What are the first-line and second-line treatments for gonorrhea?

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Last updated: June 5, 2025View editorial policy

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From the Guidelines

The first-line treatment for gonorrhea is dual therapy with ceftriaxone 500 mg as a single intramuscular injection plus azithromycin 1 gram orally as a single dose, as recommended by the most recent guidelines due to increasing antibiotic resistance in Neisseria gonorrhoeae 1. This combination approach is crucial because ceftriaxone targets the bacterial cell wall while azithromycin inhibits protein synthesis, providing complementary mechanisms of action. For patients with cephalosporin allergies, second-line treatment options include gentamicin 240 mg intramuscular injection plus azithromycin 2 grams orally as a single dose, or gemifloxacin 320 mg orally plus azithromycin 2 grams orally as a single dose. Some key points to consider in the treatment of gonorrhea include:

  • Testing for and treating chlamydia concurrently as co-infection is common 1
  • Treating partners simultaneously to prevent reinfection
  • Patients should abstain from sexual activity until both they and their partners have completed treatment and are symptom-free
  • A test of cure is recommended in certain cases, particularly with alternative regimens or persistent symptoms, typically 1-2 weeks after treatment completion 1 It's also important to note that the emergence of resistance to extended-spectrum cephalosporin antibiotics complicates the treatment of gonorrhea, and pharyngeal infections are particularly challenging due to unfavorable pharmacokinetics of cephalosporins in pharyngeal tissues 1.

From the FDA Drug Label

For the treatment of uncomplicated gonococcal infections, a single intramuscular dose of 250 mg is recommended.

  • First-line treatment: The recommended first-line treatment for gonorrhea is a single intramuscular dose of 250 mg ceftriaxone 2.
  • Second-line treatment: The FDA drug label does not provide information on a second-line treatment for gonorrhea. However, azithromycin is mentioned as a treatment for urethritis and cervicitis due to Neisseria gonorrhoeae, but the dosage and administration for gonorrhea are not specified 3.

From the Research

First-Line Treatment for Gonorrhea

  • The first-line treatment for gonorrhea is dual therapy with ceftriaxone and azithromycin, as recommended by the American College of Obstetricians and Gynecologists (ACOG) 4 and the Centers for Disease Control and Prevention (CDC) 5.
  • This combination therapy is effective against uncomplicated urogenital, anorectal, and pharyngeal gonorrhea, and is also recommended for pregnant women who are infected with N. gonorrhoeae 4.
  • The CDC recommends a single 500 mg intramuscular (IM) dose of ceftriaxone for treatment of uncomplicated urogenital, anorectal, and pharyngeal gonorrhea, and concurrent treatment with doxycycline (100 mg orally twice a day for 7 days) if chlamydial infection has not been excluded 5.

Second-Line Treatment for Gonorrhea

  • Alternative treatment options for gonorrhea include gentamicin plus azithromycin, which has been shown to be effective in treating extragenital gonorrhea 6.
  • A systematic review and network meta-analysis found that azithromycin and ceftriaxone were the most effective antibiotics for the treatment of gonorrhea, and identified gentamicin and ofloxacin as alternative therapeutics to treat drug-resistant gonorrhea 7.
  • In vitro studies have also evaluated the efficacy of various dual antimicrobial combinations, including gentamicin plus ertapenem, moxifloxacin plus ertapenem, and spectinomycin plus ertapenem, which may be considered as alternative treatment options in the future 8.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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