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Chapter 2: Urethritis in Males

ETIOLOGY

Urethritis is the most frequent STD syndrome seen in men. It is characterized by urethral inflammation and has traditionally been classified as gonococcal or nongonococcal urethritis (NGU). Despite the fact that N. gonorrhoeae encompass the more clinically important infectious causes of male urethritis, C. trachomatis is the causative agent in 15-40% and Mycoplasma genitalium (M. genitalium) appears to account for 15-25% of NGU cases in the U.S. Other potential pathogens in urethritis include T. vaginalis, HSV and adenovirus. Support for other Mycoplasma and Ureaplasma species being causative pathogens in urethritis remains inconsistent. Most patients with urethritis due to genital herpes infection will have obvious herpetic penile lesions, and many with urethritis due to T. vaginalis will have sex partners who also have this infection. Less commonly, some enteric bacteria may be causative agents of urethritis in men who are insertive partners in anal intercourse.

INCUBATlON PERIOD

Image 2-1. Gonococcal urethritis
Image 1.
Gonococcal urethritis
Image 2-2. Nongonococcal Urethritis (mucoid discharge)
Image 2.
Nongonococcal urethritis

Gonorrhea usually develops 2 to 6 days after exposure to Neisseria gon­orrhoeae (GC), whereas NGU gener­ally develops between 1 and 5 weeks after infection, with a peak around 2 weeks.

CLINICAL MANIFESTATIONS

Urethritis is characterized by either clear, mucopurulent or purulent urethral discharge, dysuria, or urethral pruritus.  Classically, men with gonococcal urethritis more likely have purulent discharge [Image 1] and those with non-gonococcal urethritis tend to have clear or mucoid discharge [Image 2].  A significant proportion of men with chlamydial urethritis are asymptomatic; conversely, most gonococcal urethral infections are symptomatic.

DIAGNOSIS

All men with suspected urethritis should be tested for gonorrhea and chlamydia. The availability of sensitive and specific testing methods such as nucleic acid amplification tests (NAAT) promote efficient diagnosis, treatment and expedited opportunity to test and treat sex partners.

The diagnostic approach to men with urethritis begins by distinguishing those patients who have urethral discharge on examination from those who do not (see Figure 2-1). Clinical features alone do not reliably differentiate between gonococcal and nongonococcal urethritis. For this reason, diagnosis and treatment should be based on the results of appropriate tests or culture of urine or urethral specimens (see images 4 and 5 below). 

Urethritis is documented on the basis of any of the following signs or laboratory tests (CDC 2010 STD Treatment Guidelines):

image 3. Intracellular Gram-negative diplococci
Image 3.
Intracellular
Gram-negative diplococci
Image 2-4. Urethral Gram stain
Image 4.
Urethral Gram stain
Image 5. Normal urethral cells
Image 5
Normal urethral cells

  • Mucopurulent or purulent discharge on urethral examination.
  • When available, Gram stain of urethral secretions demonstrating ≥5 WBC per oil immersion field.  The Gram stain is the most sensitive and specific test for documenting urethritis and evaluating for the presence of gram-negative diplococci, consistent with gonococcal infection (see images 3 and 4).
  • Positive leukocyte esterase test on first-void urine of microscopic examination of first-void urine sediment demonstrating ≥10 WBC per high-power field.

If none of these criteria are fulfilled, the practitioner should proceed with testing for N. gonorrhoeae and C. trachomatis using NAAT. Additionally, empiric therapy targeted against both these pathogens would be a reasonable option in high risk individuals who are not likely to return for follow-up evaluation.

Figure 2-1 Management of a male with possible urethritis.

TREATMENT

For a more detailed discussion of regimens and treatment considerations, please refer to the 2010 CDC STD Treatment Guidelines at www.cdc.gov/std/treatment.

Gonococcal Urethritis

Effective treatment of gonorrhea is complicated by its ability to develop antimicrobial resistance. Based on data from the Gonococcal Isolate Surveillance Project (GISP), the CDC updated its treatment recommendations from the 2010 CDC STD Treatment Guidelines. As of August 2012, CDC no longer recommends cefixime at any dose as a first-line regiment for treatment of gonococcal infections. Instead, ceftriaxone as a single intramuscular injection of 250 mg in combination with a second antimicrobial (azithromycin as a single 1 g oral dose or doxycycline 100 mg orally twice daily for 7 days) is recommended. Moreover, CDC advises a test of cure at one week for any person who undergoes treatment with a non-ceftriaxone regimen.

When ceftriaxone cannot be used for treatment, two alternative options are available: cefixime 400 mg orally plus either azithromycin 1 g orally or doxycycline 100 mg twice daily orally for 7 days, or azithromycin 2 g orally in a single dose if ceftriaxone cannot be given because of severe allergy. Practitioners are encouraged to obtain gonococcal cultures particularly when prescribing non-ceftriaxone treatment regimens for the purpose of following up on antimicrobial susceptibilities. 

Recommended Regimens for Gonococcal Urethritis

Ceftriaxone 250 mg in a single intramuscular dose

PLUS

Azithromycin 1 g orally in a single dose

OR

Doxycycline 100 mg orally twice daily for 7 days*

Alternative Regimens

If ceftriaxone is not available:

Cefixime 400 mg in a single oral dose

PLUS

Azithromycin 1 g orally in a single dose

OR

Doxycycline 100 mg orally twice daily for 7 days*

PLUS

Test-of-cure in 1 week

If the patient has severe cephalosporin allergy:

Azithromycin 2 g in a single oral dose

PLUS

Test-of-cure in 1 week

* Because of the high prevalence of tetracycline resistance among Gonococcal Isolate Surveillance Project isolates, particularly those with elevated minimum inhibitory concentrations to cefixime, the use of azithromycin as the second antimicrobial is preferred.

Nongonococcal Urethritis

Recommended Regimens

Azithromycin 1 g orally in a single dose

OR

Doxycycline 100 mg orally twice a day for 7 days

Alternative Regimens

Erythromycin base 500 mg orally four times a day for 7 days

OR

Erythromycin ethylsuccinate 800 mg orally four times a day for 7 days

OR

Levofloxacin 500 mg orally once daily for 7 days

OR

Ofloxacin 300 mg orally twice a day for 7 days

Men treated for urethritis should be advised to abstain from sexual activity for 7 days after a single-dose therapy or until completion of a 7-day regimen, assuming resolution of symptoms.  Individuals who are diagnosed with either gonorrhea or chlamydia should undergo additional testing for other STDs, including syphilis and HIV, and female partners should receive expedited partner therapy (EPT) if not evaluated directly. While the CDC does not explicity recommend EPT for men who have sex with men given that in-person evaluation would allow the opportunity to evaluate for undiagnosed HIV infection or other STD, including syphilis, the main goal should be to ensure the treatment of affected partners; practitioners should use their best judgment in this regard.

Recurrent and Persistent Urethritis

Individuals should return for care if symptoms persist beyond 7 days after treatment.  Providers should pursue culture and antimicrobial susceptibility profiles for gonococcal urethritis, as discussed in the prior section. Also, providers should consider the possibility of prostatitis in the setting of individuals who experience ongoing penile/perineal or pelvic pain, dysuria, pain with ejaculation or premature ejaculation that lasts for a minimum of three months.  For those individuals treated with recommended regimens for documented gonorrhea or chlamydia, a test of cure is not warranted. However, due to high rates of re-infection from untreated sex partners, repeat testing for these STDs is recommended 3 months after treatment. 

There is no evidence to support extending the course of therapy for men with persistent symptoms who receive recommended therapy, assuming they have not been re-exposed to an untreated sex partner.  Doxycycline-resistant strains of M. genitalium or U. urealyticum have been detected, leading some experts to suggest a possible role for azithromycin (single dose), or moxifloxacin (400 mg orally once daily for 7 days) for men who do not respond to either doxycycline or azithromycin, respectively (Bradshaw, Chen et al. 2008). 

T. vaginalis can cause urethritis, particularly in heterosexual men.  If this infection is suspected, evaluation should consist of urethral swab, first void urine or semen for culture of the organism or NAAT assay.

Treatment of recurrent or persistent urethritis is recommended as follows:

Recommended Regimens

Metronidazole 2 g orally in a single dose

OR

Tinidazole 2 g orally in a single dose

PLUS

Azithromycin 1 g orally in a single dose (if not used for initial episode)

FOLLOW-UP

Initial or isolated episode

Men with gonorrhea

Routine re-evaluation is not generally recommended when patients receive first-line treatment. A test-of-cure is recommended for patients:

  • with persistent symptoms
  • that are treated with a non-ceftriaxone regimen
  • at risk of re-infection
  • suspected of non-adherence to treatment

Men should be re-screened for gonorrhea (and chlamydia) 3 months after initial infection.

Men with NGU

Routine re-evaluation is not recommended. Re-evaluate after 7 to 14 days only if symptoms persist or recur.

Persistent or recurrent NGU

Request that patients return as needed for persistent or recurrent symptoms.  Consider referral to a urologist or other specialist.

Confirmed cases of gonorrhea and chlamydia should be reported to the state/local health department.

MANAGEMENT OF SEX PARTNERS

All contacts within the past 60 days

All sex partners within this timeframe should be offered appropriate evaluation, testing and treatment if they have had sexual contact with the patient during the 60 days of STD diagnosis. Patient-delivered partner therapy (PDPT), a form of expedited partner therapy (EPT), entails delivery of either a prescription or the medication itself by the primary patient to partner, and is encouraged in many settings among heterosexuals (see www.cdc.gov/std/ept for further details). As noted above, the approach of EPT is not , routinely recommended among men who have sex with men because of a high risk for coexisting infections, especially undiagnosed HIV among partners, but should be considered in the armamentarium of options for managing partners if no other options are available.

Patients are encouraged to abstain from sexual activity until 7 days after a single-dose regimen or after completion of a multiple-dose regimen.

SEQUELAE

With the advent of antibiotics, complications as a result of gonococcal urethritis, such as locally invasive infection, urethral strictures, or disseminated gonococcal infection [Image 6] are now rare.  NGU is generally a self-limited disease and, even without therapy, clinical consequences are minimal.  Epididymitis can develop in up to 2% of cases, and conjunctivitis occasionally occurs.  Reactive arthritis may result from untreated chlamydial urethritis in genetically predisposed individuals.

Image 2-6. Disseminated gonococcal infection
Image 6.
Disseminated gonococcal infection

 

 


Reference:
Bradshaw, C. S., M. Y. Chen, et al. (2008). Persistence of Mycoplasma genitalium following azithromycin therapy. PLoS One 3(11): e3618.

CDC. Update to CDC's sexually transmitted diseases treatment guidelines, 2010: oral cephalosporins no longer a recommended treatment for gonococcal infections. MMWR 2012:61(31); 590-594

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