Why won’t my urethritis go away?

Recurrent or persistent urethritis—often described as “urethritis that won’t go away”—can be frustrating and concerning, but it’s not uncommon. Several factors may contribute to treatment failure or recurrence. First, the causative pathogen must be correctly identified: while *Chlamydia trachomatis* and *Neisseria gonorrhoeae* are the most frequent bacterial causes, other organisms—including *Mycoplasma genitalium*, *Trichomonas vaginalis*, and even certain viruses or non-infectious triggers (e.g., chemical irritation, trauma, or autoimmune conditions)—can mimic or cause chronic urethral inflammation. Inadequate or inappropriate antibiotic therapy—such as using a narrow-spectrum agent when a broader one is needed, or failing to cover *M. genitalium*, which is increasingly resistant to azithromycin—is a common reason for persistence.

Additionally, reinfection is a major contributor, especially in sexually active individuals who resume intercourse before both partners complete treatment or without consistent condom use. Asymptomatic partners may unknowingly harbor and transmit the infection. Other considerations include poor medication adherence, pharmacokinetic issues (e.g., insufficient drug concentration in urethral tissue), or anatomical factors like urethral strictures or diverticula that harbor biofilms and impede antibiotic penetration. Rarely, noninfectious etiologies—such as urethral syndrome, interstitial cystitis, or lichen sclerosus—must be evaluated, particularly when cultures and nucleic acid amplification tests (NAATs) remain negative despite symptoms.

A thorough reevaluation is essential: this includes detailed sexual history, physical examination, repeat NAAT testing for *C. trachomatis*, *N. gonorrhoeae*, *M. genitalium*, and *T. vaginalis*, and—if indicated—urethral swab culture, urine cytology, or referral to urology for cystourethroscopy. Treatment should be tailored based on test results and local resistance patterns; for example, *M. genitalium* infection often requires moxifloxacin or pristinamycin if azithromycin fails. Partner notification, treatment, and abstinence until both partners complete therapy are critical components of management. If symptoms persist despite appropriate antimicrobial therapy and partner management, further workup for noninfectious causes is warranted.