Urethritis medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2]Sujit Routray, M.D. [3]

Medical Therapy

Treatment should be initiated as soon as possible after diagnosis.

Pharmacotherapy

A variety of drugs may be prescribed based on the cause of the patient's urethritis. Some examples of medications based on causes include:

• Clotrimazole (Mycelex) - Trichomonas
• Doxycycline (Vibramycin) - Chlamydia
• Fluconazole (Diflucan) - Monilial
• Metronidazole (Flagyl) - Trichomonas
• Nitrofurantoin - Bacterial Infection
• Nystatin (Mycostatin) - Monilial
• Co-trimoxazole, which is a combination of Sulfamethoxazole and Trimethoprim in a ratio of 5 to 1 (Septrin, Bactrim) - Bacterial Infection

Antimicrobial Therapy

• 1. Nongonococcal Urethritis

• Preferred regimen: Azithromycin 1 g PO in a single dose OR Doxycycline 100 mg PO bid for 7 days
• Alternative regimen (1): Erythromycin base 500 mg PO qid for 7 days
• Alternative regimen (2): Erythromycin ethylsuccinate 800 mg PO qid for 7 days
• Alternative regimen (3): Levofloxacin 500 mg PO qd for 7 days
• Alternative regimen (4): Ofloxacin 300 mg PO bid for 7 days

• 2. Gonococcal Urethritis

• Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1 g PO in a single dose
• Alternative regimen: Cefixime 400 mg PO in a single dose AND Azithromycin 1 g PO in a single dose (if ceftriaxone is not available)

• 3. Recurrent and Persistent Urethritis

• Preferred regimen: Metronidazole 2 g PO in a single dose OR Tinidazole 2 g PO in a single dose AND Azithromycin 1 g PO in a single dose for 7 days

Follow-Up

Patients should be instructed to return for evaluation if symptoms persist or recur after completion of therapy. Symptoms alone, without documentation of signs or laboratory evidence of urethral inflammation, are not a sufficient basis for retreatment. Providers should be alert to the possibility of chronic prostatitis/chronic pelvic pain syndrome in male patients experiencing persistent pain (perineal, penile, or pelvic), discomfort, irritative voiding symptoms, pain during or after ejaculation, or new-onset premature ejaculation lasting for >3 months.

Unless a patient’s symptoms persist or therapeutic noncompliance or reinfection is suspected by the provider, a test-of-cure (i.e., repeat testing 3–4 weeks after completing therapy) is not recommended for persons with documented chlamydia or gonococcal infections who have received treatment with recommended or alterative regimens. However, because men with documented chlamydial or gonococcal infections have a high rate of reinfection within 6 months after treatment (251,252), repeat testing of all men diagnosed with chlamydia or gonorrhea is recommended 3–6 months after treatment, regardless of whether patients believe that their sex partners were treated (251).

Partner Referral

A specific diagnosis might facilitate partner referral. Therefore, testing for gonorrhea and chlamydia is encouraged. Because a substantial proportion of female partners of males with nonchlamydial NGU are infected with chlamydia, partner management is recommended for males with NGU regardless of whether a specific etiology is identified. All sex partners within the preceding 60 days should be referred for evaluation, testing, and empiric treatment with a drug regimen effective against chlamydia. Expedited partner treatment and patient referral are alternative approaches to treating partners (71).

Recurrent Urethritis

Objective signs of urethritis should be present before the initiation of antimicrobial therapy. In persons who have persistent symptoms after treatment without objective signs of urethritis, the value of extending the duration of antimicrobials has not been demonstrated. Persons who have persistent or recurrent urethritis can be retreated with the initial regimen if they did not comply with the treatment regimen or if they were reexposed to an untreated sex partner. Persistent urethritis after doxycycline treatment might be caused by doxycycline-resistant U. urealyticum orM. genitalium. T. vaginalis is also known to cause urethritis in men; a urethral swab, first void urine, or semen for culture or a NAAT (PCR or TMA) on a urethral swab or urine can be performed. If compliant with the initial regimen and re-exposure can be excluded, the following regimen is recommended while awaiting the results of the diagnostic tests.

Recurrent Non-gonococal Urethritis Preferred Regimen ▸ Metronidazole 2 gm po single dose PLUS ▸ Azithromycin 1 gm po x 1 dose Alternative Regimen ▸ Tinidazole 2 gm po x 1 dose PLUS ▸ Azithromycin 1 gm po x 1 dose

Studies involving a limited number of patients who experienced NGU treatment failures have demonstrated that Moxifloxacin 400 mg orally once daily for 7 days is highly effective against M. genitalium (253,254). Men with a low probability of T. vaginalis (e.g., MSM) are unlikely to benefit from the addition of metronidazole or tinidazole.

Urologic examinations usually do not reveal a specific etiology for urethritis. A four-glass Meares-Stamey lower-urinary-tract localization procedure (or four-glass test) might be helpful in localizing pathogens to the prostate (255). A substantial proportion of men with chronic nonbacterial prostatitis/chronic pelvic pain syndrome have evidence of urethral inflammation without any identifiable microbial pathogens. Estimates vary considerably depending on the source and sensitivity of the assay, but one study demonstrated that in 50% of men with this syndrome, ≥5 WBCs per high-power field were detected in expressed prostatic secretions (256). Referral to a urologist should be considered for men who experience pain for more than 3 months within a 6-month period.

If men require treatment with a new antibiotic regimen for persistent urethritis and a sexually transmitted agent is the suspected cause, all partners in the past 60 days before the initial diagnosis and any interim partners should be referred for evaluation and appropriate treatment.

Special Considerations

HIV Infection

Gonococcal urethritis, chlamydial urethritis, and nongonococcal, nonchlamydial urethritis might facilitate HIV transmission. Patients who have NGU and also are infected with HIV should receive the same treatment regimen as those who are HIV negative.