Recommendations on the use of prophylactic doxycycline for the prevention of bacterial STI (chlamydia, gonorrhea, syphilis)

An Advisory Committee Statement (ACS)

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

Date published: November 2025

On this page

• Preamble
• Executive summary
  • Background
  • Rationale for guidelines
• Objectives
• Methods
• Justification for guideline question 1 recommendations
• Summary recommendations for guideline question 1
  • Recommendation 1: Doxy-PEP for GBMSM and TGW
  • Recommendation 2: Counselling on risks for shared decision making
• Contact us for full guidance

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/evidence 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. The 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 arising in professional practice and are not intended as a substitute for clinical judgment in consideration of individual circumstances and available resources.

Executive summary

Background

Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Treponema pallidum (TP; syphilis) are bacterial sexually transmitted infections (STI) that are a significant public health concern in Canada. CT, NG and TP disproportionately impact certain groups and communities, such as GBMSM (gay, bisexual and other men who have sex have men) and TGW (transgender women). In recent years, rates of these infections have been trending upwards in Canada despite numerous public health interventions. Factors that may be contributing to these observed increases include: a true rise in incidence; the use of improved diagnostic methods; and more effective contact tracing and case-finding.

Rationale for the guidelines

In the context of strong evidence for the prophylactic use of antiviral agents to prevent HIV, there is interest among health professionals and population disproportionately impacted by these infections for biomedical strategies for the prevention of CT, NG and TP. Evidence is emerging regarding the benefits and harms of prophylactic use of the antibiotic doxycycline for these infections, as pre-exposure prophylaxis (Doxy-PrEP) or post-exposure prophylaxis (Doxy-PEP). Importantly, the prevention and management of these infections occur within a broader context of antimicrobial use (AMU) and antimicrobial resistance (AMR). There is no current global consensus on the use of Doxy-PEP or Doxy-PrEP, prompting PHAC and the NAC-STBBI to prioritize the development of a Canadian recommendation in September 2023.

Objectives

The objectives of this work were to assess the following review questions to formulate recommendation(s) on the use of prophylactic doxycycline for the prevention of bacterial STI (CT, NG, TP):

1. What is the effectiveness of Doxy-PrEP and Doxy-PEP for the prevention of STI (Chlamydia trachomatis, Neisseria gonorrhoeae and Treponema pallidum [syphilis]) among people who are disproportionately affected by or deemed to be at high risk for STI as compared to no treatment, placebo, usual care, or any other intervention?
2. What are the possible antimicrobial resistance (AMR) consequences of the use of Doxy-PEP and Doxy-PrEP for the prevention of bacterial STI?

Methods

The recommendations were developed following the methods outlined in the 2014 "WHO handbook for guideline development" for STI experts, clinicians, researchers, and program managers. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology was applied to determine the certainty of evidence and strength of the recommendations. The STBBI Secretariat at PHAC initiated a scoping exercise, including an environmental scan, evidence review, and evidence synthesis. A working group comprised of NAC-STBBI members, and subject matter experts (PHAC and external) was formed at the beginning of the project to undertake this work.

An environmental scan was conducted to identify existing guidelines from national, international and sub-national (i.e., provincial, state or local) public health organizations; seven guidelines were identified and assessed. The quality of these guidelines was assessed using the Appraisal of Guidelines Research and Evaluation (AGREE) II instrument. Additionally, PROGRESS-Plus equity factors were identified in the guidelines to assess the range of social determinants and factors that contribute to health equity.

Broad research questions were developed for the evidence review in consultation with the working group. The key questions were approved with population, intervention, comparator and outcomes (PICO) elements by the NAC-STBBI and the working group. Ten guideline questions were prepared and four were prioritized for this phase of guideline development.

The four questions are:

1. Should Doxy-PEP or standard care be used in cisgender GBMSM TGW at risk of CT, NG or TP infection?
2. Should Doxy-PEP or standard care be used for sexually active adolescents and adults at risk of CT, NG or TP infection? [Forthcoming]
3. Should Doxy-PrEP or standard care be used in cisgender GBMSM and TGW at risk of CT, NG or TP infection? [Forthcoming]
4. Should Doxy-PrEP or standard care be used in sexually active adolescents and adults at risk of CT, NG or TP infection? [Forthcoming]

The population eligibility criteria were: cisgender GBMSM and TGW; sexually active adolescents and adults; cisgender heterosexual men; cisgender women; transgender men; all individuals assigned female at birth; individuals < 25 years of age. The intervention eligibility criteria were Doxy-PEP (200 mg within 72 hrs of condomless sex) and Doxy-PrEP (100 mg daily). The comparators included: standard care; consistent condom use; and STI screening and treatment per existing guidelines. Outcomes of interest were: STI incidence; STI-associated morbidity (including, for individuals assigned female at birth, infertility, pelvic inflammatory disease); total antimicrobial use (AMU); impact on microbiome; impact on AMR for target and non-target organisms; STI transmission; and quality of life. Multiple databases (PubMed, Embase, EBM Reviews, MedRxiv and ClinicalTrials.gov database) were searched using search strategies for any relevant publications up to September 15, 2023. Additional studies were identified by members of the working group up to September 30, 2024 and were included as appropriate.

