Section 4-7: Canadian Guidelines on Sexually Transmitted Infections – Management and treatment of specific syndromes – Urethritis

The 2016 Updates Summary, the 2014 Supplementary Statement and the Laboratory Diagnosis of Sexually Transmitted Infections chapter, revised in 2016, contain important information pertaining to this chapter. They should be used in conjunction with this 2010 chapter to ensure that you are implementing the most current recommendations in your practice.

Section 4 - Management and Treatment of Specific Syndromes

Urethritis

Definition

  • Clinical syndrome:
    • Inflammation of the urethra, with or without urethral discharge.
    • Discharge, if present, can be mucoid, mucopurulent or purulent.
    • May also be manifested by dysuria, urethral pruritus or meatal erythema.
  • Microscopic definition: presence of ≥5 polymorphonuclear leukocytes (PMNs) per oil immersion field (x1000) in five non-adjacent, randomly selected fields on a smear.Footnote 1
  • Non-gonococcal urethritis (NGU) refers to urethritis not caused by N. gonorrhoeae.

EtiologyFootnote 2

Epidemiology

  • Limited data are available on the incidence or prevalence of urethritis.

Natural history

  • Symptoms of gonococcal urethritis develop 2 to 6 days after acquisition.
  • Symptoms of NGU develop 1 to 5 weeks after acquisition (usually at 2–3 weeks).
  • Up to 25% of infections, especially NGU, can be asymptomatic.Footnote 10

Prevention and Control

  • Use clinical evaluation as an opportunity to review safer sexual practices, explore barriers to adopting these practices and problem-solve to overcome such barriers in the future.
  • Advise on consistent condom use.
  • Advise patient to abstain from unprotected intercourse until 7 days after initiating treatment.

Manifestations

  • Urethral discharge.
  • Dysuria.
  • Urethral itching or meatal erythema.
  • Often asymptomatic.
  • Although urinary frequency, hematuria and urgency can, on rare occasions, occur with urethritis, the presence of any of these symptoms requires more extensive evaluation.

Diagnosis

Specimen collection
  • Discharge: obtain sample by having patient milk penis three to four times from base to glans.Footnote 11
  • Endourethral swab: pass swab 2 cm into the urethra, rotate and remove for Gram stain and testing.
  • Urine sample: obtain first 10–20 ml of first-catch urine, any time of day, but preferably after having not voided for at least 2 hours.Footnote 12
Laboratory diagnosis
  • Testing for both gonorrhea and chlamydia is recommended (See Chlamydial Infections and Gonococcal Infections chapters for more information on testing).
  • Obtain the following:
    • Gram stain of discharge or endourethral specimen for PMNs and Gram-negative diplococci (if available).
    If nucleic acid amplification tests (NAAT) are available:
    • NAAT of urine for C. trachomatisFootnote 13,Footnote 14 and culture of endourethral swab for N. gonorrhoeae.
    If NAAT is unavailable:
    • Direct fluorescent antibody (DFA), enzyme immunoassay (EIA), or culture for C. trachomatisFootnote 14 and culture of endourethral swab for N. gonorrhoeae.
  • Although NAAT testing for gonorrhea may be considered in cases where transport and storage conditions are not conducive to maintaining the viability of N. gonorrhoeae or obtaining a swab is not possible, culture is the preferred method, because it allows for antimicrobial susceptibility testing.

Caution

  • Presence of the following symptoms suggest an alternative diagnosis:
    • Hematuria.
    • Fever, chills.
    • Frequency, nocturia, urgency.
    • Perineal pain, scrotal masses.
    • Difficulties initiating and maintaining stream.
    • Lymphadenopathy

Management and Treatment (see Figure 1)

Gonococcal urethritis

Cefixime 400 mg PO in a single dose PLUS EITHER doxycycline 100 mg PO bid for 7 daysFootnote 15 [A-l] OR azithromycin 1 g PO in a single dose if poor compliance is expected [A-l].

Non-gonococcalurethritis

Doxycycline 100 mg PO bid for 7 daysFootnote 16Footnote 18 [A-l] OR azithromycin 1 g PO in a single dose if poor compliance is expected [A-l].

