Gonorrhea: Site-Specific Antimicrobial Treatment

Testing by exposure site

Use nucleic acid amplification testing (NAAT) at the urogenital, rectal, and/or pharyngeal sites identified by exposure. Urine alone misses extragenital infection. Ask about pelvic pain, testicular symptoms, ocular involvement, disseminated rash or arthritis, and pregnancy. Consider culture with susceptibility testing when treatment failure is suspected because molecular tests do not supply conventional antimicrobial susceptibility results. Offer testing for chlamydia, syphilis, HIV, and other infections as clinically appropriate (Smith & Honeywell, 2026).

Recommended uncomplicated treatment

Ceftriaxone 500 mg IM once is the standard regimen for uncomplicated cervical, urethral, rectal, or pharyngeal gonorrhea in patients weighing less than 150 kg; patients weighing 150 kg or more receive 1 g IM once. If concurrent chlamydia has not been excluded in a nonpregnant patient, add doxycycline 100 mg orally twice daily for seven days. In pregnancy, use a pregnancy-appropriate chlamydia regimen when needed. For a serious beta-lactam allergy, evaluate the exact reaction, site, and alternative regimen with specialist or public-health guidance, particularly for pharyngeal infection (Smith & Honeywell, 2026).

Follow-up and public health management

For pharyngeal gonorrhea, arrange a test of cure 7–14 days after treatment; nucleic acid testing too early can yield misleading positives. Retest approximately three months after treatment because reinfection is common. Evaluate and treat sexual partners from the preceding 60 days, subject to exposure and local expedited-partner-therapy rules. Advise abstinence for seven days after treatment and until partners are treated and symptoms have resolved. Report infections according to applicable public-health requirements (Smith & Honeywell, 2026).

Treatment failure and resistance

Persistent symptoms after appropriately administered therapy require review of re-exposure, correct anatomic sampling, susceptibility testing, and communication with an infectious disease or public-health consultant. Do not use ciprofloxacin empirically without documented susceptibility. Newer oral agents may be available for narrowly defined indications or limited alternatives; they should not replace ceftriaxone reflexively, particularly for pharyngeal disease (Smith & Honeywell, 2026).

FDA-approved oral gonorrhea agents: indication-specific alternatives

FDA-approved oral therapy for uncomplicated urogenital gonorrhea now includes two distinct options. Gepotidacin (Blujepa) is labeled only for eligible patients at least 12 years old and at least 45 kg with limited or no alternative treatment options: 3,000 mg orally after a meal, then 3,000 mg approximately 12 hours later. Important exclusions include QTc risk, relevant QT-prolonging drugs, severe renal/hepatic impairment, and interacting CYP3A4 medications. Zoliflodacin (Nuzolvence) is labeled for eligible patients at least 12 years old and at least 35 kg at 3 g orally once. Its granules must be mixed with water and administered within 15 minutes; patients 35 to under 50 kg take it fasting, whereas those at least 50 kg take it with food. Pregnancy testing and reproductive-toxicity counseling, including precautions for male partners, are needed. Neither label establishes treatment of pharyngeal gonorrhea, disseminated disease or PID. FDA approval does not establish CDC first-line status. Ceftriaxone remains the CDC-recommended treatment for routine uncomplicated gonorrhea, including pharyngeal infection; the oral labels do not establish treatment for pharyngeal infection (U.S. Food and Drug Administration, 2025a, 2025b; CDC, 2021, Gonococcal Infections).

Site-by-site decision summary

For urogenital and rectal infection, choose guideline-directed ceftriaxone with chlamydia coverage when infection is not excluded and arrange three-month reinfection screening. For pharyngeal gonorrhea, confirm the drug choice is effective at that site and arrange a test of cure at 7–14 days. Suspected dissemination, pregnancy with major medication allergy, treatment failure, or complicated ocular infection merits specialist/public-health coordination. A positive urine NAAT cannot substitute for testing exposed throat or rectal sites (Smith & Honeywell, 2026).

Anatomy and allergy determine the fallback path

For uncomplicated urogenital, rectal, or pharyngeal infection, ceftriaxone remains the default first-line agent with weight-based dosing. Pharyngeal infection is particularly important because available alternatives are less well established and test of cure is recommended. If ceftriaxone cannot be used, clarify whether the reaction represents a true severe cephalosporin allergy, and involve STI expertise before selecting an alternative. Treat chlamydia when it has not been excluded, but do not automatically pair treatment when a negative NAAT reliably excludes it (Smith & Honeywell, 2026).

New oral agents have narrower evidence boundaries

Before prescribing an oral alternative for gonorrhea, verify the anatomic infection site, patient age and weight, pregnancy status, indication restrictions, drug interactions, and availability of an effective conventional regimen. Blujepa is limited to uncomplicated urogenital infection in eligible patients with limited or no alternatives and requires careful assessment of QTc risk, renal/hepatic status, and CYP3A4 interactions. Nuzolvence is also restricted to uncomplicated urogenital infection and requires a pregnancy test, review of CYP3A4 inducer use, administration instructions, and reproductive-risk counseling. Its labeling advises males with female partners of reproductive potential to use effective contraception for at least three months after administration. Neither agent has an established labeled indication for pharyngeal, rectal, disseminated infection, or PID; do not substitute one merely for convenience. Product-specific regimen and meal instructions must also be followed (U.S. Food and Drug Administration, 2025a, 2025b).

Clinical application

A patient weighing 162 kg has urogenital gonorrhea and a negative chlamydia NAAT but reports recent oral exposure. Obtain the appropriate pharyngeal specimen; use the guideline weight threshold for ceftriaxone rather than a routine 500-mg dose in a patient at least 150 kg. If pharyngeal infection is confirmed, arrange test of cure and partner care. Do not choose a newly approved oral urogenital-only option merely to avoid an injection; reserve alternative planning for genuine contraindications and verified indications (Smith & Honeywell, 2026).

High-yield distinctions

A 150-kg weight threshold changes ceftriaxone dosing. Chlamydia treatment is additional when coinfection is not excluded. Pharyngeal gonorrhea requires test-of-cure follow-up.

Related YourDNP Resources

Pharmacology learning hub · Chlamydia and genital warts · Pelvic inflammatory disease · Syphilis

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References

Centers for Disease Control and Prevention. (2021). Gonococcal infections. STI treatment guidelines. https://www.cdc.gov/std/treatment-guidelines/gonorrhea-adults.htm

Smith, U. D., & Honeywell, M. S. (2026). Sexually transmitted infections. In M. A. Chisholm-Burns, P. M. Malone, J. M. Kolesar, K. C. Lee, P. B. Bookstaver, & K. R. Matthias (Eds.), Pharmacotherapy principles & practice (7th ed., Chapter 83). McGraw Hill.

U.S. Food and Drug Administration. (2025a). Blujepa (gepotidacin) tablets: Prescribing information (NDA 218230/S-001). https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/218230s001lbl.pdf

U.S. Food and Drug Administration. (2025b). Nuzolvence (zoliflodacin): Prescribing information (NDA 219491). https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/219491Orig1s000lbl.pdf