Urethritis 

Updated: Dec 18, 2020
Author: Dustin L Whitaker, MD; Chief Editor: Edward David Kim, MD, FACS 

Overview

Practice Essentials

Urethritis is defined as inflammation of the urethra. Although this condition may result from infectious or noninfectious etiologies, the term urethritis is typically reserved to describe urethral inflammation caused by a sexually transmitted disease (STD).[1]

Several organisms can cause infectious urethritis. This condition is normally categorized as either gonococcal urethritis (GU), due to the gram-negative intracellular diplococcus Neisseria gonorrhoeae, or nongonococcal urethritis (NGU). NGU is most commonly due to Chlamydia trachomatis, although the prevalence of Mycoplasma genitalium is on the rise.[2]

Signs and symptoms

Many patients with urethritis, including approximately 25% of those with NGU, are asymptomatic and present to a clinician following partner screening.[3] Up to 75% of women with C trachomatis infection are asymptomatic.

Signs and symptoms in patients with urethritis may include the following:

  • Urethral discharge: May be yellow, green, brown, or tinged with blood; production unrelated to sexual activity

  • Dysuria (in men): Usually localized to the meatus or distal penis, worst during the first morning void, and made worse by alcohol consumption; urinary frequency and urgency are typically absent 

  • Itching/stinging: Sensation of urethral itching or irritation between voids

  • Orchalgia: Pain in the testicles

  • Worsening of symptoms during the menstrual cycle (occasionally).

  • Systemic symptoms (eg, fever, chills, sweats, nausea) are typically absent

See Presentation for more detail.

Diagnosis

Urethritis can usually be diagnosed with a careful history (including social/sexual history) and physical examination. Most patients with urethritis do not appear ill or exhibit systemic signs of infection. The examination should be focused on the abdomen, pelvis, and genitalia.

Examination in male patients with urethritis includes the following:

  • Inspect the underwear for secretions

  • Penis: Examine for skin lesions that may indicate other STDs (eg, condyloma acuminatum, herpes simplex, syphilis); in uncircumcised men, retract the foreskin to assess for lesions and exudate

  • Urethra: Examine the lumen of the distal urethral meatus for lesions, stricture, or obvious urethral discharge; palpate along the urethra for areas of fluctuance, tenderness, or warmth suggestive of abscess or for firmness suggesting foreign body

  • Testes: Examine for evidence of mass or inflammation; palpate the spermatic cord, feeling for swelling, tenderness, or warmth suggestive of orchitis or epididymitis

  • Lymphatics: Check for inguinal adenopathy

  • Prostate: Palpate for tenderness or bogginess suggestive of prostatitis

  • Rectal: During the digital rectal examination, note any perianal lesions

Examine female patients in the lithotomy or frog leg position. Include the following evaluation:

  • Skin: Assess for lesions that may indicate other STDs

  • Urethra: Strip the urethra for any discharge

  • Pelvis: Complete pelvic examination, including the cervix

Testing

Based on the current Center for Disease Control (CDC) guidelines, urethritis can be documented on the basis of any of the following signs or laboratory tests[4] :

  • Mucoid, mucopurulent, or purulent discharge on examination

  • Gram stain of urethral secretions demonstrating ≥2 white blood cells (WBC) per oil immersion field on microscopy

  • Positive leukocyte esterace test from a first-void urine

  • Microscopic examination of sediment from a spun first-void urine demonstrating ≥10 WBC per high power field

All patients with urethritis should be tested for N gonorrhoeae and C trachomatis. Laboratory studies may include the following:

  • Gram stain

  • Endourethral and/or endocervical culture for N gonorrhoeae and C trachomatis

  • Urinalysis: Not used for urethritis diagnosis; can help exclude cystitis or pyelonephritis in cases of dysuria without discharge

  • Nucleic acid–based tests: For C trachomatis and N gonorrhoeae (urine specimens) and other Chlamydia species (endourethral samples)

  • Nucleic acid amplification tests (eg, PCR) are the preferred method for diagnosis of N gonorrhoeae, Chlamydia species

  • Potassium hydroxiKOH preparation: to evaluate for fungal organisms

  • Wet mount preparation: To detect the movement/presence of Trichomonas

  • STD testing for syphilis serology (VDRL) and HIV serology

  • Nasopharyngeal and/or rectal swabs: For gonorrhea screening in men who have sex with men

  • Pregnancy testing: In women who have had unprotected intercourse

Imaging studies

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

Procedures

The following procedures may bre needed in patients with urethritis:

  • Catherization: In cases of urethral trauma; to avoid urinary retention and tamponade urethral bleeding

  • Cystoscopy: In cases when catherization is not possible, for placement of a catheter; to remove foreign body or stone in the urethra

  • Dilation of urethral strictures with Amplatz dilators 

  • Placement of suprapubic tube: In severe cases of urethral trauma that prevent placement of urethral catheters or in the absence of adequate facilities for emergent cystoscopy; temporizing measure to divert urine and relieve patient discomfort

See Workup for more detail.