  • Alternative regimens are available for gonococcal infections/chlamydial infections (see Gonococcal Infections and Chlamydial Infections chapters).
  • Single-dose regimens offer improved compliance and are especially useful in certain populations such as street youth, but they are also the most expensive.
  • Resolution of symptoms can take up to 7 days after therapy has been completed.
  • Patients and contacts should abstain from unprotected intercourse until treatment of both partners is complete (i.e. after completion of multiple dose treatment or for 7 days after single dose therapy).
  • Asymptomatic infections in men are common and should be treated.

Consideration for Other STIs

  • Obtain serology for syphilis.
  • Review immunization status for hepatitis B; offer vaccination if the patient is not protected and testing if the patient is at high risk.
  • Offer HIV testing and counselling.
  • In men who have sex with men, consider hepatitis A vaccine.

Reporting and Partner Notification

  • Urethritis caused by certain agents (e.g., C. trachomatis, N. gonorrhoeae) is a notifiable communicable disease for provinces and territories. All conditions and diseases that are notifiable should be reported to public health departments in accordance with local regulations and laws.
  • Sexual partners should be traced 60 days prior to symptom onset or date of specimen collection (if asymptomatic).
    • The length of time for the trace-back period should be extended:
      1. to include additional time up to the date of treatment
      2. if the index case states that there were no partners during the recommended trace-back period, then the last partner should be notified
      3. if all partners traced (according to recommended trace-back period) test negative, then the partner prior to the trace-back period should be notified.
  • Partners should be tested and treatment considered,(see Figure 1 in this chapter).
  • Where possible, encourage the use of public health authorities or treating physician to conduct contact tracing on partners and increase the number of partners contacted.Footnote 19
  • All sexual partners of the index case from 60 days prior to symptom onset or date of diagnosis (if asymptomatic) should be tested and empirically treated regardless of clinical findings and without waiting for test results. If there was no partner during this period, then the last partner should be tested and treated.

Follow-up

  • If treatment is taken and symptoms resolve, test of cure is not routinely recommended.
  • If symptoms persist or recur after completed therapy (1 week after initiation of therapy), the patient should be re-evaluated.
  • Symptoms alone are not sufficient for retreatment in the absence of laboratory findings or clinical signs.
  • If a test of cure is indicated and NAAT is being used for follow-up testing, testing should not be conducted until 3 weeks after treatment to avoid a false positive.

Special Considerations

Recurrent or persistent urethritis
  • Often a difficult problem.
  • Reconfirming the presence of urethritis using smear and Gram stain is essential.
  • Critical to differentiate urethritis from functional complaints.
  • Important to inform patient at the start of care for recurrent urethritis that it can be a difficult clinical problem to address, but that symptoms often resolve.
  • If there is a microbiologically or clinically documented failure with persistent urethritis, consider the following:
    • Re-exposure to untreated partner.
    • Infection acquired from new partner.
    • Medication not taken correctly/not completed.
    • Infection with other pathogens.
    • Presence of resistant organisms.Footnote 20
    • Other causes (e.g., urinary tract infection, prostatitis, phimosis, chemical irritation, urethral strictures, tumours).
  • Consider:
    • Repeat specimens (urine and endourethral) for Gram stain, culture and NAAT for N. gonorrhoeae and C. trachomatis.
    • Endourethral swabs or urine for T vaginalis.Footnote 2,Footnote 21
    • Endourethral swab or urine for herpes simplex virus culture, although usually associated with lesions.Footnote 3,Footnote 22
    • Endourethral specimen or first-void urine for culture for U urealyticum and M genitaliumFootnote 5 (usually at a specialized laboratory).
    • Urology or infectious diseases consultation if unresolved.
    • Determine whether other underlying etiologies, such as anxiety, contribute to symptoms.
Children with urethritis
  • Sexual abuse must be considered if there are symptoms of unexplained pyuria in prepubertal boys or young males who are not sexually active (see Sexual Abuse in Peripubertal and Prepubertal Children chapter).
  • Practitioners need to follow provincial guidelines for reporting any suspected cases of child sexual abuse to appropriate authorities.
  • All persons named as suspects in child sexual abuse cases should be located and clinically evaluated; prophylactic treatment may or may not be offered and the decision to treat or not should be based on history, clinical findings and test results (see Sexual abuse in Peripubertal and Prepubertal Children chapter).
  • Young men and women with urethritis may be erroneously diagnosed with urinary tract infections.
  • In addition to symptoms present in adults, children with urethritis can also demonstrate the following:
    • Abdominal pain.
    • Unwillingness to void.
    • Enuresis.
  • For treatment regimens in children, see Gonococcal Infections and Chlamydial Infections chapters.
  • Repeat testing should be offered to all children.
Urethritis in women
  • Urethritis caused by N. gonorrhoeae and C. trachomatis in women can occur without cervicitis.
  • Dysuria and urinary frequency may be symptoms of urethritis and thus may mimic cystitis.
  • Specimens for C. trachomatis and N. gonorrhoeae in women should be obtained from both urine and endocervical specimens.

