Interim guidance for the treatment of uncomplicated gonococcal infections

An Advisory Committee Statement (ACS)

National Advisory Committee on Sexually Transmitted and Blood-Borne Infections (NAC-STBBI)

Interim guidance for the treatment of uncomplicated gonococcal infections

Note: The full statement is being translated into French; it will be published as soon as possible. For questions, please contact the NAC-STBBI Secretariat at sti.secretariat-its@phac-aspc.gc.ca

Preamble

The National Advisory Committee on Sexually Transmitted and Blood-Borne Infections (NAC-STBBI) is an External Advisory Body that provides the Public Health Agency of Canada (PHAC) with ongoing scientific and public health advice and recommendations for the development of sexually transmitted and blood-borne infections (STBBI) guidance, in support of its mandate to prevent and control infectious diseases in Canada.

PHAC acknowledges that the advice and recommendations in this statement are based upon the best available scientific knowledge at the time of writing and is disseminating this document for information purposes to primary care providers and public health professionals. The NAC-STBBI Statement may also assist policy makers or serve as the basis for adaptation by other guideline developers. NAC-STBBI members and liaison members conduct themselves within the context of PHAC's Policy on Conflict of Interest, including yearly declaration of interests and affiliations.

The recommendations in this statement do not supersede any provincial/territorial legislative, regulatory, policy and practice requirements or professional guidelines that govern the practice of health professionals in their respective jurisdictions, whose recommendations may differ due to local epidemiology or context. The recommendations in this statement may not reflect all the situations that may arise in professional practice and are not intended as a substitute for clinical judgment in consideration of individual circumstances and available resources.

Executive summary

Background

Gonococcal infection, caused by Neisseria gonorrhoeae (NG), represents a significant public health problem globally due to antimicrobial resistance (AMR), the potential for serious complications when left undiagnosed and untreated, as well as its association with HIV transmission and acquisition. There has been a steady increase in reported NG infection cases since 1997. Between 2010 and 2019 in Canada, the rates have almost tripled. In 2019, the national rate was 94.3 cases per 100,000 populationFootnote 1.

Rationale for the guidelines

Increasing AMR in NG, considerable variability in the treatment regimens recommended by PHAC and other guideline development groups, and increasing rates of gonococcal infection prompted the NAC-STBBI to prioritize the review and update of PHAC's previous preferred treatment recommendation for uncomplicated NG infection in adults and adolescents 10 years of age and older. This update takes into consideration patient values and preferences, impact on healthcare providers and realities of health care system including access to culture for NG, access to injectable drugs on site and costs.

Objectives

The objectives of this work are:

The recommendations included herein consist of an interim guidance; the final recommendations will be available after the completion of a review of primary studies currently underway.

Methods

A Working Group composed of experts from NAC-STBBI was formed and the recommendations were developed following the methodology for developing recommendations by NAC-STBBI and PHACFootnote 2Footnote 3Footnote 4Footnote 5. PHAC in collaboration with the Working Group conducted a scoping exercise (a review) of relevant guidelines and systematic reviews on treatment for uncomplicated gonorrhea in symptomatic or asymptomatic adults and adolescentsFootnote 6, to support the development of the recommendations. Although a systematic review of the literature was not undertaken, a sample of primary studies were identified and considered. In addition, a targeted search of the literature was performed for evidence on patient values and preferences, feasibility, acceptability, equity and resource use.

Latest available data on notified cases of NG infections, AMR, and treatment failures Footnote 7Footnote 8Footnote 9 were considered in the development of the treatment recommendations. Other types of evidence were also considered, including expert opinion and pharmacokinetics (PK) and pharmacodynamics (PD) published studiesFootnote 10Footnote 11. Conflicts of interest were managed according to PHAC guidelines; no conflicts were declared prior to discussion and voting on the recommendations. External peer-reviewers (outside of NAC-STBBI) with expertise in infectious diseases were identified and engaged prior to the publication of the recommendations.

Summary recommendations

This statement provides recommendations 1) on preferred treatment for uncomplicated NG infection in adults and adolescents 10 years of age and older (Table 1); 2) for the choice of test and timing for NG TOC (Table 2); and 3) for requesting culture to obtain NG antimicrobial susceptibility (Table 3).

