AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Urethritis is an inflammation of the urethra caused by infection. Although irritation of the urethra may occur in a variety of clinical conditions, the term urethritis is typically reserved to describe a syndrome of sexually transmitted diseases (STDs); more specifically, the 2 terms that describe this condition are gonococcal urethritis (GU) and nongonococcal urethritis (NGU).

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 (ie, due to infections with Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis, Mycoplasma genitalium, or Trichomonas vaginalis).

Rare infectious causes of urethritis include lymphogranuloma venereum, herpes genitalis, syphilis, mycobacteria, and typical bacteria (usually gram-negative rods) associated with cystitis in the presence of urethral stricture. Other rare but reported causes of urethritis include viral, streptococcus, anaerobes, and meningococcus.

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 syndromes such as epididymitis, orchitis, prostatitis, proctitis, Reiter syndrome, iritis, pneumonia, otitis media, or urinary tract infection.

Frequency

United States

Urethritis occurs in 4 million Americans each year. The incidence of GU is estimated at over 700,000 new cases annually, and the incidence of NGU is approximately 3 million new cases annually. Both infections are significantly underreported. The incidence of GU has declined steadily since 2000, and the incidence of NGU is increasing. NGU incidence is higher in the summer months compared to other months of the year.

International

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

Mortality/Morbidity

• Morbidity occurs in 10-40% of women because of pelvic inflammatory disease (PID). This disease may subsequently cause infertility and ectopic pregnancy because of postinflammatory scar formation in the fallopian tubes. PID can occur even in women with asymptomatic infections. Children born to mothers infected with Chlamydia species 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 antichlamydial eyedrops has decreased the incidence of this problem in developed countries. Disseminated gonococcal infection (DGI) and Reiter syndrome occur in fewer than 1% of female patients.
• Morbidity occurs in 1-2% of male patients with urethritis. These patients most commonly develop urethral stricture or stenosis because of postinflammatory scar formation. Other potential complications include prostatitis, acute epididymitis, abscess formation, proctitis, infertility, abnormal semen, DGI, and Reiter syndrome.
• Reiter syndrome consists of nongonococcal urethritis, anterior uveitis, and reactive arthritis and is strongly associated with the gene for HLA-B27. Rare but serious complications of disseminated gonococcal infection include arthritis, meningitis, and endocarditis. Mortality is minimal in patients with either GU or NGU.

Race

• No racial predilection exists; however, persons of low socioeconomic class are affected more often than persons of higher socioeconomic class.

Sex

• Urethritis occurs equally in males and females; however, data may be skewed because urethritis is underrecognized in women. Up to 75% of females can be asymptomatic or may instead present with cystitis, vaginitis, or cervicitis. Urethritis is more common in homosexual males than heterosexual males, heterosexual females, or homosexual females.

Age

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

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Obtaining a careful patient history often helps differentiate between an STD and other causes of urethritis. The questions can be quite personal, and the physician should take care to not appear disgusted, amused, or judgmental regarding the patient's sexual history. If patients feel uncomfortable, they may not be forthcoming with essential information that may be helpful in their treatment or the treatment of any sexual partners, ie, 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 urethritis secondary to an STD.
• • Contraceptive use: Using condoms helps substantially decrease the chance of STD transmission. Other types of birth control do not improve or worsen the chance of transmitting urethritis. The use of spermicides may cause a chemical urethritis, with associated dysuria findings that mimic those of infectious urethritis.
  • Age at first intercourse: With the exception of some religious groups who encourage marriage and monogamy at an early age, a younger age at first intercourse is correlated with increased risk of contracting STDs.
  • Number of partners: Individuals with multiple partners are more likely to have contracted 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 explain the situation.
  • Sexual preference: Homosexual men have the highest rate of STDs. They are followed, in order of occurrence rates, by heterosexual men, heterosexual women, and homosexual women.
  • Previous STDs: Patients with a prior history of STDs have a higher likelihood of contracting another STD. Concurrent STDs also may occur. A high level of suspicion for other more sinister STDs, such as syphilis and HIV infection, should be maintained.
• Symptoms: Many patients, including approximately 25% of those with NGU, are asymptomatic and present following partner screening. Up to 75% of women with C trachomatis infection are asymptomatic.
• • 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: Dysuria is 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. 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). These procedures 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, low back pain (ie, Reiter syndrome), iritis, or rash (characteristically involving the palms of hands and soles of feet).