Figure 1. Urethritis TreatmentFigure 1 - Footnote * Flow Chart

Figure 1
Text Equivalent - Figure 1

Figure 1 is an algorithm to guide treatment of a patient presenting with symptoms of urethritis or who is at risk of an infection. Guidance for specimen collection is provided elsewhere in the guidelines (in chapter entitled Laboratory Diagnosis of Sexually Transmitted Diseases).

Four treatment scenarios are presented, depending on whether the patient has urethral discharge or not, and whether Gram stain results are available or not.

Within each scenario, practitioners are guided towards one treatment option or another, depending on the risk of infection, the risk of loss-to-follow-up; and Gram stain results (if available).

Scenario 1: If the patient has urethral discharge and Gram stain results are not available

Depending on whether the patient is at high risk for infection AND loss-to-follow up or not, there are two possible courses of action:

If at risk of STI AND loss-to-follow-up, treat for gonococcal urethritis with:

Cefixime 400 mg orally in a single dose (or alternate medication, as described in the Gonococcal Infections chapter of the guidelines) PLUS EITHER Doxycycline 100 mg orally twice per day for seven days, OR, if poor compliance is expected, Azithromycin 1 gm. orally in a single dose (or alternate regimen, as outlined in the Chlamydial Infections chapter);

OR

If not at high risk for infection or loss-to-follow-up, treat for non-gonococcal urethritis with:

Doxycycline 100 mg orally twice per day for seven days, OR, if poor compliance is expected, Azithromycin 1 gm orally in a single dose (or alternate regimen, as outlined in the Chlamydial Infections chapter).

IN ADDITION, treatment for gonorrhea can be considered if the local prevalence is high OR the prevalence is high in the region where contact occurred.

Scenario 2: If the patient has urethral discharge AND Gram stain results are available

Depending on Gram stain results, there are three possible courses of action.

The first possibility is that results show a mean of more than five polymorphonuclear leukocytes per field (x 1000) in five non-adjacent fields AND Gram-negative intracellular diplococci, OR Gram-negative intracellular diplococci alone.

In this case, treat for gonococcal urethritis with:

Cefixime 400 mg orally in a single dose (or alternate medication, as described in the Gonococcal Infections chapter of the guidelines) PLUS EITHER Doxycycline 100 mg orally twice per day for seven days, OR, if poor compliance is expected, Azithromycin 1 gm orally in a single dose (or alternate regimen, as outlined in the Chlamydial Infections chapter).

The second possibility is that results show a mean of more than five polymorphonuclear leukocytes per field (x 1000) in five non-adjacent fields AND no Gram-negative intracellular diplococcic.

In this case, treat for non-gonococcal urethritis with:

Doxycycline 100 mg orally twice per day for seven days OR, if poor compliance is expected, Azithromycin 1 gm orally in a single dose (or alternate regimen, as outlined in the Chlamydial Infections chapter).

IN ADDITION, treatment for gonorrhea can be considered if the local prevalence is high OR the prevalence is high in the region where the contact occurred.

The third possibility is that results show a mean of 5 polymorphonuclear leukocytes per field or less.

In this case, determine if the patient is at high risk for infection AND loss-to-follow-up.

AND depending on whether the patient is at high risk for infection AND loss-to-follow-up or not, there are two possible courses of action:

If at risk of STI AND loss-to-follow-up, treat for gonococcal urethritis with:

Cefixime 400 mg orally in a single dose (or alternate medication, as described in the Gonococcal Infections chapter of the guidelines) PLUS EITHER Doxycycline 100 mg orally twice per day for seven days, OR, if poor compliance is expected, Azithromycin 1 gm orally in a single dose (or alternate regimen, as outlined in the Chlamydial Infections chapter).

OR

If not at high risk for infection OR loss-to-follow-up, defer treatment until laboratory results are available;

AND

If positive, treat according to recommendations in the appropriate chapter.

Scenario 3: If the patient has no urethral discharge AND Gram stain results are not available

Depending on whether the patient is at high risk for infection AND loss-to-follow-up or not, there are two possible courses of action:

If at high risk of STI AND loss-to-follow-up, treat for gonococcal urethritis with:

Cefixime 400 mg orally in a single dose (or alternate medication, as described in the Gonococcal Infections chapter of the guidelines) PLUS EITHER Doxycycline 100 mg orally twice per day for seven days, OR, if poor compliance is expected, Azithromycin 1 gm orally in a single dose. (or alternate regimen, as outlined in the Chlamydial Infections chapter);

OR

If not at high risk for infection OR loss-to-follow-up, defer treatment until laboratory results are available;

AND

If positive, treat according to recommendations in the appropriate chapter.

Scenario 4: If the patient has no urethral discharge AND Gram stain results are available

Depending on Gram stain results, there are three possible courses of action.

The first possibility is that results show a mean of more than five polymorphonuclear leukocytes per field (x 1000) in five non-adjacent fields AND Gram-negative intracellular diplococci, OR Gram-negative intracellular diplococci alone.

In this case, treat for gonococcal urethritis with:

Cefixime 400 mg orally in a single dose (or alternate medication, as described in the Gonococcal Infections chapter of the guidelines) PLUS EITHER Doxycycline 100 mg orally twice per day for seven days, OR, if poor compliance is expected, Azithromycin 1 gm orally in a single dose. (or alternate regimen, as outlined in the Chlamydial Infections chapter).

The second possibility is that results show a mean of more than five polymorphonuclear leukocytes per field (x 1000) in five non-adjacent fields AND no Gram-negative intracellular diplococci.

In this case, treat for non-gonococcal urethritis with:

Doxycycline 100 mg orally twice per day for seven days OR, if poor compliance is expected, Azithromycin 1 gm orally in a single dose (or alternate regimen, as outlined in the Chlamydial Infections chapter).

IN ADDITION, treatment for gonorrhea can be considered if the local prevalence is high OR the prevalence is high in the region where contact occurred.

The third possibility is that results show a mean of 5 polymorphonuclear leukocytes per field or less.

In this case determine if the patient is at high risk for infection AND loss-to-follow-up;

AND depending on whether the patient is at high risk for infection AND loss-to-follow up or not, there are two possible courses of action:

If at high risk of STI AND loss-to-follow-up, treat for gonococcal urethritis with:

Cefixime 400 mg orally in a single dose (or alternate medication, as described in the Gonococcal Infections chapter of the guidelines) PLUS EITHER Doxycycline 100 mg orally twice per day for seven days, OR, if poor compliance is expected, Azithromycin 1 gm orally in a single dose. (or alternate regimen, as outlined in the Chlamydial Infections chapter);

OR

If not at high risk for infection OR loss-to-follow-up, defer treatment until laboratory results are available;

AND

If positive, treat according to recommendations in the appropriate chapter.

PMN
polymorphonuclear leukocytes
*Treatment flow chart only. Specimens to be collected and sent for laboratory testing as outlined in the Diagnosis section.
A mean of ≥5 PMNs per field (x 1000) in five non-adjacent fields.
Ψ
Treat for urethritis due to chlamydia, consider treating for gonorrhea IF local prevalence is high or if sexual contact occurred in a region with high prevalence OR if follow up is not assured OR if partner is infected.
For alternative regimens, see Gonococcal Infections chapter.
§
For alternative regimens, see Chlamydial Infections chapter.

References

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