Table 1: Updated recommendation on the preferred treatment of uncomplicated gonorrhea in adults and adolescents 10 years of age and older

NAC-STBBI suggests ceftriaxone 500 mg IM as a single dose (monotherapy) for preferred treatment of all uncomplicated infections (urethral, endocervical, vaginal, rectal and pharyngeal).
(conditional recommendation, low certainty of evidence).

Alternative treatment options, which are required if access to IM injection is not available, if the individual refuses the injection, or if the individual is severely allergic to cephalosporins, are currently under review by the NAC-STBBI. Refer to the following four alternative treatment regimens in the PHAC Gonorrhea Guide pending further review.

  • Cefixime 800 mg PO in a single dose plus doxycycline 100 mg PO BID x 7 daysFootnote *
  • Cefixime 800 mg PO in a single dose plus azithromycin 1g PO in a single dose
  • Azithromycin 2 g PO in a single dose PLUS gentamicin 240 mg IM in a single doseFootnote *
  • Gentamicin 240 mg IM in a single dose PLUS doxycycline 100 mg PO twice daily for 7 daysFootnote *

Notes:

  • If trachomatis infection has not been excluded by a negative test, concurrent treatment for chlamydia is recommended; refer to the treatment recommendations in the PHAC Chlamydia and LGV Guide: Treatment and follow-up).
  • Refer to PHAC Gonorrhea Guide: Treatment and follow-up for further details for each alternative treatment regimen, including the indications for use of ertapenem and also for information on partner notification and treatment.
  • Test of cure (TOC) is recommended for all positive NG sites in all cases (refer to Table 2 below).
  • The following alternative treatment regimens have been removed from the PHAC Gonorrhea Guide.
    • Ceftriaxone 250 mg IM in a single dose PLUS doxycycline 100 mg PO BID x 7 daysFootnote **
    • Azithromycin 2 g in a single oral dose PLUS ciprofloxacin 500 mg in a single oral doseFootnote **
    • Azithromycin 2 g in a single dose plus gemifloxacin 320 mg in a single oral doseFootnote **

Table 2: Recommendation on the choice of test and timing for test of cure

NAC-STBBI recommends a TOC for all positive NG sites in all cases. This is particularly important when regimens other than ceftriaxone 500 mg IM are used.

  • For asymptomatic individuals, a NAAT should be performed three to four weeks after the completion of treatment because residual nucleic acids from dead bacteria may be responsible for positive results less than three weeks after treatment.
  • When a TOC is performed within three weeks after completion of treatment, a culture should be performed; samples should be taken at least three days after completion of treatment.
  • When treatment failure is suspected more than three weeks after treatment, both NAAT and culture should be performed (for example, when symptoms persist or recur after treatment).

Table 3: Recommendation on NG culture

Although culture is less sensitive than NAAT, it provides the opportunity for antimicrobial susceptibility determination, which is important for case management and is critical for monitoring AMR patterns and trends.

NAC-STBBI recommends NG culture (together with NAAT) in the following situations:

  • For a TOCFootnote * failure is suspected;
  • In the presence of symptoms compatible with cervicitis, urethritis, pelvic inflammatory disease (PID), epididymo-orchitis, proctitis or pharyngitis;
  • In pregnant individuals;
  • When an asymptomatic individual is notified as a contact of an NG infected case;
  • When sexual abuse/sexual assault is suspected (this may vary according to legal and medical contexts of the jurisdiction);
  • If the infection might have been acquired in countries or areas with high rates of AMR (NG resistant strains have been reported in Canada, Japan, Europe and Australia; many were associated with travel to South-East Asia).

In addition, NAC-STBBI recommends a culture when NG infection is confirmed by NAAT only, as long as it does not delay treatment.

Note:

  • Successful culture requires proper collection and transportation of appropriate specimens. Consult with your local Public Health Laboratory for guidance on specimen collection and transportation.

Acknowledgements

NAC-STBBI Gonorrhea Treatment Working Group:
Co-Chairs: Annie-Claude Labbé and Tim Lau
Members: Jared Bullard, Troy Grennan, Todd F. Hatchette, Irene Martin, Petra Smyczek and Mark Yudin

Other NAC-STBBI members:
Ian M. Gemmill (chair), William A. Fisher, Jennifer Gratrix, Gina Ogilvie and Marc Steben
Ex-officio representative (non-voting): Ibrahim Khan

Public Health Agency of Canada (Secretariat)
Ulrick Auguste, Shamila Shanmugasegaram, Annie Fleurant and Nick Giannakoulis

External Contributor
Nancy Santesso (McMaster University)

External Peer-reviewers

References

Footnote 1

Public Health Agency of Canada. Report on Sexually Transmitted Infection Surveillance in Canada, 2019. 2021.Cat.: HP37-10E-PDF ISBN: 1923-2977 Pub.: 210348. Available at:https://www.canada.ca/content/dam/phac-aspc/documents/services/publications/diseases-conditions/report-sexually-transmitted-infection-surveillance-canada-2019/pub1-eng.pdf. Accessed 7 June 2023.

