BACKGROUND: Canada has experienced rising rates of bacterial sexually transmitted infections (STIs)-notably syphilis, chlamydia, and gonorrhea-over the past 2 decades, especially among gay, bisexual, and other men who have sex with men. Doxycycline pre- and postexposure prophylaxis has emerged as a potential prevention strategy. However, concerns about antimicrobial resistance have prompted further investigation.
METHODS: We conducted a systematic review of English-language studies (2013-2023) using PubMed, Embase, Cochrane, and MedRxiv. We included randomized controlled trials, cohort, case-control, ecological studies, and systematic reviews that reported on prolonged or recurrent doxycycline use for any indication across all populations. Data were summarized descriptively due to heterogeneity, and risk of bias and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) assessments were conducted to rate the level of evidence.
RESULTS: Sixteen studies across 17 publications met the inclusion criteria. Included studies comprised 2 systematic reviews, 8 randomized controlled trials, 3 cohort studies, 2 cross-sectional studies, and 1 modeling study. Seven studies assessed tetracycline/doxycycline resistance in STI pathogens and 12 focused on non-STI organisms. Findings were mixed, with some studies reporting increased resistance, others minimal or no change. Neisseria gonorrhoeae showed high baseline doxycycline resistance. Evidence on resistance in skin and gut flora was limited and inconsistent, and no clear pattern of co-resistance to other antimicrobials was found. Overall, the quality of evidence was low to very low.
CONCLUSION: Evidence on antimicrobial resistance risks from doxycycline pre- and postexposure prophylaxis published up to 2023 was limited and uncertain. Findings are inconsistent and underpowered, and emerging evidence could change these conclusions.