Physical

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

• Men
• • The best plan is to avoid examining the patient immediately after micturition because urination temporarily washes away discharge and potentially culturable organisms. Because 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, is completely undressed, and that the room is warm and has good lighting. When the patient is undressed, inspecting the underwear for secretions may yield additional 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. Lesions and exudate may be hiding beneath.
  • Examine the lumen of the distal urethral meatus for lesions, stricture, or obvious urethral discharge.
  • Strip the urethra by gently milking from the base of the penis to the glans. Any discharge may then be seen exuding from the urethral meatus. Palpate along the urethra for areas of fluctuance, tenderness, or warmth suggestive of abscess or for firmness suggestive of foreign body.
  • Examine the testes for evidence of mass or inflammation. Palpate the spermatic cord, looking for swelling, tenderness, or warmth suggestive of orchitis or epididymitis.
  • Check for inguinal adenopathy.
  • Palpate the prostate for tenderness or bogginess suggestive of prostatitis. During the digital rectal examination, note any lesions around the anus.
• Women
• • The best plan is to avoid examining the patient immediately after micturition because urination temporarily washes away discharge and potentially culturable organisms. Because 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.
  • The patient should be in the lithotomy 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 stroking forward along the urethra. Any discharge should be sampled for examination.
  • Follow the urethral examination with a complete pelvic examination, including cervical cultures.
• General: Fever, palmar rash, joint tenderness, and conjunctivitis are indications of systemic disease.

Causes

• Gonococcal urethritis
• • GU (80% of cases) is caused by N gonorrhoeae, which is a gram-negative intracellular diplococcus.
  • Patients with GU have a shorter incubation period compared to those with NGU, and the onset of dysuria and purulent discharge is abrupt.
• Nongonococcal urethritis
• • Patients with NGU (50% of cases) have a longer incubation period compared to those with GU, 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 patients with GU.
  • NGU is caused by C trachomatis (15-55% of cases), U urealyticum (40-60% of cases), M hominis (5-10% of cases), and T vaginalis ( <5% of cases). The number of fastidious organisms implicated in NGU is increasing and includes several Ureaplasma and Mycoplasma species. The causative organism cannot be identified in most patients with NGU.
  • 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.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Trichomonal vaginitis
Candidal vaginitis
Alcohol ingestion
Contact dermatitis secondary to spermicides
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

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Urethritis can be diagnosed based on the presence of one or more of the following: (1) a mucopurulent or purulent urethral discharge, (2) urethral smear that demonstrates at least 5 leukocytes per oil immersion field on microscopy, and (3) first-voided urine specimen that demonstrates leukocyte esterase on dipstick test or at least 10 white blood cells (WBCs) per high-power field on microscopy.
• All patients with urethritis should be tested for Neisseria gonorrhea and C trachomatis.
• Gram stain
• • Traditionally, treatment was based on Gram stain results. Those patients with gram-negative intracellular diplococci on urethral smear received treatment for GC, and those patients without gram-negative intracellular diplococci received treatment for NGU.
  • Because current recommendations suggest patients receive concomitant treatment for both, and with the success of nucleic acid amplification tests (NAATs), performing a Gram stain may not be necessary.
• 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 for determining if C trachomatis infection is present. Endocervical cultures should also 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.
• Urine
• • Urinalysis is not a useful test for patients with urethritis, except for helping exclude cystitis or pyelonephritis, which may be necessary in cases of dysuria without discharge. Patients with GU 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 gonorrhea 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 assays are available for GC and Chlamydia species. NAATs are also available for Mycoplasma species, Ureaplasma species, and T vaginalis, but these are not recommended, as they are expensive and do not alter the choice of treatment.
  • NAATs are the preferred test for Chlamydia and are more sensitive than traditional culture methods. Chlamydia DNA probe results are 60-70% sensitive and nearly 100% specific. Obtain samples on swabs at least 2 hours after micturition, using a calcium-alginate swab on a nonwooden stick inserted at least 1 cm in depth to help prevent false-negative findings. Chlamydia ligase chain reaction is 90-95% sensitive and nearly 100% specific. Obtain samples on swabs at least 2 hours after micturition, using a calcium-alginate swab on a nonwooden stick inserted at least 1 cm in depth to help prevent false-negative results.
  • DNA-based tests, unlike culture, do not allow for antibiotic susceptibility testing, but this is not necessary for most patients.
• Potassium hydroxide preparation: Fungal organisms, if present, are noted.
• Wet preparation: Secretions reveal the movement of trichomonal organisms, if present.
• Patients with urethritis should be counseled about the risk of more serious STDs. They should be offered syphilis serology (Venereal Disease Research Laboratory test or Rapid Plasma Reagin test) and HIV serology.
• Women who have had unprotected intercourse should be offered pregnancy testing.
• Patients with Reiter syndrome are diagnosed based on the presence of nongonococcal urethritis and clinical findings of uveitis and reactive 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 a retrograde urethrogram, are not necessary for patients with urethritis, except in cases of trauma or possible foreign body insertion.

Procedures

• 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 cystocope can allow passage of a guidewire, over which the Council 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 tube 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).
• Filiforms and followers: Filiforms and followers can also be used by experienced urologists but are being 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 tube placement: With more severe urethral trauma preventing 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

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Symptoms spontaneously resolve over time in all patients with urethritis, regardless of treatment. Administer antibiotics to prevent morbidity and to reduce transmission to others. Treating sexual contacts also prevents reinfection of the index patient.

Antibiotic therapy should cover both GC and NGU. If concomitant treatment for NGU is not given, the occurrence rate of postgonococcal urethritis is approximately 50%. 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.

Activity

• Instruct the patient to refrain from intercourse until all partners are treated.
• Educate the patient about always using barrier devices when engaging in intercourse with multiple partners.
• Inform patients that infections can spread by orogenital or genitoanal intercourse, even in the absence of penovaginal intercourse.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Administer antibiotics to patients with positive Gram stain or culture results and to all sexual partners of those patients, regardless of symptoms. Also treat 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 (eg, prostitutes, persons who abuse drugs, homeless persons). The latter group may best be served with single-dose therapies (see below).

Drug Category: Antibiotics

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. The antimicrobial options in the treatment of urethritis include parenteral ceftriaxone, oral azithromycin, oral ofloxacin, oral ciprofloxacin, oral cefixime, oral doxycycline, or parenteral spectinomycin. Azithromycin and doxycycline have been proven equally efficacious in treating C trachomatis. Ofloxacin and azithromycin are effective for NGU, whereas ciprofloxacin is ineffective against chlamydial infection. Combinations of probenecid with penicillin, amoxicillin, or ampicillin are no longer used because of resistance. Conversely, the macrolides, including erythromycin, and tetracyclines all have similar effectiveness in patients with NGU. The incidence of quinolone-resistant N gonorrhea is high in Asian and Pacific nations and is rising in the West Coast of the United States. Obtaining a recent travel history may help direct therapy.

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 cefixime, ceftriaxone, ciprofloxacin, ofloxacin, or levofloxacin for N 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.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Outpatient Care

• Obtain follow-up cultures to ensure eradication of infection only if the patient remains symptomatic.
• If symptoms continue following adequate treatment, then the disease is most likely 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 prolonged (14-28 d) therapy with erythromycin. Consider also quinolone resistance in GU, based on local epidemiologic data.
• 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.

Deterrence/Prevention

• Educate at-risk patients on how to prevent disease recurrence.
• Educate patients on risks of other sexually-transmitted infections, including HIV.
• Try to find asymptomatic patients and symptomatic patients who are unlikely to seek treatment.
• Early diagnosis and treatment of infected individuals is essential.
• Evaluate and treat sexual partners of known infected persons.

Complications

• Complications, such as stricture, stenosis, or abscess formation, are quite rare. Concomitant epididymitis or prostatitis is not uncommon.

Prognosis

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

Patient Education

• Instruct patients to avoid the following high-risk behaviors, which are associated with STDs:
• • Intercourse at a young age, with rare exception, is associated with multiple sex partners and unprotected intercourse.
  • Intercourse with multiple partners
  • Drug abuse
  • Unprotected sex
  • Intercourse with partners known to have infections
• Instruct patients to use barrier devices with all partners at all times.
• For excellent patient education resources, visit eMedicine's Kidneys and Urinary System Center and Pregnancy and Reproduction Center. Also, see eMedicine's patient education articles Urinary Tract Infections, Birth Control Spermicides, Birth Control FAQs, and Birth Control Overview.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to detect or treat co-infections
• Failure to identify and treat partners
• Failure to screen for other STDs

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Anagrius C, Lore B, Jensen JS. Mycoplasma genitalium: prevalence, clinical significance, and transmission. Sex Transm Infect. Dec 2005;81(6):458-62. [Medline].
• Berger RE. Sexually Transmitted Diseases: The Classic Diseases. In: Walsh PC, Retik AB, Vaughan ED, eds. Campbell's Urology. 7th ed. Philadelphia, Pa: WB Saunders; 1998:. 663-70.
• Centers for Disease Control and Prevention. CDC Division of AIDS, STD, and TB. Gonococcal Isolation Surveillance Project (GISP) Annual Report - 1998. Atlanta, Ga: Centers for Disease Control and Prevention; 1998. [Full Text].
• Chorba T, Tao G, Irwin K. Sexually Transmitted Diseases. In: Litwin MS, Saigal CS, eds. Urologic Diseases in America. 2004;233-79. [Full Text].
• Frenkl T, Potts J. Sexually Transmitted Infections: Part II - Associated Vaginitides and Urethritides. AUA Update Series. 2006;25:17-9.
• Isselbacher HK, Braunwald E, Wilson JD et al, eds. Harrison's Principles of Internal Medicine. 13th ed. New York, NY: McGraw-Hill; 1994.
• Kataria RK, Brent LH. Spondyloarthropathies. Am Fam Physician. Jun 15 2004;69(12):2853-60. [Medline].
• Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 5th ed. New York, NY: Churchill Livingstone; 1998.
• National Institute of Allergy and Infectious Diseases. Fact Sheet. STD Statistics. Bethesda, Md: National Institutes of Health; December 1998. [Full Text].
• Workowski KA, Levine WC. Selected topics from the Centers for Disease Control and Prevention Sexually Transmitted Diseases Treatment Guidelines 2002. HIV Clin Trials. Sep-Oct 2002;3(5):421-33. [Medline]. [Full Text].

Article Last Updated: May 3, 2006