Return to footnote 1 referrer

Footnote 2

Public Health Agency of Canada. Methods Manual for the Public Health Agency of Canada Sexually Transmitted and Blood-Borne Infections Recommendations. 2019 (updated in 2021): Internal PHAC document prepared by Shanmugasegaram, S (Unpublished).

Return to footnote 2 referrer

Footnote 3

Public Health Agency of Canada. Interim and Rapid Advice Guideline Methodology Section in the Methods Manual for the Public Health Agency of Canada Sexually Transmitted and Blood-Borne Infections Recommendations. 2019 (updated in 2023): Internal PHAC document prepared by Shanmugasegaram, S (Unpublished).

Return to footnote 3 referrer

Footnote 4

Shanmugasegaram S, Gale-Rowe M. Methodology for developing the Public Health Agency of Canada Sexually Transmitted and Blood-Borne Infections Guidelines [Abstract]. Cochrane Colloquium. Toronto, ON. October. Advances in Evidence Synthesis: Special Issue. Cochrane Database of Systematic Reviews. 2020;9(Suppl. 1):226. Available at: https://abstracts.cochrane.org/2020-abstracts/methodology-developing-public-health-agency-canada-sexually-transmitted-and-blood. Accessed 29 February 2024.

Return to footnote 4 referrer

Footnote 5

Shanmugasegaram S, Gadient S, Gale-Rowe M. Translating evidence into practice with the National Advisory Committee on Sexually Transmitted and Blood-Borne Infections. Can Commun Dis Rep. 2020;46(11/12):398-402. Available at: https://doi.org/10.14745/ccdr.v46i1112a06. Accessed 29 February 2024.

Return to footnote 5 referrer

Footnote 6

Public Health Agency of Canada. Monotherapy versus combination therapy in the treatment of uncomplicated gonococcal infections in adults and adolescents: a scoping exercise. 2020: Internal PHAC document (Unpublished).

Return to footnote 6 referrer

Footnote 7

Thorington R, Sawatzky P, Lefebvre B, Diggle, M, Hoang, L, Samir P, et al. Antimicrobial susceptibilities of Neisseria gonorrhoeae in Canada, 2020. Canada Commun Dis Rep. 2022;48(11/12):571-579. doi:10.14745/ccdr.v48i1112a10

Return to footnote 7 referrer

Footnote 8

Lefebvre B, Labbé, A-C. Sommaire des résultats d'antibiorésistance des souches Neisseria gonorrhoeae au Québec en 2021 (inspq.qc.ca). Available at : https://www.inspq.qc.ca/sites/default/files/lspq/3290-antibioresistance-souches-neisseria-gonorrhoeae-2021.pdf. Accessed 07/07, 2023.

Return to footnote 8 referrer

Footnote 9

Public Health Agency of Canada. Report on the Enhanced Surveillance of Antimicrobial-Resistant Gonorrhea (ESAG): Results from 2015 to 2017. 2021. Available at : https://www.canada.ca/content/dam/phac-aspc/documents/services/publications/diseases-conditions/2015-2017-report-enhanced-surveillance-antimicrobial-resistant-gonorrhea/esag-2015-2017-eng.pdf

Return to footnote 9 referrer

Footnote 10

Chisholm SA, Mouton JW, Lewis DA, et al. Cephalosporin MIC creep among gonococci: time for a pharmacodynamic rethink? J Antimicrob Chemother 2010; 65:2141-2148.

Return to footnote 10 referrer

Footnote 11

Connolly KL, Eakin AE, Gomez C et al. Pharmacokinetic data are predictive of in vivo efficacy for cefixime and ceftriaxone against susceptible and resistant Neisseria gonorrhoeae strains in the gonorrhea mouse model. Antimicrob Agents Chemother 2019;63:e01644-18.

Return to footnote 11 referrer

Page details

Date modified: