No 628009

Initiating diagnostic measures and pharmacological treatment in a male with urethral discharge

Developed in collaboration with an advisory committee consisting of Québec clinicians and experts. Validated by the Comité d’excellence clinique en usage optimal du médicament, des protocoles médicaux nationaux et ordonnances of the Institut national d’excellence en santé et en services sociaux (INESSS). CLINICAL SITUATION OR TARGET POPULATION Symptomatic male:

 A sexually active male with a mucoid, mucopurulent or purulent urethral discharge1 with or without urethral discomfort or burning on urination CONTRAINDICATIONS TO THE APPLICATION OF THIS PROTOCOL Symptomatic male:

 < 14 years of age  Immunocompromised state2  Urological intervention in the past month (e.g., a prostate biopsy, a cystoscopy or a urinary catheter)  The presence of a contraindication to the use of a recommended drug, with no appropriate alternative  Three or more episodes of urethral discharge in the past 6 months INSTRUCTIONS

1. PRECAUTIONS For a victim of sexual assault, also follow the recommendations in the Guide d’intervention médicosociale.

2. HEALTH STATUS ASSESSMENT

2.1 Presence of signs and symptoms Look for and characterize the following:

 Mucoid, purulent or mucopurulent urethral discharge  Urethral discomfort  Burning on urination Look for the following:  Suprapubic, testicular or perianal pain or pain during ejaculation  Urinary frequency, vesical tenesmus, hematuria, nocturia or urgency  Fever  Signs and symptoms of a sexually transmitted and blood-borne infection (STBBI) at other sites of exposure (pharynx or rectum)

2.2 Medical history

 Date and results of last STBBI screening test  STBBI history

1 Urethral discharge reported by the patient or observed by the health professional. 2 Examples of possible causes of an immunocompromised state (see Appendix V of the Guide québécois de dépistage des ITSS): congenital immune deficiency, leukemia, lymphoma, multiple myeloma, nonhematologic cancer, acquired immune deficiency (such as during HIV infection), hemodialysis, and the use of immunosuppressants.

INESSS | Quebec’s medical protocol – Urethral discharge 1

2.3 Medication history

 Medication use  Drug allergies

2.4 STBBI risk factors

 Inquire about STBBI risk factors and assess the indications for STBBI screening. Consult the tool ITSS à rechercher selon les facteurs de risque décelés.

3. PHYSICAL EXAMINATION

3.1 Overall health and vital signs Take temperature, if warranted.

3.2 Inspection of external genitalia Inspect the external genitalia, the urethral meatus and the perinanal region. Palpate the inguinal lymph nodes, the scrotum, the testicles and the epididymis. If the patient is not circumcised, pull back the prepuce to inspect the glans penis. The patient or the clinician will need to induce the urethral discharge to make it more visible. Look for:

 A mucoid, purulent or mucopurulent urethral discharge or urethral meatus erythema.  Epididymal or testicular tenderness on palpation or palpable epididymal swelling.  Scrotal erythema or edema or scrotal masses.  Skin or anogenital lesions.  Lymphadenopathy.

4. INVESTIGATION

4.1 Specimens and microbiological tests Obtain the following:  A urine specimen to screen for C. trachomatis and N. gonorrhoeae by nucleic acid amplification testing (NAAT) AND  A specimen of urethral secretions for an N. gonorrhoeae culture. If there are signs or symptoms of pharyngeal or rectal infection3, obtain a pharyngeal or rectal specimen (depending on the location of the symptoms) to screen for C. trachomatis and N. gonorrhoeae by NAAT and a specimen for an N. gonorrhoeae culture.

In the case of pharyngeal or rectal exposure with no signs or symptoms at these sites, consult the tool Prélèvements et analyses recommandés en fonction de l’infection recherchée chez les personnes asymptomatiques (dépistage).

If the patient has risk factors for other STBBIs:  Determine the STBBIs to screen for in accordance with the tool ITSS à rechercher selon les facteurs de risque décelés.  Obtain the specimen or specimens to screen for the other STBBIs to be checked for according to the tool Prélèvements et analyses recommandés en fonction de l’infection recherchée chez les personnes asymptomatiques (dépistage).

3 The presence of signs or symptoms of pharyngeal or rectal infection is not a contraindication to the application of this protocol, but rather a constraint or situation requiring a mandatory medical consultation (see Section 6). As indicated in Section 4.1, pharmacological treatment can be initiated, and the patient can then be referred to the responding physician. In such case, a pharyngeal or rectal specimen is considered a prereferral specimen.

INESSS | Quebec’s medical protocol – Urethral discharge 2

4.2 Details concerning specimens Regardless of type of specimen, it is important to consult the laboratory at the facility concerned for details on the tests used locally (e.g., suitable specimen collection sites, the types of specimens accepted, the applicable specimen collection conditions, storage and transport).

5. THERAPEUTIC APPROACH IN THE PRESENCE OF A MUCOID, PURULENT OR MUCOPURLENT URETHRAL DISCHARGE 5.1 Treatment indication

If there is a mucoid, purulent or mucopurlent urethral discharge, initiate pharmacological treatment without waiting for the microbiological test results.

Details:  Initiate pharmacological treatment even if there are signs or symptoms at other sites of exposure (pharynx or rectum) and then refer the patient to the responding physician.

5.2 Preventive interventions, pharmacological treatment and follow-up Consult the optimal usage guide STBBI – Syndromic approach (urethritis)

6. FOLLOW-UP Inquire about adverse effects and monitor the patient for potential interactions with other drugs or substances. Check if the signs and symptoms persist beyond 7 days after the start of treatment. Order a test of cure in accordance with the recommendations in the optimal usage guide STBBI – Uncomplicated Chlamydia trachomatis or Neisseria gonorrhoeae infection.

INESSS | Quebec’s medical protocol – Urethral discharge 3

7. SITUATIONS NECESSITING A SUPPLEMENTARY INVESTIGATION At the time of the evaluation  Fever  Suprapubic, testicular or perianal pain or pain during ejaculation  The following signs noted during the physical examination: epididymal or testicular tenderness on palpation, palpable epididymal swelling, erythema or edema of the scrotum, scrotal masses, skin lesions, anogenital lesions, lymphadenopathy  Signs or symptoms at other sites of exposure  Signs or symptoms suggestive of a urinary tract infection: urinary frequency, vesical tenesmus, hematuria, nocturia and urgency

The following table contains a summary of the specimens to be collected (prereferral specimens) before referring a male in one or more situations requiring, at the time of the evaluation, a mandatory medical consultation with the responding physician based on the existence of certain conditions.

CONDITIONS SPECIMENS TO BE OBTAINED BEFORE REFERRING THE PATIENT TO THE (MORE THAN ONE CONDITION MAY APPLY) RESPONDING PHYSICIAN Risk factors for C. trachomatis or N. • Urine specimen to screen for C. trachomatis and N. gonorrhoeae by NAAT AND gonorrhoeae infection AND urethral discharge • Specimen of urethral secretions for an N. gonorrhoeae culture Risk factors for C. trachomatis or N. Pharyngeal or rectal specimen (depending on the location of the symptoms) to screen for gonorrhoeae infection AND signs or symptoms C. trachomatis and N. gonorrhoeae by NAAT and a specimen for an N. gonorrhoeae culture of pharyngeal or rectal infection Risk factors for C. trachomatis or N. Consult the tool Prélèvements et analyses recommandés en fonction de l’infection recherchée gonorrhoeae infection AND pharyngeal or rectal chez les personnes asymptomatiques (dépistage) exposure with no signs or symptoms at these sites Signs or symptoms suggestive of a urinary tract Urine specimen for urinalysis and urine culture infection (urinary frequency, vesical tenesmus, hematuria, nocturia and urgency) • Specimen for a viral identification test for the herpes simplex virus (HSV)5 AND Anogenital ulceration4 • Syphilis serology

During or after treatment:  Intolerance to the medication  Persistence of signs or symptoms 7 days after the start of treatment  Signs or symptoms of urethritis that reappear within the 6 weeks following the start of treatment after having first resolved Microbiological test results:  Positive screening test results for other STBBIs  Screening test results for C. trachomatis and N. gonorrhoeae: - Negative (C. trachomatis and N. gonorrhoeae not present): refer patient to the responding physician only if he is still symptomatic when the result is received; - Positive at other sites (pharynx or rectum): if the nurse does not have the right to prescribe for the purpose of applying the Protocole national pour le traitement d'une infection à C. trachomatis ou à N. gonorrhoeae chez une personne asymptomatique, refer the patient to the responding physician; - Positive for C. trachomatis with an LGV genotype.  Test of cure positive for C. trachomatis or N. gonorrhoeae

4 If anogenital ulceration and STBBI risk factors, request on the requisition that tests be performed to screen for the LGV (lymphogranuloma venereum) genotype if the urine (or rectal, if applicable) NAAT results are positive for C. trachomatis. 5 Unless the patient had a viral identification test (culture or NAAT) result that was positive for HSV in the past. Obtaining a specimen early (as soon as lesions appear) is essential for detecting HSV.

INESSS | Quebec’s medical protocol – Urethral discharge 4

8. DECISION ALGORITHM

INESSS | Quebec’s medical protocol – Urethral discharge 5

DEVELOPMENT PROCESS

The development process is based on the triangulation of several data sources, including best clinical practice recommendations and contextual and experiential data. Two systematic reviews were conducted separately of clinical practice guidelines, consensus reports and health technology assessment reports published between 2011 and 2017. To take current Canadian and Quebec practice into account, the Canadian Guidelines on Sexually Transmitted Infections were selected as well, even if they were published in 2010. Documentation from regulatory agencies or prepared by associations, organizations or professional orders, pharmaceutical product monographs and Health Canada advisories were also consulted. The methodology used to conduct this literature review meets INESSS’s production standards. The data analysis was performed from a contextualizaton perspective regarding practice in Québec, using experiential data obtained from the health professionals on the advisory committee and the members of the INESSS project team. INESSS assumes full responsibility for the final form and contents of this medical protocol. The recommendations it contains do not necessarily reflect the opinions of the persons consulted for the purposes of developing this protocol. INESSS advisory committee: Dr. Serge Carrier, Urologist Danielle Gourde, Pharmacist Dr. Annie-Claude Labbé, Microbiologist and Infectious Disease Specialist Dr. Thierry Lebeau, Urologist Éric Lefebvre, Nurse Clinician Dr. Stéphane Roy, Family Physician Dr. Marc Steben, Family Physician Dr. Sylvie Venne, Family Physician Chana Wittenberg, Nurse Clinician

Validated by INESSS’s CEC-UOM-PMNO.

INESSS | Quebec’s medical protocol – Urethral discharge 6

REFERENCES

Agence de la santé publique du Canada (ASPC). Lignes directrices canadiennes (LDC) sur les infections transmissibles sexuellement -Traitement des infections gonococciques par suite du retrait du marché de la spectinomycine: .׃ Déclaration d’orientation pour les traitements de remplacement. Ottawa, ON, Canada 2017

Agence de la santé publique du Canada (ASPC). Lignes directrices canadiennes (LDC) sur les infections transmissibles sexuellement - Déclaration supplémentaire concernant les recommandations liées au diagnostic, à la prise en .׃ charge et au suivi de l’épididymite, 2014. Ottawa, ON, Canada 2014

Agence de la santé publique du Canada (ASPC). Lignes directrices canadiennes (LDC) sur les infections transmissibles sexuellement - Déclaration supplémentaire concernant les recommandations liées au diagnostic, à la prise en .׃ charge et au suivi de l’urétrite. Ottawa, ON, Canada 2014

Agence de la santé publique du Canada (ASPC). Lignes directrices canadiennes (LDC) sur les infections transmissibles .׃ sexuellement - Chapitre : Infections gonococciques. Ottawa, ON, Canada 2013

Agence de la santé publique du Canada (ASPC). Zithromax/Zmax SR (azithromycine) - Risque de battements de cœur Disponible .׃ irréguliers pouvant entraîner la mort - Pour les professionnels de la santé Ottawa, ON, Canada 2013 .http://canadiensensante.gc.ca/recall-alert-rappel-avis/hc-sc/2013/29199a-fra.php ׃ à

Agence de la santé publique du Canada (ASPC). Lignes directrices canadiennes (LDC) sur les infections transmissibles .׃ sexuellement. Ottawa, ON, Canada 2010

Agence de la santé publique du Canada (ASPC). Renseignements importants en matière d'innocuité émis par Santé ׃ Disponible à .׃ Canada concernant Ceftriaxone - Avis aux hôpitaux. Ottawa, ON, Canada 2009 http://canadiensensante.gc.ca/recall-alert-rappel-avis/hc-sc/2009/14535a-fra.php.

Agence de la santé publique du Canada (ASPC). Interactions fatales entre la ceftriaxone et le calcium - Avis aux -http://canadiensensante.gc.ca/recall-alert-rappel-avis/hc ׃ Disponible à .׃ hôpitaux. Ottawa, ON, Canada 2008 sc/2008/14497a-fra.php.