Management

Symptoms of urethritis spontaneously resolve over time, regardless of treatment. Administer antibiotics that cover both GU and NGU. Regardless of symptoms, administer antibiotics to the following individuals:

  • Patients with positive Gram stain or culture results

  • All sexual partners of the above patients

  • Patients with negative Gram stain results and a history consistent with urethritis who are not likely to return for follow-up and/or are likely to continue transmitting infection

Antibiotics used in the treatment of urethritis include the following:

  • Azithromycin
  • Ceftriaxone
  • Cefixime
  • Gemifloxacin
  • Gentamicin
  • Doxycycline
  • Erythromycin
  • Levofloxacin
  • Ofloxacin
  • Moxifloxacin

See Treatment and Medication for more detail.

Pathophysiology

Urethritis is an inflammatory condition that can be infectious or posttraumatic in nature. Infectious causes of urethritis are typically sexually transmitted and categorized as either GU (ie, due to infections with Neisseria gonorrhoeae) or NGU (eg, due to infections with Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis, Mycoplasma genitalium, or Trichomonas vaginalis). The presence of Gram-negative intracellular diplococci on urethral smear is suggestive of gonococcal urethritis. Gonococcal infection is typically accompanied by chlamydial infection, which accounts for 15%-40% of NGU cases. It is essential to document chlamydial infections due to the need for partner evaluation and treatment to prevent complications from chlamydial infections, especially in female partners.

There has been a notable increase in the incidence of urethritis associated with Mycoplasma genitalium, now the second most common cause of NGU, although there is currently a lack of US Food and Drug Administration (FDA)–approved tests for diagnostic use. This organism can be sexually transmitted, accounts for 15%-25% of NGU cases in the United States and should be suspected in cases of recurrent or persistent urethritis.[2, 5]

Haemophilus species are an increasing cause of NGU, particularly in patients who have unprotected oral sex.[6, 7, 8]  Rare infectious causes of urethritis include lymphogranuloma venereum, herpes simplex virus types 1 and 2, adenovirus, syphilis, mycobacterial infection, Corynebacterium,[9]  and bacterial infections that are typically associated with cystitis (usually gram-negative rods) in the presence of urethral stricture. Other rare but reported causes of urethritis include viral, streptococcal, anaerobic, and meningococcal infections. However, in up to 35% of NGU cases, no pathogen is found.[10]

Posttraumatic urethritis can occur in 2%-20% of patients practicing intermittent catheterization and following instrumentation or foreign body insertion. Urethritis is 10 times more likely to occur with latex catheters than with silicone catheters.

Urethritis may be associated with other infectious conditions, such as the following:

Etiology

Urethritis may be gonococcal, nongonococcal, or mixed.

Gonococcal urethritis (80% of cases) is caused by Neisseria gonorrhoeae, which is a gram-negative intracellular diplococcus. Gonococcal urethritis has a shorter incubation period than nongonococcal urethritis (NGU), and the onset of dysuria and purulent discharge is abrupt.

NGU, which comprises 50% of urethritis cases, has a longer incubation period than gonococcal urethritis, and the onset of either dysuria or, less commonly, a mucopurulent discharge, is subacute. Patients with NGU are much more likely to be asymptomatic than are patients with gonococcal urethritis.

Commonly identified causes of NGU include the following:

  • Chlamydia trachomatis (15-40% of cases)
  • Mycoplasma genitalium (15-20% of cases)
  • Ureaplasma urealyticum
  • Trichomonas vaginalis

The number of fastidious organisms implicated in NGU is increasing and includes several Ureaplasma and Mycoplasma species. T vaginalis is another potential cause of NGU and has a reported high prevalence (20%) among heterosexual men in Africa.[11] Haemophilus species, herpes simplex virus, Epstein-Barr virus, and adenovirus can lead to urethritis in patients who practice oral to penile contact. Enteric bacteria have been implicated in patients who practice insertive anal intercourse. In most patients with NGU, the causative organism cannot be identified. 

