Urethritis Treatment & Management

Updated: Oct 03, 2022
  • Author: Dustin L Whitaker, MD; Chief Editor: Edward David Kim, MD, FACS  more...
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Medical Care

Symptoms of urethritis typically resolve spontaneously over time, regardless of treatment. Administer antibiotics to prevent morbidity and to reduce disease transmission to others. Treating recent sexual contacts (those having sexual contact with the patient within 60 days prior to symptom onset) also prevents reinfection of the index patient.

Dual antibiotic therapy is the mainstay treatment for urethritis. Antibiotic therapy should cover both gonococcal urethritis (GU) and nongonococcal urethritis (NGU). If concomitant treatment for NGU is not provided, the risk of postgonococcal urethritis is approximately 50%. Dual therapy also has a theoretical benefit of slowing the emergence and rapid spread of antimicrobial resistance. The choice of antibiotics should be based on cost, adverse effects, effectiveness, and compliance. In most situations, optimal treatment is with single-dose therapy administered in the emergency department or the physician's office.

The treatment of Neisseria gonorrhoeae has become increasingly complex due to the evolution of antimicrobial resistance and the decreased use of culture given widespread utilization of nucleic acid amplification tests (NAATs). In 2014, the Gonococcal Isolate Surveillance Project (GISP) reported that 25% of N gonorrhoeae isolates were resistant to tetracycline, 19.2% were resistant to ciprofloxacin, and 16.2% were resistant to penicillin. Reduced susceptibility to azithromycin was also noted. [14]   Currently, the Centers for Disease Control and Prevention (CDC) recommends a single dose of ceftriaxone 250 mg IM and azithromycin 1 g orally for the treatment of GU; preferably, the two antibiotics should be administered simultaneously and under direct observation. If ceftriaxone is unavailable, administer cefixime 400 mg orally in a single dose. If the patient has a cephalosporin allergy or a type 1 hypersensitivity reaction to penicillins, treat with azithromycin, 2 g orally, plus either gemifloxacin 320 mg orally or gentamicin 240 mg IM. [26]  

Gonorrhea treatment guidelines issued by the World Health Organization (WHO) in 2016 recommend determining the choice of therapy on the basis of local antibiotic resistance data, but in settings where local resistance data are not available, the WHO recommends the same dual-therapy regimens as the CDC for treatment of genital gonorrhea. [27]

Because of widespread high levels of resistance, the WHO guidelines do not recommend fluoroquinolones for the treatment of gonorrhea. For monotherapy of genital gonorrhea, the WHO guidelines recommend a single dose of one of the following, with the choice based on recent local resistance data confirming susceptibility [27] : ceftriaxone 250 mg IM, cefixime 400 mg orally, or spectinomycin 2 g IM.

For treatment of NGU, the CDC currently recommends doxycycline, 100 mg orally twice a day for 7 days.  Alternative regimens include A single dose of orally of 1g azithromycin or 500 mg orally followed by 250 mg orally daily for 4 days. [4]   The American Academy of Family Physicians recommends a single dose of ceftriaxone, 500mg IM, plus doxycycline, 100 mg orally twice a day for seven days. [22]

The CDC no longer recommends erythromycin or levofloxacin for treatment of NGU. [4]

Patients with persistent symptoms should be reevaluated. In those with persistent or recurrent NGU, the most common organism is Mycoplasma genitalium, especially following treatment with doxycycline. Antimicrobial resistance is noted to be high for M genitalium. [28] There is a reported 31% median cure rate for doxycycline. [29]

The CDC recommends a two-stage approach for treatment for M. genitalium. If M. genitalium resistance testing is available it should be performed, and the results should be used to guide therapy. If M. genitalium resistance testing is not available, the recommended treatment is doxycycline 100 mg orally 2 times/day for 7 days followed by moxifloxacin 400 mg orally once daily for 7 days. Higher doses of azithromycin have not been effective for M. genitalium after azithromycin treatment failures. [4]

European guidelines for the treatment of M. genitalium differ from the CDC and a stepped approach is used [30] :

  • Uncomplicated  M. genitalium infection without macrolide resistance mutations or resistance testing:  Azithromycin 500 mg on day one, then 250 mg on days 2–5 
  • Second-line treatment and treatment for uncomplicated macrolide-resistant  M. genitalium infection:  Moxifloxacin 400 mg for 7 days 
  • Third-line treatment for persistent  M. genitalium infection after azithromycin and moxifloxacin:  Doxycycline or minocycline 100 mg bid for 14 days  or  Pristinamycin 1 g qid for 10 days 
  • Complicated  M. genitalium infection (PID, epididymitis):  Moxifloxacin 400 mg for 14 days.

Trichomonas vaginalis infection should be considered in heterosexual patients with persistent symptoms. In regions where T vaginalis is prevalent, patients with urethritis should be treated empirically with metronidazole 2 g orally in a single dose or tinidazole 2 g orally in a single dose. [4]

See also Urethritis Empiric Therapy and Urethritis Organism-Specific Therapy.



Consider urology consultation in patients with persistent or recurrent NGU after presumptive treatment for GU, NGU, and M genitalium or T vaginalis  [4] .



The most effective strategies for urethritis prevention include measures to reduce STD transmission, since the most common cause of urethritis is infectious in nature. The most reliable way to avoid STD transmission is to abstain from oral, anal, or vaginal intercourse or to remain in a long term, monogamous relationship with an uninfected partner. Male condoms, when used consistently and correctly, reduce the risk of transmission of chlamydial infection, gonorrhea, and trichomoniasis. There are few to no data regarding STD prevention with female condoms, cervical diaphragms, or topical microbicides and spermicides. Nonbarrier contraception, surgical sterilization, or hysterectomy offer no protection against STDs. In cases of noninfectious urethritis, avoid urethral irritants such as perfumed soaps, body washes, lotions, or lubricants and frequent masturbation/sexual intercourse.


Long-Term Monitoring

Only patients who remain symptomatic require follow-up cultures to ensure eradication of infection.  If symptoms persist following adequate treatment, the disease is most likely nongonococcal urethritis (NGU). Prior to improved culture methods and increased awareness of the causes of NGU, symptom recurrences were thought to be psychological in nature. This is usually not the case, and most cases of recurrent NGU are related to persistent chlamydial, ureaplasmal, or mycoplasmal infection. These patients benefit from further treatment previously mentioned. 

Most infections after treatment are due to reinfection by the same or a new partner, stressing the need to educate patients and to treat partners.