone is not available:

• Cefixime 400 mg orally once PLUS azithromycin 1 g orally once 2, 3, 4
• Mandatory test-of-cure at 1 week is required with this regimen 2, 3
• Cefixime has significantly lower efficacy for pharyngeal gonorrhea (limited effectiveness) and provides less sustained bactericidal levels than ceftriaxone 2, 4

Severe Cephalosporin Allergy

For patients with severe cephalosporin allergy:

• Gentamicin 240 mg IM once PLUS azithromycin 2 g orally once demonstrates 100% cure rates in clinical trials 3, 5
• Alternative: Azithromycin 2 g orally once alone (lower efficacy at 93%, high GI side effects) 2, 3
• Mandatory test-of-cure at 1 week 2, 3

Critical caveat: Gentamicin has poor pharyngeal efficacy (only 20% cure rate), so avoid for pharyngeal infections. 3

Special Populations

Men Who Have Sex with Men (MSM)

• Use only ceftriaxone 500 mg IM due to higher prevalence of resistant strains in this population 3, 4
• Never use quinolones (ciprofloxacin, ofloxacin) in MSM due to widespread resistance 3

Pregnant Women

• Ceftriaxone 500 mg IM once PLUS azithromycin 1 g orally once is the preferred regimen 3, 6, 7
• Never use quinolones or tetracyclines in pregnancy 3, 4
• If injection is refused, cefixime 400 mg orally PLUS azithromycin 1 g orally can be considered, though less effective 4

Site-Specific Considerations

Pharyngeal gonorrhea requires special attention as it is significantly more difficult to eradicate than urogenital or anorectal infections. 3

• Ceftriaxone 500 mg IM is the only reliably effective treatment for pharyngeal infections 3
• Oral cephalosporins (cefixime) have limited efficacy for pharyngeal disease 2
• Spectinomycin has only 52% efficacy for pharyngeal infections 3

Critical Pitfalls to Avoid

• Never use fluoroquinolones (ciprofloxacin, ofloxacin) for gonorrhea treatment due to widespread resistance, despite historical 99.8% cure rates 3
• Never use azithromycin 1 g alone for gonorrhea treatment (only 93% efficacy) 3, 8
• Never substitute oral cephalosporins as first-line therapy due to documented treatment failures in Europe 4
• Do not use spectinomycin or gentamicin for pharyngeal infections due to poor efficacy 3

Follow-Up and Partner Management

Test-of-Cure Requirements

• Not needed for patients treated with recommended ceftriaxone regimen 6, 7
• Mandatory at 1 week for patients receiving cefixime or azithromycin monotherapy 2, 3
• If symptoms persist after treatment, obtain culture with antimicrobial susceptibility testing 3, 4

Partner Management

• Evaluate and treat all sexual partners from the preceding 60 days 3, 4
• Partners should receive the same dual therapy regimen 3
• Retest all patients 3 months after treatment due to high reinfection rates (40-50%) 6, 7

Concurrent Testing

• Screen for syphilis with serology at time of gonorrhea diagnosis 3, 4
• Test for HIV given gonorrhea's facilitation of HIV transmission 3
• Test for chlamydia to guide need for doxycycline 1

Treatment Failure Management

If treatment failure occurs:

• Obtain specimens for culture and antimicrobial susceptibility testing immediately 3
• Report to local public health officials within 24 hours 3
• Consult an infectious disease specialist 3
• Salvage regimens include gentamicin 240 mg IM PLUS azithromycin 2 g orally, or ertapenem 1 g IM for 3 days 3