Urethritis is a well-defined clinical syndrome manifested by dysuria, a urethral discharge, or both.

Gonococcal urethritis

GCU

• Urethritis commonly is divided into two major categories based on etiology: Gonococcal urethritis (GCU, Neisseria gonorrhoeae spp.) and nongonococcal urethritis (NGU, all other pathogens, most commonly Chlamydia trachomatis).
• This differentiation is based historically on N. gonorrhoeae’s easy visualization on Gram stain as gram-negative, kidney-shaped diplococci.
• In the U.S., rates of gonorrheal urethritis are rising; however, the incidence varies greatly based on race and geography; the prevalence of GCU is disproportionately higher in the South and among Black, non-Hispanic men. The urethra is the most common site of infection in all men.

• Symptoms of GCU: Dysuria is the most common chief complaint in patients with GCU, which is often accompanied by discharge and pruritus. Acute-onset purulent discharge is a hallmark of this infection. Additionally, meatal edema and urethral tenderness to palpation may occur. Approximately 5% to 10% of patients with GCU remain asymptomatic.
• GCU may spread to other parts of the genitourinary system. Prostatic involvement can cause urinary frequency, urgency, and nocturia and may present with mucopurulent discharge. Epididymal involvement can result in unilateral testicular pain and edema.
• Time frame: The incubation period of GCU is variable but is commonly 4 to 7 days. Without treatment, urethritis will persist for 3 to 7 wk, with 95% of men becoming asymptomatic after 3 mo.
• Complications: Periurethritis leading to urethral stenosis can occur. Additionally, disseminated infection can lead to tenosynovitis and arthritis. Rarely, hepatitis, myocarditis, endocarditis, and meningitis can occur.

• NGU
• Herpes simplex virus

• Urethritis is diagnosed when a symptomatic male has any of the following characteristics:
  1. Mucopurulent/purulent discharge on examination
  2. Urethral swab showing:
     1. ≥2 WBCs per field in high-prevalence settings or ≥5 WBCs per field in lower prevalence settings
     2. Gram-negative diplococci seen within WBCs
• Urethritis can be diagnosed by culture or by NAATs.¹ The performance of NAATs with respect to overall sensitivity, specificity, and ease of specimen transport is better than that of any of the other tests available for the diagnosis of chlamydial and gonococcal infections. NAATs should be used as first line to detect chlamydia and gonorrhea, except in cases of child sexual assault, rectal and oropharyngeal infections in prepubescent girls, and when evaluating a potential gonorrhea treatment failure, in which case culture and susceptibility testing might be required.
• Of note, a presumptive diagnosis can be made without the earlier diagnostic criteria for males who are at high risk for sexually transmitted infections (i.e., more than one partner and >25 yr) and who are unlikely to return for follow-up. In these patients, empirical treatment to cover both gonococcal and nongonococcal infections can be given before the results of a nucleic acid amplification test (NAAT).
• Similarly, when in-person testing is not feasible in situations such as the COVID-19 pandemic, sexually active patients with symptoms consistent with urethritis should be treated with a regimen active against gonorrhea. (Dear Colleague Letter: Providing effective care and prevention when facility-based services and in-person patient-clinician contact is limited, 2020).
• If Gram staining is available, it is indicated and should be performed with modified Thayer-Martin media, as this helps differentiate GCU from NGU.
• NAATs have largely replaced culture in many health care settings. They are not more sensitive than culture for detecting N. gonorrhoeae in cervical or urethral specimens; however, they have specificities of >99% and retain sensitivity when used to test first-catch urine.
• For culture and susceptibility testing: Rayon, Dacron, or calcium alginate tips with plastic or wire shafts should be used (not cotton-tipped swabs, which are bactericidal). A swab of the urethra should be performed within 2 to 4 hr after voiding to prevent bacterial washout with urination. Collect cultures of the pharynx and rectum when indicated for concomitant Chlamydia testing on all patients.
• Concomitant serologic testing for syphilis and HIV infections should be offered to all patients.

It is imperative to appropriately counsel patients on the avoidance of intercourse or use of barrier protection until a cure has been obtained and sexual partners have been evaluated. Once treated, patients should be advised to abstain from sex for 7 days.

In cases of suspected cephalosporin treatment failure, clinicians should obtain relevant clinical specimens for culture and antimicrobial susceptibility testing, consult an infectious disease specialist or STD clinical expert (www.stdccn.org/) for guidance in clinical management, and report the case to the Centers for Disease Control and Prevention (CDC) through state and local public health authorities within 24 hr. Health departments should prioritize notification and culture evaluation for the patient’s sex partner(s) from the preceding 60 days for those with suspected cephalosporin treatment failure or persons whose gonococcal isolates demonstrate reduced susceptibility to cephalosporins.

A test of cure (repeat testing 1 to 3 wk after initial treatment) is unnecessary for persons with uncomplicated GCU treated with any of the recommended or alternative regimens. However, for persons with pharyngeal gonorrhea, a test of cure is recommended, using culture or NAATs 7 to 14 days after initial treatment, regardless of the treatment regimen.

Alternatively, repeat testing 3 mo after treatment is recommended for all persons diagnosed with GCU, regardless of treatment, because reinfections rates are so high: Reinfection within 12 mo ranges from 7% to 12% among persons previously treated for gonorrhea. If retesting at 3 mo is not possible, clinicians should retest within 12 mo after initial treatment.

• Reinfection is the most common cause of recurrence.
• Repeat swab and culture of the urethra, pharynx, and rectum (where applicable) are mandatory.
• Persistence of N. gonorrhoeae by smear or culture requires treatment for N. gonorrhoeae.
• Postgonococcal urethritis (PGU): Persistence of polymorphonuclear cells (PMNs) in the absence of gram-negative intracellular diplococci. This occurs when GCU is treated with a regimen that is ineffective against coincident nongonococcal infection; it represents NGU after GCU and should be treated as such.

• Partner notification: The names and contact information of sexual partners should be gathered at the time of diagnosis and referred to the health department, or the patient can notify the contact directly.
• Expedited partner treatment is recommended by the CDC and is approved in most states. This consists of giving prescriptions to the infected patient for their partner(s) who has not been evaluated by a physician and for whom health department partner-management strategies are impractical or unavailable.²
• On examination of the urethral smear, the presence of small numbers of PMNs provides objective evidence of urethritis. The complete absence of PMNs on a urethral smear argues against urethritis. If in addition to the PMNs there are gram-negative, intracellular diplococci, the diagnosis of gonorrhea is established.

Gonococcal Urethritis (Patient Information)

Gonorrhea (Related Key Topic)