Agence de la santé publique du Canada (ASPC). Base de données sur les produits pharmaceutiques (BDPP) Ottawa, .http://www.hc-sc.gc.ca/dhp-mps/prodpharma/databasdon/index-fra.php ׃ ON, Canada. Disponible à

Agence française de sécurité sanitaire des produits de santé (HAS). Traitement des urétrites et cervicites non .׃ compliquées. Saint-Denis La Plaine, France 2015

BC Center for disease control (BCCDC). British Columbia Treatment Guidelines - Sexually Transmitted Infections in .2014 ׃ Adolescents and Adults. Vancouver, BC, Canada

British Association for Sexual Health and HIV (BASHH). UK National guideline for the management of infection with .2015 ׃ Chlamydia trachomatis. Macclesfield, Cheshire, Royaume-Uni

British Association for Sexual Health and HIV (BASHH). UK National guideline on the management of non-gonococcal .2015 ׃urethritis. Macclesfield, Cheshire, Royaume-Uni

British Association for Sexual Health and HIV (BASHH). UK national guideline for the management of gonorrhoea in .2011 ׃ adults. Macclesfield, Cheshire, Royaume-Uni

Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2015. MMWR .Jun 05 .2015 ׃ Recomm Rep. 2015/06/05 éd. Atlanta, Georgia, États-Unis

College of registered nurses of British Colombia (CRNBC). CRNBC certified practice decision support tools (DSTs) - Adult .2016 ׃ lower urinary tract infection. Vancouver, BC, Canada

College of registered nurses of British Colombia (CRNBC). CRNBC certified practice decision support tools (DSTs) - .2014 ׃ Gonorrhea (reportable). Vancouver, BC, Canada

INESSS | Quebec’s medical protocol – Urethral discharge 7

College of registered nurses of British Colombia (CRNBC). CRNBC certified practice decision support tools (DSTs) - .2014 ׃ Chlamydia trachomatis (reportable). Vancouver, BC, Canada

College of registered nurses of British Colombia (CRNBC). CRNBC certified practice decision support tools (DSTs) - .2014 ׃ Urethritis (male). Vancouver, BC, Canada

College of registered nurses of British Colombia (CRNBC). CRNBC certified practice decision support tools (DSTs) - .2014 ׃ Recurrent urethritis (male). Vancouver, BC, Canada

.2015 ׃ European Association of Urology (EAU). Guidelines on Urological Infections. Arnhem, Pays-Bas

European guideline International Union against sexually transmitted infections (IUSTI). 2015 European guideline on the management of Chlamydia trachomatis infections. Int J STD AIDS 2016;27(5):333-48.

European guideline International Union against sexually transmitted infections (IUSTI). 2016 European Guideline on the .2016 ׃ management of non-gonococcal urethritis. Southampton, Royaume-Uni

European guideline International Union against sexually transmitted infections (IUSTI). 2016 European guideline on the .2016 ׃ management of epididymo-orchitis. European guideline for the management of balanoposthitis

European guideline International Union against sexually transmitted infections (IUSTI). 2013 European guideline for the .2013 ׃ management of balanoposthitis. Southampton, Royaume-Uni

European guideline International Union against sexually transmitted infections (IUSTI). 2012 European guideline on the .׃ Diagnosis and Treatment of Gonorrhoea in Adults. Southampton, Royaume-Uni 2012

Institut national d’excellence en santé et en services sociaux (INESSS). Guide d’usage optimal sur le traitement des infections non compliquées à Chlamydia trachomatis ou à Neisseria gonorrhoeae. Québec, Qc : INESSS; mise à jour avril 2018.

Institut national d’excellence en santé et en services sociaux (INESSS). Guide d’usage optimal sur l’approche syndromique : cervicite et urétrite, épididymite/orchi-épididymite, atteinte inflammatoire pelvienne (AIP) et rectite. Québec, Qc : INESSS; mise à jour avril 2018.

Institut national d’excellence en santé et en services sociaux (INESSS). Guide clinique en antibiothérapie-Infection .׃ urinaire chez l’adulte. Québec, Qc, Canada 2017

Ministère de la Santé et des Services sociaux du Québec (MSSS). Guide québécois de dépistage des infections .2017 ׃ transmissibles sexuellement et par le sang. Québec, Qc, Canada

Scottish Intercollegiate Guidelines Network (SIGN). Management of suspected bacterial urinary tract infection in adults. .׃ Edinburgh, Royaume-Uni 2012

Société de Pathologie Infectieuse de Langue Française(SIPLF). Infections urinaires bactériennes communautaires de .׃ l'adulte - diagnostic et antibiothérapie. Paris, France 2015

INESSS | Quebec’s medical protocol – Urethral discharge 8