Rare cases may be related to lymphogranuloma venereum, herpes simplex, syphilis, mycobacteria, or urinary tract infection with urethral stricture. Other rare but reported causes of NGU include anaerobes, adenovirus, cytomegalovirus, and streptococcus.

Urethritis following catheterization occurs in 2-20% of patients practicing intermittent catheterization and is 10 times more likely to occur with latex catheters than with silicone catheters.

Polymicrobial NGU and cases of urethritis due to both gonococcal infection and nongonococcal factors are possible and can explain some treatment failures. This should also be considered in patients with HIV infection.

Epidemiology

STDs are an unrecognized epidemic within the United States and pose a serious threat to the overall health and economic well-being of the population. Nearly 20 million new STDs occur each year in the US, with an estimated treatment cost of $16 billion dollars annually.[12] Urethritis occurs in 4 million Americans each year.[13]

There is currently a resurgence of various STDs that had previously been on the decline.[14, 15] The incidence of GU steadily declined from 2000 to 2009, but then began intermittently rising. The incidence of NGU is on also the rise. The 2018 Centers for Disease Control and Prevention (CDC) STD Surveillance Report demonstrated an increase in incidence of syphilis, gonorrhea, and chlamydia, the three most commonly reported STDs. Relative to 2017, the incidence of gonorrhea increased by 5% to more than 580,000 cases (the most reported since 1991) and Chlamydia infections increased by 3% to more than 1.7 million cases (the most ever reported to the CDC).[16] These results are summarized in the table below.

Table. Reported Sexually Transmitted Diseases in the United States, 2018 (Open Table in a new window)

Disease Reported Cases Rate per 100,000 people Change relative to 2017
Chlamydia 1,758,668 540 3% increase
Gonorrhea 583,405 179 5% increase
Syphilis 115,045 35 14% increase

Worldwide, approximately 62 million new cases of GU and 89 million new cases of NGU are reported each year.

Urethritis has no racial predilection. However, persons of low socioeconomic class are affected more often than persons of higher socioeconomic class.

Urethritis has no sexual predilection; however, data may be skewed because urethritis is under-recognized in women. Up to 75% of females with the condition can be asymptomatic or may instead present with cystitis, vaginitis, or cervicitis.[17]  Men who have sex with men are at a greater risk for urethritis than are heterosexual males or females in general.

Urethritis may occur in any sexually active person, but incidence is highest among people aged 20-24 years.

Prognosis

All patients with uncomplicated urethritis spontaneously recover with or without treatment.

Complications, such as stricture, stenosis, or abscess formation, are quite rare. Concomitant epididymitis or prostatitis is not uncommon. Increasing evidence shows that genital chlamydial infection in males may predispose to infertility. In addition, both Chlamydia and U urealyticum can impair sperm and adversely affect semen parameters.[18, 19, 20]

Approximately 10%-40% of women with urethritis eventually develop pelvic inflammatory disease (PID), which may subsequently cause infertility and ectopic pregnancy secondary to postinflammatory scar formation in the fallopian tubes. PID can occur even in women with asymptomatic infections.

Children born to mothers with Chlamydia infection may develop conjunctivitis, iritis, otitis media, or pneumonia if exposed to the organism while passing through the birth canal. Performing cesarean delivery in patients with known chlamydial infections and routine treatment of all newborns with anti-chlamydial eyedrops has decreased the incidence of this problem in developed countries.

Disseminated gonococcal infection (DGI) and reactive arthritis develop in fewer than 1% of female patients with urethritis. Reactive arthritis is characterized by NGU, anterior uveitis, and arthritis and is strongly associated with the gene for HLA-B27. Rare but serious complications of DGI include arthritis, meningitis, and endocarditis.

Morbidity due to urethritis in males is less common (1%-2%), typically taking the form of urethral stricture or stenosis due to postinflammatory scar formation. Other potential complications of urethritis in males include prostatitis, acute epididymitis, abscess formation, proctitis, infertility, abnormal semen, DGI, and reactive arthritis.

Mortality rates are minimal in patients with gonococcal urethritis or NGU.

Patient Education

Patient should be told the following about this condition:

  • Refrain from sexual intercourse for one week after starting antibiotic therapy and until all partners are adequately treated.
  • Avoid urethral irritants such as perfumed soaps, body washes, lotions, or lubricants and vigorous or frequent masturbation or sexual intercourse.
  • Limit the number of sexual partners and always use barrier devices, such as condoms, when engaging in intercourse.
  • Infections can spread by oral, anal, or vaginal intercourse.
  • Return for evaluation if experiencing persistent or recurrent symptoms of urethritis.

