Urethritis Workup

Updated: Sep 06, 2023
  • Author: Dustin L Whitaker, MD; Chief Editor: Edward David Kim, MD, FACS  more...
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Laboratory Studies

Previously, urethritis was diagnosed based on Gram stain of urethral discharge demonstrating ≥ 5 white blood cells (WBC) per high power field (hpf). More recent studies suggest that utilizing a threshold of ≥ 5 WBC hpf could miss a significant proportion of infections due to Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma genitalium. [23, 24] According to the current Centers for Disease Control and Prevention (CDC) guidelines, urethritis can be documented on the basis of any of the following signs or laboratory test results [4] :

  • Mucoid, mucopurulent, or purulent discharge on examination
  • Gram stain of urethral secretions demonstrating ≥ 2 WBC per oil immersion field on microscopy
  • The microscopy diagnostic cutoff might vary, depending on background prevalence (≥2 WBCs/high power field [HPF] in high-prevalence settings [STI clinics] or ≥5 WBCs/HPF in lower-prevalence settings).
  • Positive leukocyte esterace test from a first-void urine
  • Microscopic examination of sediment from a spun first-void urine demonstrating ≥ 10 WBC/hpf

All patients with urethritis should be tested for N gonorrhoeae and C trachomatisM. genitalium testing should be performed for men who have persistent or recurrent symptoms after initial empiric treatment. Testing for T. vaginalis should be considered in areas or among populations with high prevalence, in cases where a partner is known to be infected, or for men who have persistent or recurrent symptoms after initial empiric treatment. [4]

Gram stain

Traditionally, treatment was based on Gram stain results. Patients with gram-negative intracellular diplococci on urethral smear received treatment for gonococcal urethritis, and those without gram-negative intracellular diplococci received treatment for nongonococcal urethritis (NGU). Because current recommendations suggest concomitant treatment for both, and with the success of nucleic acid amplification tests (NAATs), a Gram stain may be unnecessary. Of note, the sensitivity of urethral Gram stain is highly dependent on the method of collection and the experience of the provider. A negative Gram stain does not rule out gonococcal urethritis. 

Urethral culture for N gonorrhoeae and C trachomatis

Endourethral culture (obtained by gently inserting a malleable cotton-tipped swab 1-2 cm into the urethra), rather than culture of the expressible discharge, is necessary to test for C trachomatis infection. Endocervical cultures should be obtained in women.

This culture may be a useful screening tool for penicillinase-producing N gonorrhoeae or chromosomally mediated resistance to multiple antibiotics. However, the results do not influence the initial antibiotic therapy, and performing this screening may not be cost-effective. Cultures for N gonorrhoeae should be obtained in cases of sexual assault, developing antimicrobial resistance, or suspected gonorrhea treatment failures. 

Urine studies

Urinalysis is not a useful test in patients with urethritis, except for helping exclude cystitis or pyelonephritis, which may be necessary in cases of dysuria without discharge. Patients with gonococcal urethritis may have leukocytes in a first-void urine specimen and fewer or none in a midstream specimen. More than 30% of patients with NGU do not have leukocytes in urine specimens.

Many nucleic acid–based tests for C trachomatis and N gonorrhoeae can be performed on urine specimens (see below). These require a first-voided specimen. For Chlamydia species, endourethral samples are more accurate.

Nucleic acid amplification tests

Polymerase chain reaction (PCR) assays are available for gonococcal urethritis and Chlamydia infection. NAATs are also available for Mycoplasma species, Ureaplasma species, and Trichomonas vaginalis, but these are not recommended, as they are expensive and do not alter the choice of treatment.

NAATs are the preferred test for both C trachomatis and N gonorrhoeae due to their higher sensitivity and specificity. NAATs can be performed on urethral swabs or first-void urine samples. In males, first-void urine is the preferred specimen for NAATs. To prevent false-negative findings, obtain urethral swabs at least 2 hours after micturition using a calcium-alginate swab on a non-wooden stick inserted at least 1 cm in depth. If patients meet diagnostic criteria for urethritis, but Gram stain is unavailable or inconclusive, administer NAAT testing for C trachomatis and N gonorrhoeae. 

DNA-based tests, unlike culture, do not allow for antibiotic susceptibility testing, but this is unnecessary in most patients as the initial antibiotic therapy will be unchanged.

Other tests

The following additional tests may be considered:

  • Potassium hydroxide (KOH) preparation: This is used to evaluate for fungal organisms
  • Wet preparation: Secretions reveal the movement of trichomonal organisms, if present
  • Sexually transmitted disease (STD) testing: Patients with urethritis should be counseled about the risk for more serious STDs and should be offered syphilis serology (Venereal Disease Research Laboratory [VDRL] test or Rapid Plasma Reagin [RPR] test) and HIV serology. Men who receive a diagnosis of NGU should be tested for HIV and syphilis [4]
  • Nasopharyngeal and/or rectal swabs: Men who have sex with men (and perhaps other patients) should undergo gonorrhea screening with nasopharyngeal and/or rectal swabs; validation of NAATs for these specimens is still in progress [25]
  • Pregnancy testing: Women who have had unprotected intercourse should be offered pregnancy testing

Reactive arthritis is diagnosed on the basis of the presence of NGU and clinical findings of uveitis and arthritis. HLA-B27 testing is of limited value. More readily available laboratory findings, such as elevated erythrocyte sedimentation rate (ESR) in the absence of rheumatoid factor, may be helpful. 


Imaging Studies

Imaging studies, specifically retrograde urethrography, are unnecessary in patients with urethritis, except in cases of trauma or possible foreign body insertion.



Procedures such as urethral catheterization and cystoscopy may be useful, especially in patients with urethral trauma.


In cases of urethral trauma, urethral catheter placement can hold the urethra open to avoid urinary retention caused by edema or a flap of elevated mucosa. The catheter also serves to tamponade urethral bleeding.


When urethral catheter placement is not possible after urethral trauma, careful negotiation of the urethra with a flexible cystoscope can allow passage of a guidewire, over which a Councill tip urethral catheter can be placed. This can generally be performed in the emergency department or outpatient clinic with local anesthesia (lidocaine jelly). However, if not easily accomplished on the initial attempt, this procedure should be aborted to avoid further urethral trauma, and a suprapubic catheter should be placed.

A foreign body or stone in the urethra, which may mimic urethritis, can be removed cystoscopically. Unless the object is very small and very distal, this procedure probably should be undertaken in the operating suite while the patient is under anesthesia. A rigid cystoscope with a larger lumen sheath and working port allows utilization of more secure endoscopic graspers. The object can often be removed through the large lumen of the cystoscope sheath, rather than pulling it through the distal urethra (which may cause further trauma).

Urethral dilators (Amplatz)

Urethral dilation via Amplatz dilators can also be used by experienced urologists but is used less frequently in cases of urethral trauma because of the wide availability of flexible cystoscopes. In addition, this technique can lead to more severe urethral trauma if not used correctly.

Suprapubic catheter placement

With more severe urethral trauma that prevents urethral catheter placement or inadequate facilities for emergent cystoscopy in patients with urethral obstruction due to trauma or foreign bodies, a suprapubic catheter is an excellent temporizing measure to divert urine and relieve patient discomfort until definitive therapy can be undertaken.