Urethritis is defined as infection-induced inflammation of the urethra. The term is typically reserved to describe urethral inflammation caused by a sexually transmitted disease (STD), and the condition is normally categorized as either gonococcal urethritis (GU) or nongonococcal urethritis (NGU).
Many patients with urethritis, including approximately 25% of those with NGU, are asymptomatic and present to a clinician following partner screening.[1] Up to 75% of women with Chlamydia trachomatis infection are asymptomatic.
Signs and symptoms in patients with urethritis may include the following:
See Presentation for more detail.
Most patients with urethritis do not appear ill and do not present with signs of sepsis. The primary focus of the examination is on the genitalia.
Examination in male patients with urethritis includes the following:
Examine female patients in the lithotomy position. Include the following evaluation:
Testing
Urethritis can be diagnosed based on the presence of one or more of the following:
All patients with urethritis should be tested for Neisseria gonorrhoeae and C trachomatis. Laboratory studies may include the following:
Imaging studies
Imaging studies, specifically retrograde urethrography, are unnecessary in patients with urethritis, except in cases of trauma or possible foreign body insertion.
Procedures
Patients with urethritis may undergo the following procedures:
See Workup for more detail.
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:
Antibiotics used in the treatment of urethritis include the following:
See Treatment and Medication for more detail.
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 gonococcal urethritis (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).
Haemophilus species are an increasing cause of NGU, particularly in men who have unprotected oral sex with men.[2, 3] Rare infectious causes of urethritis include lymphogranuloma venereum, herpes simplex virus types 1 and 2, adenovirus, syphilis, mycobacterial infection, Corynebacterium,[4] 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, none of the known viral or bacterial causes are found.in up to 35% of NGU cases.[5]
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 the following:
Urethritis occurs in 4 million Americans each year. The incidence of gonococcal urethritis 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 gonococcal urethritis declined steadily from 2000 to 2009, but then began an intermittent rise, and the incidence of NGU is increasing.[6] NGU incidence is highest in the summer months.
Worldwide, approximately 62 million new cases of gonococcal urethritis and 89 million new cases of NGU are reported each year.
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 antichlamydial 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.
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 underrecognized in women. Up to 75% of females with the condition can be asymptomatic or may instead present with cystitis, vaginitis, or cervicitis.[7] Homosexual males 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.
All patients with uncomplicated urethritis spontaneously recover with or without treatment.
Obtaining a careful patient history often helps differentiate between a sexuallly transmitted disease (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, including the chain of partners that may be linked to the patient (eg, partners of partners and so on).
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 either 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
Except in 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 sexual 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 are at an increased risk of contracting another STD. Concurrent STDs may also occur. A high level of suspicion for other 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.
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:
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]).
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.
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, as 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.
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 findings that indicate systemic disease are as follows:
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:
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.
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.
Urethritis can be diagnosed based on the presence of one or more of the following[8] :
All patients with urethritis should be tested for Neisseria gonorrhoeae and Chlamydia trachomatis.
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.
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 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.
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.
Polymerase chain reaction assays are available for gonococcal urethritis and Chlamydia infection. 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 unnecessary in most patients.
The following additional tests may be considered:
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, 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 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 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.
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.
Symptoms of urethritis spontaneously resolve over time, regardless of treatment. Administer antibiotics to prevent morbidity and to reduce disease transmission to others. Treating sexual contacts also prevents reinfection of the index patient.
Antibiotic therapy should cover both gonococcal urethritis and nongonococcal urethritis (NGU). If concomitant treatment for NGU is not provided, the risk 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.
For treatment of NGU, the Centers for Disease Control and Prevention (CDC) currently recommends azithromycin, 1 g orally in a single dose, or doxycycline, 100 mg orally twice a day for 7 days.[8, 9] Alternative regimens include any of the following:
For uncomplicated gonococcal urethritis, the CDC recommends single doses of ceftriaxone, 250 mg IM, and azithromycin, 1 g orally; preferably, the two antibiotics should be administered simultaneously and under direct observation. If ceftriaxone is unavailable, cefixime, 400 mg orally in a single dose, can be substituted.[8]
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.[11]
Because of widespread high levels of resistance, the WHO guidelines do not recommend quinolones 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[11] :
Patients with persistent symptoms should be reevaluated. In patients with a repeat diagnosis of NGU after treatment with doxycycline, the most common organism is Mycoplasma genitalium. Men in whom a treatment regimen of doxycycline fails should be treated with azithromycin 1 g orally in a single dose; if azithromycin fails, recommended treatment is with moxifloxacin, 400 mg once daily for 7 days, as studies have shown this dosing is highly effective against M genitalium.[9]
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.[9]
See also Urethritis Empiric Therapy and Urethritis Organism-Specific Therapy.
See the list below:
Consider urology consultation in patients with persistent or recurrent NGU after presumptive treatment for gonococcal urethritis, NGU, and M genitalium or T vaginalis [9]
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).
Clinical Context: In 2-g dose, treats both gonococcal urethritis and NGU. Treatment of choice and is well tolerated by most patients. Eight large tabs are required, and liquid is also available.
Clinical Context: Used for gonococcal urethritis only. Third-generation cephalosporin with broad-spectrum gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. Arrests bacterial growth by binding to 1 or more penicillin-binding proteins.
Clinical Context: Treats gonococcal urethritis only. By binding to 1 or more of the penicillin-binding proteins, arrests bacterial cell wall synthesis and inhibits bacterial growth.
Clinical Context: Treats gonococcal urethritis only. Fluoroquinolone with activity against pseudomonads, streptococci, MRSA, Staphylococcus epidermidis, and most gram-negative organisms but offers no activity against anaerobes. Inhibits bacterial DNA synthesis and, consequently, growth.
Clinical Context: Treats gonococcal urethritis only. Penetrates prostate well and is effective against N gonorrhea and C trachomatis. A derivative of pyridine carboxylic acid with broad-spectrum bactericidal effect.
Clinical Context: Treats NGU only. Inhibits protein synthesis and, thus, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.[12]
The antimicrobial options in the treatment of urethritis include parenteral ceftriaxone, oral azithromycin, oral ofloxacin, oral ciprofloxacin, oral cefixime, oral doxycycline, and parenteral spectinomycin. Azithromycin and doxycycline have been proven equally efficacious in treating C trachomatis infections. Ofloxacin and azithromycin are effective for nongonococcal urethritis (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 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 gonococcal urethritis 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.
See the list below:
See the list below:
Complications, such as stricture, stenosis, or abscess formation, are quite rare. Concomitant epididymitis or prostatitis is not uncommon.
PID and tubo-ovarian abscess are known complications of urethritis in females that may predispose to infertility. In addition, 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.[13, 14, 15]
All patients with uncomplicated urethritis spontaneously recover with or without treatment.
Instruct patients to avoid the following high-risk behaviors are associated with STDs:
Instruct patients to use barrier devices with all partners at all times.
For patient education information, see Urinary Tract Infections, Birth Control Spermicides, Birth Control Methods, and Birth Control Overview.