Educate at-risk patients on how to prevent disease recurrence and educate patients on risks of other sexually-transmitted infections, including HIV.[21]  Instruct patients to avoid the following high-risk behaviors associated with STDs:

  • Intercourse at a young age, which with rare exceptions is associated with multiple sex partners and unprotected intercourse
  • Intercourse with multiple partners
  • Drug use
  • Unprotected sex
  • Intercourse with partners known to have infections

For patient education information, see the Sexual Health Center and Sexually Transmitted Diseases.

 

Presentation

History

Obtaining a careful patient history often helps differentiate between a sexually transmitted disease (STD) and other causes of urethritis. The questions can be quite personal, and the physician should take care to remain objective regarding the patient's sexual history. If the patient is made to feel uncomfortable, they may not be forthcoming with essential information necessary to guide further diagnosis and treatment. This can delay or impede treatment altogether for the patient and their sexual partners, including the chain of partners that may be linked to the patient (eg, partners of partners and so on).

Sexual history

Certain sexual practices may increase or decrease the likelihood of contracting infectious urethritis.

Contraceptive use

Condom use substantially decreases the chance of STD transmission. Other forms of contraception either do not improve or worsen the chance of transmitting infectious urethritis. The use of spermicides may cause a chemical urethritis which can mimic the symptoms of infectious urethritis.

Age at first intercourse

Apart from certain religious groups that encourage marriage and monogamy at an early age, early age at first intercourse correlates with an increased risk of STD.

Number of sexual partners

Individuals with multiple sexual partners are more likely to contract an STD. Long-term monogamous couples are extremely unlikely to contract an STD. A married patient should not be informed of the diagnosis (or possible diagnosis) in the presence of his or her spouse, but the spouse should be treated once the patient has had the opportunity to discuss further with their spouse.

Sexual preference

Men who have sex with men have the highest rate of STDs. They are followed, in order of occurrence rates, by men who have sex with women, women who have sex with men, and women who have sex with women. 

Previous STDs

Patients with a prior history of STDs are at an increased risk of contracting another STD. Concurrent STDs may also occur. A high level of suspicion for more sinister STDs, such as syphilis and HIV infection, should be maintained. In addition, urethritis can increase viral shedding of HIV and can increase the likelihood of transmission.[22]

Symptoms

Many patients, including approximately 25% of those with nongonococcal urethritis (NGU), are asymptomatic and present following partner screening. Up to 75% of women with Chlamydia trachomatis infection are asymptomatic.

The clinician should specifically address the following manifestations:

  • Timing: Symptoms generally begin 4 days to 2 weeks after contact with an infected partner, or the patient may be asymptomatic.

  • Urethral discharge: Fluid may be yellow, green, brown, or tinged with blood, and production is unrelated to sexual activity.

  • Dysuria: Typically localized to the meatus or distal penis, worst during the first morning void, and worsened with alcohol consumption. Urinary frequency and urgency are typically absent. If present, either should suggest prostatitis or cystitis.

  • Itching: A sensation of urethral itching or irritation may persist between voids, and some patients have itching instead of pain or burning.

  • Orchalgia: Men sometimes complain of heaviness in the genitals. Associated pain in the testicles should suggest epididymitis, orchitis, or both.

  • Menstrual cycle: Women occasionally complain of worsening symptoms during menses.

  • Foreign body or instrumentation: The patient should be questioned about recent urethral catheterization or instrumentation, either medical or self-induced (eg, foreign body), which may cause traumatic urethritis.

Systemic symptoms

Systemic symptoms (eg, fever, chills, sweats, nausea) are typically absent but, if present, may suggest disseminated gonococcemia, pyelonephritis, arthritis, conjunctivitis, proctitis, prostatitis, epididymitis or orchitis, pneumonia, otitis media, or reactive arthritis (eg, low back pain, iritis, or rash [characteristically involving the palms of hands and soles of feet]).

Physical Examination

Most patients with urethritis do not appear ill and do not present with signs of sepsis, such as fever, tachycardia, tachypnea, or hypotension. The primary focus of the examination is on the genitalia.