A survey was conducted among stakeholders to assess the clarity of the recommendations for guideline question 1 and the feasibility of their implementation, including identifying any perceived barriers or facilitators. This feedback was presented to the working group before the recommendations were finalized.

Conflicts of interest were managed according to PHAC guidelines. At the beginning of each NAC-STBBI and working group meeting, the members disclosed their conflict of interests, if any. Some members of the group were selected due to their ongoing research on the topic and associated expertise. To manage any perceived conflict arising from these activities, those members were precluded from participating in discussions that examined the quality of their own work. After analysing each declaration of interest, it was concluded that no conflicts were identified by the working group and NAC-STBBI members that would prevent them from participating in the discussion and voting on the committee recommendations.

Justification for guideline question 1 recommendations

Findings from 4 clinical studies that evaluated the efficacy of Doxy-PEP were considered. Clinical studies among cisgender GBMSM and TGW, including those taking HIV pre-exposure prophylaxis (HIV PrEP) and those living with HIV, have found Doxy-PEP to be efficacious over the short term (12-18 months) for preventing CT, TP, and, in some studies, NG infections. For CT and NG, findings varied between studies and by anatomical site of infection. Doxy-PEP users experienced large reductions in incident early TP infections. In these studies, Doxy-PEP was administered as a 200 mg oral dose, ingested between 24 and 72 hours following condomless sex. Doxy-PEP may have some benefits in reducing the risk of NG, but this benefit is expected to be lower than for CT or TP due to higher rates of tetracycline resistance in NG at baseline in Canada and globally. The durability of any benefit for NG will be highly dependent on the evolution of resistant strains. Widespread Doxy-PEP use among cisgender GBMSM and TGW may favour the spread of other AMR, multidrug-resistant (MDR) and extensively drug-resistant (XDR) pathogens. Evidence indicates that use of tetracycline-class antimicrobials, such as doxycycline, creates AMR selection pressure. Drug-resistant pathogens with tetracycline co-resistance disproportionately affect these populations (e.g., XDR Shigella, MDR Neisseria gonorrhoeae, Mycoplasma genitalium, Staphylococcus aureus).

The overall certainty of evidence of effects is moderate (based on only the evidence for effectiveness; appraisal of AMR evidence has not yet been completed). However, in considering related evidence for and understanding of the development of antimicrobial resistance and antimicrobial stewardship principles, as well as the lack of evidence on patient values and preferences, resources use/cost-effectiveness, feasibility in Canadian context and mixed evidence on acceptability, the working group members selected the type of recommendation as a conditional recommendation for the intervention. The votes were divided as strong recommendation for (1 vote), conditional recommendation for (4 votes) and conditional recommendation against (2 votes) Doxy-PEP use for cisgender gbMSM and TGW at risk of CT, NG or TP infection. During the June 2025 NAC-STBBI teleconference, all present members voted to approve the conditional recommendations for Doxy-PEP use for cisgender GBMSM and TGW at risk of CT, NG or TP infection. Thus, the majority decision proceeds with "suggest".

In conclusion, the working group acknowledged the effectiveness of Doxy-PEP in preventing the acquisition of STI; however, concerns were raised about the short follow-up interval for currently available evidence and the uncertainty about the long-term benefits and harms from the intervention. The potential to accelerate AMR and MDR in target and non-target organisms remains a potential factor requiring ongoing monitoring and further assessment as new evidence becomes available. When examining equity factors for GBMSM and TGW, the working group determined that the use of Doxy-PEP has the potential to ameliorate disparities in rates of STI that disproportionately affect these populations. At the same time, the potential AMR harms of Doxy-PEP use could exacerbate AMR inequities (e.g. in AMR/MDR NG). Ultimately, when the working group considered these factors, it was determined that on balance, the known benefits of the intervention currently outweigh the potential harms, supporting the intervention.

Summary recommendations for guideline question 1

There are two recommendations related to the use of doxycycline prophylaxis for bacterial sexually transmitted infections (STI) prophylaxis in cisgender GBMSM and TGW. Recommendation 1 focuses on offering Doxy-PEP and recommendation 2 focuses on counselling. Remarks are provided for healthcare providers to explain the recommendation and describe any relevant considerations.

Recommendation 1: Doxycycline post-exposure prophylaxis for cisgender gay, bisexual and other men who have sex with men (GBMSM), and transgender women (TGW)

Recommendation 2: Counselling on risks for shared decision making

Contact us for full guidance

For the complete guidance on our recommendations on the use of prophylactic doxycycline for the prevention of bacterial STI (chlamydia, gonorrhea, syphilis), contact us at sti.secretariat-its@phac-aspc.gc.ca.