Chapter 2

Chapter 2 

URETHRITIS IN MALES 

ETIOLOGY 

Urethritis is the most frequent STD syndrome seen in men. Customarily, clinicians categorize 

urethritis into gonococcal and nongonococcal etiologies. The relative frequency of nongonococcal 

urethritis (NGU) and gonococcal urethritis varies by population studied, but overall, more cases of 

NGU than gonococcal urethritis are now being seen in the United States. Up to one-fourth of heterosexual 

men with gonorrhea also have simultaneous Chlamydia trachomatis (CT) infections. 

C. trachomatis causes 20 to 40% of cases of NGU, and some studies indicate that Mycoplasma 

genitalium and Ureaplasma urealyticum may cause an additional 10 to 20%. The remaining cases 

probably result from sexually transmitted pathogens, but their precise etiology remains unclear. Occasionally, 

urethritis results from infection with Trichomonas vaginalis, adenovirus or herpes simplex 

virus. 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 with trichomonal vaginitis. 

INCUBATlON PERIOD 

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 

Nongonococcal urethritis (mucoid 

discharge) [1] 

Both gonococcal and nongonococcal urethritis typically cause urethral 

discharge, dysuria, or urethral itching. Three-quarters of men with gonococcal 

urethritis have purulent urethral discharge, and three-quarters of men 

with chlamydial or culture-negative NGU have clear or mucoid discharge. A 

Gonococcal urethritis 

(purulent discharge) [2] 

significant proportion of men with urethral chlamydial infections are asymptomatic; conversely, most 

urethral gonococcal infections are symptomatic. 

DIAGNOSIS 

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). It should be emphasized that 

clinical features alone do not reliably differentiate between gonococcal and nongonococcal urethritis. For 

8 

Chapter 2 - Urethritis in males

this reason, diagnosis and 

treatment should be based 

on the results of a urethral 

Gram stain and appropriate 

cultures or tests. 

Document 

Urethritis 

by the presence of at least 

two of the following three 

features: 

1. Symptoms: history 

of urethral 

discharge and/or 

dysuria 

2. Examination: presence 

of purulent, 

mucopurulent, or 

mucoid urethral 

discharge 

3. Laboratory: (any 

one of following is 

sufficient) 

Intacellular Gram-negative diplococci 

(GNDC) in urethral Gram stain [3] 

Lesion of disseminated gonococcal 

infection [5] 

• urethral Gram-stained smear showing ≥5 PMNs/1000X field in areas of maximal cellular 

concentration 

• urinalysis showing ≥10 PMNs/400X field in centrifuged sediment 

• positive urine leukocyte esterase test 

Patients with symptoms of urethritis, but without a visible discharge on exam or laboratory evidence 

of urethritis, should be reexamined within 7 days when they have not urinated for 4 to 8 hours. 

If only one diagnostic criterion is met on reexamination, obtain the first 5 to 10 ml of voided urine, 

centrifuge, and examine the sediment microscopically: ≥10 PMNs/400X field confirms urethritis. 

A urethral Gram-stained smear showing ≥5 PMNs/l000X field is suggestive of urethritis, even in 

the absence of other criteria. 

Exclude Gonorrhea 

1. Gram-stained smear of urethral exudate 

• negative for intracellular Gram-negative diplococci (IGND) 

2. Confirmed by negative culture for N. gonorrhoeae (GC) 

Urethral Gram stain with >5 PMNs 

per high power field (nongonococcal 

urethritis) [4] 

Normal urethral cells on Gram stain [6] 

Test for Chlamydia 

Obtain urethral specimen for C. trachomatis (CT) antigen-detection or DNA test, culture, or NAAT 

(LCR, PCR). 

9 


Sexually active man with history of urethral 

discharge or dysuria or sexual contact with 

an infected partner 

Abnormal urethral discharge on examination 

Yes 

No 

Gram-stained smear of 

urethral exudate or 

endourethral smear 

Gram-stained 

endourethral smear* 

No GND; ≥5 PMNs 

/ 1000X field 

Extracellular GND 

or intracellular GND 

with atypical 

morphology 

PMNs with 

intracellular GND 

No GND;

TREATMENT 

For a more detailed discussion of these regimens and other treatment considerations, please refer 

to the CDC 

STD Treatment Guidelines 

at http://www.cdc.gov/std/treatment/. 

Gonococcal Urethritis 

Uncomplicated anogenital gonorrhea 

Any of the following: 

• Cefixime 400 mg PO (single dose) 

• Ciprofloxacin 500 mg PO (single dose) 

• Ofloxacin 400 mg PO (single dose) 

• Levofloxacin 250 mg PO (single dose) 

• Ceftriaxone 125 mg IM (single dose) and doxycycline 100 mg bid for 7 days 

Note: 1) Doxycycline is also provided with any of the above treatments for empirical treatment 

of possible coexisting C. trachomatis infection. Alternatively, azithromycin 1 gm PO 

single dose can be used instead of doxycycline for treatment of possible co-existing 

chlamydial infection. 