Men

It is best to avoid examination immediately following micturition as urination temporarily washes away discharge and potentially culturable organisms. Since urine culture is an important component of the evaluation, advise the patient to urinate approximately 2 hours before the examination so that culture and examination results are optimal and the patient can comfortably provide a urine specimen after the examination.

Ensure that the patient is standing, completely undressed from the waist down, and that the room is warm and with good lighting. Inspect the underwear for secretions which may yield information.

Examine the patient for skin lesions that may indicate other STDs, such as condyloma acuminatum, herpes simplex, or syphilis. The examiner must retract the foreskin of uncircumcised men to fully examine the penis and urethra.

Examine the lumen of the distal urethral meatus for lesions, stricture, or obvious urethral discharge.

Strip the urethra by gently palpating from the base of the penis to the glans to reveal any urethral discharge. Any discharge should be sampled and sent for analysis and culture. Palpate along the urethra for areas of fluctuance, tenderness, or warmth or for firmness, which may suggest abscess or foreign body, respectively.

Examine the testes for masses or inflammation. Palpate the spermatic cord, examining for swelling, tenderness, or warmth suggestive of orchitis or epididymitis.

Check for inguinal adenopathy.

Palpate the prostate for tenderness or bogginess suggestive of prostatitis. Note any lesion around the external anus during digital rectal exam.

Women

As with male patients, it is best to avoid examination immediately following micturition. Advise the patient to urinate approximately 2 hours before the examination so that culture and examination results are optimal and the patient can comfortably provide a urine specimen after the examination.

The patient should be in the lithotomy or frog leg position.

Inspect the skin for any lesions that may indicate the presence of other STDs.

Strip the urethra by inserting a finger into the anterior vagina and gently palpating forward along the urethra. Any discharge should be sampled and sent for analysis and culture.

Follow the urethral examination with a complete pelvic examination, including cervical cultures.

 

DDx

Diagnostic Considerations

Other problems to be considered in the differential diagnosis include the following:

  • Trichomonal vaginitis
  • Candidal vaginitis
  • Alcohol ingestion
  • Contact dermatitis secondary to spermicides, soaps, perfumes, etc
  • Guilt over sexual behavior likely to be perceived as deviant
  • Guilt over infidelity
  • Dried semen mistaken for discharge
  • Stevens-Johnson syndrome
  • Foreign body
  • Fungal infections of the genitourinary tract

Differential Diagnoses

 

Workup

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
  • 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 trachomatis. 

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

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

Catheterization

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.

Cystoscopy

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.

 

Treatment

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.[15]  

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.[26]

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[26] : ceftriaxone 250 mg IM, cefixime 400 mg orally, or spectinomycin 2 g IM.

For treatment of NGU, the CDC currently recommends azithromycin, 1 g orally in a single dose, or doxycycline, 100 mg orally twice a day for 7 days.[15, 4] Alternative regimens include any of the following: erythromycin base 500 mg orally four times a day for 7 days, erythromycin ethylsuccinate 800 mg orally four times a day for 7 days, levofloxacin 500 mg orally once daily for 7 days, or ofloxacin 300 mg orally twice a day for 7 days.

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.[27] There is a reported 31% median cure rate for doxycycline.[28] . Men in whom a doxycyline regimen fails should be treated with azithromycin, 1 g orally in a single dose per CDC recommendations. This regimen has historically been reported to have a cure rate of 85%, although more recent studies suggest a drop to 40%.[29] European guidelines differ in their treatment recommendations given these trends and suggest a 2- to 5-day course of azithromycin for the treatment of M genitalium in the absence of macrolide resistance.[30]  If azithromycin fails, treatment consists of moxifloxacin 400 mg once daily for 7 days, as studies have shown this dosage is highly effective against M genitalium.[4]

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.

Consultations

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

Prevention

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.

 

Medication

Medication Summary

Administer antibiotics to patients who meet diagnostic criteria for infectious urethritis. Treat all sexual partners of those patients, regardless of symptoms. In patients with a negative Gram stain but history concerning for urethritis, treat empirically if they are at high risk for being noncompliant with follow-up and/or are likely to continue transmitting infection (eg, commercial sex worker, intravenous drug user, homeless person). The latter group may best be served with single-dose therapies.

Antibiotics

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.[21]

The antimicrobial options in the treatment of gonococcal urethritis (GU) include IM ceftriaxone, oral cefixime, oral azithromycin, oral gemifloxacin, and IM gentamicin. Chlamydia trachomatis is the most common cause of nongonococcal urethritis (NGU), and azithromycin and doxycycline have been proven equally efficacious in treatment, although azithromycin is superior to doxycycline in treating Mycoplasma genitalium, the second most common cause of NGU.