2) Avoid flouroquinones if gonococcal infection was acquired in Hawaii or southeast Asia, due 

to higher rates of quinolone resistance in GC or if treating MSM infected with gonorrhea. 

3) Cefixime is currently not available in pill form, but is expected to be back on the market 

sometime in late 2004. In the interim, Cefpodoxime 400 mg PO (single dose) is being recommended 

and is under formal study. The liquid formulation of Cefixime is still available 

though not feasible or available in most clinics. 

Nongonococcal Urethritis 

Recommended regimens 

Either of the following: 

• Azithromycin 1 g orally in a single dose, 

• Doxycycline 100 mg orally twice a day for 7 days 

Alternative regimens 

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, 

• Ofloxacin 300 mg twice a day for 7 days or Levofloxacin 500 mg once daily for 7 days 

Immediate treatment failure 

(persistent urethritis while on therapy or recrudescence immediately after completion of treatment) 

1. Confirm urethritis by examination and laboratory. 

2. Obtain urethral wet prep and culture for trichomonas. 

3. Pending results of trichomonas culture: 

• Treat with erythromycin if doxycycline was used initially 

- Erythromycin stearate or base 500 mg qid for 7 days 

4. Treat with metronidazole 2 gm PO single dose (microscopy of first-void urine or urethral 

swabs shows trichomonads or if trichomonas culture is positive, or empirically if culture is 

unavailable) 

• Treat with doxycycline if erythromycin was used initially 

- Doxycycline 100 mg bid for 7 days 

11 


Recurrence of urethritis 

(within 6 weeks, following apparent resolution) 

1. Evaluate to confirm the diagnosis of urethritis. 

2. Confirm that the treatment was followed and whether or not the patient had sexual activity 

before he or his partner were fully treated. If the patient has been noncompliant or has been 

exposed to an untreated partner, retreat with the original regimen. 

3. Retreat with Metronidazole 2 g orally in a single dose, plus 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. 

FOLLOW-UP 

Initial or isolated episode 

Patients with gonococcal urethritis 

A test-of-cure is recommended only for patients with a known resistant strain of GC or for 

those with persistent symptoms. 

Men with NGU 

Request a return after 7 to l4 days only if symptoms persist or recur. 

Persistent or recurrent NGU 

Request that patients return prn 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 (see Appendix 

B). 

MANAGEMENT OF SEX PARTNERS 

All contacts within the previous 4 weeks, 

and any other contacts suggested by the epidemiologic history: 

1. Perform routine STD examination. 

2. Regular partners and source contacts 

• of gonorrhea: 

Treat with cefixime 400 mg PO (or other single dose regimen listed above) and provide 

doxycycline for possible coexisting C. trachomatis infection. 

• of chlamydia urethritis or CT-NGU: 

Treat with doxycycline, ofloxacin or azithromycin. 

When practical, use the same regimen used for the patient, unless contraindicated because 

of pregnancy or drug intolerance. 

3. Casual contacts: 

Individualize treatment, depending on the clinical examination, epidemiologic setting (for 

example, suspected source vs. spread contact), and results of gonorrhea and chlamydia tests. 

Do not dispense antibiotics or prescriptions for contacts who are not examined, except in special 

circumstances. 

Contacts of men with recurrent NGU 

The need and value of treatment are unknown. Individualize the approach on the basis of available 

clinical, epidemiological, and microbiological data. 

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SEQUELAE 

With the advent of antibiotics, complications as a result of gonococcal urethritis, such as locally 

invasive infection, urethral strictures, or disseminated gonococcal infection 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. Reiterʼs syndrome may result from untreated 

chlamydial urethritis in genetically predisposed individuals. The 

psychological impact of persistent urethritis or frequent recurrences 

can be great. 

LABORATORY SCREENING FOR URETHRITIS IN 

ASYMPTOMATIC MEN 

A urethral Gram stain and cultures for chlamydia and gonorrhea 

should be obtained from heterosexual men who are seen in 

high-risk settings such as an STD clinic and who have no history 

of urethral symptoms or signs and no history of contact with an 

infected partner. An example of columnar epithelial cells obtained 

from an endourethral swab from an asymptomatic man is shown to 

the right; the presence of columnar epithelial cells indicates that the 

swab specimen has been obtained adequately to test for C. trachomatis. 

Some of these men will have asymptomatic gonorrhea or 

NGU as evidenced by persistent urethral leukocytosis, pyuria (as 

measured by urine microscopy or LE test), and/or a positive test 

for chlamydia or gonorrhea. 

Lesion of disseminated gonococcal 

infection [5] 

Normal urethral cells on Gram 

stain [6] 

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Chapter 2

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