Alternative regimens for treating NGU include erythromycin, levofloxacin, and ofloxacin. Moxifloxacin may be used to treat persistent or recurrent NGU. Combinations of probenecid with penicillin, amoxicillin, or ampicillin are no longer used because of resistance. 

Patients with proven GU should be empirically treated for C trachomatis infection. Empiric treatment is less expensive than culture in any population whose coinfection rate is at least 10%. Single-dose empiric treatments offer an advantage in patients who are noncompliant or unlikely to return for follow-up. Single-dose regimens include azithromycin for C trachomatis and ceftriaxone, cefixime, gemifloxacin, or gentamicin for Neisseria gonorrhea.

A single dose of metronidazole plus a 7-day course of erythromycin is recommended for NGU recurrence. Antibiotic therapy is recommended for affected individuals and sexual partners of individuals with documented trichomonal infection, even if asymptomatic.

Fluoroquinolones

Ofloxacin (Floxin)

Levofloxacin (Levaquin, Levofloxacin Systemic)

Moxifloxacin (Avelox, Moxifloxacin Systemic)

Gemifloxacin (Factive)

Cephalosporins, 3rd Generation

Ceftriaxone (Rocephin)

Cefixime (Suprax)

Tetracyclines

Doxycycline (Vibramycin)

Macrolides

Azithromycin (Zithromax)

Erythromycin ethylsuccinate (E.E.S., EryPed)

Aminoglycosides

Gentamicin

 

Questions & Answers

Overview

What is urethritis?

What are the signs and symptoms of urethritis?

What is included in the physical exam of male patients with urethritis?

What is included in the physical exam of female patients with urethritis?

How is urethritis diagnosed?

Which lab tests are performed in the diagnosis of urethritis?

What is the role of imaging studies in the diagnosis of urethritis?

Which procedures are performed in the management of urethritis?

When are antibiotics indicated in the treatment of urethritis?

What antibiotics are used in the treatment of urethritis?

What is the pathophysiology of urethritis?

Which infectious syndromes are associated with urethritis?

What are the causes of urethritis?

What are the causes of nongonococcal urethritis (NGU)?

What is the prevalence of urethritis in the US?

What is the global prevalence of urethritis?

Which patient groups have the highest prevalence of urethritis?

What is the prognosis of urethritis?

What information about urethritis should patients be given?

Presentation

What is the focus of patient history in the diagnosis of urethritis?

Which factors related to STD risk increase the risk for secondary urethritis?

How common is asymptomatic urethritis?

Which clinical history findings are characteristic of urethritis?

What is the focus of the physical exam in patients with suspected urethritis?

What is included in the physical exam of male patients with suspected urethritis?

What is included in the physical exam of female patients with suspected urethritis?

DDX

Which conditions should be included in the differential diagnoses of urethritis?

What are the differential diagnoses for Urethritis?

Workup

How is urethritis diagnosed?

What is the role of Gram stain in the workup of urethritis?

What is the role of urethral cultures in the workup of urethritis?

What is the role of urine studies in the workup of urethritis?

What is the role of nucleic acid amplification tests (NAATs) in the workup of urethritis?

Which lab tests may be beneficial in the evaluation of urethritis?

What is the role of imaging studies in the workup of urethritis?

When is catheterization indicated in the workup of urethritis?

When is cystoscopy indicated in the workup of urethritis?

What is the role of dilators in the workup of urethritis?

When is suprapubic tube placement indicated in the workup of urethritis?

Treatment

How is urethritis treated?

How is gonococcal urethritis treated?

Which antibiotics are used for the treatment of NGU?

How are persistent symptoms of urethritis managed?

When is consultation with a urologist indicated in the treatment of urethritis?

How is urethritis prevented?

What is included in long-term monitoring of patients treated for urethritis?

Medications

What is the role of antibiotics in the treatment of urethritis?

Which medications in the drug class Antibiotics are used in the treatment of Urethritis?

Which medications in the drug class Aminoglycosides are used in the treatment of Urethritis?

Which medications in the drug class Macrolides are used in the treatment of Urethritis?

Which medications in the drug class Tetracyclines are used in the treatment of Urethritis?

Which medications in the drug class Cephalosporins, 3rd Generation are used in the treatment of Urethritis?

Which medications in the drug class Fluoroquinolones are used in the treatment of Urethritis?